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Heart retransplant is a treatment option for some patients with graft failure. With heart donor short-age, it is important to assess candidates carefully for cardiac retransplant. An adult patient had a successful urgent heart retransplant due to severe toxic cardiomyopathy (anthracycline-induced) after posttransplant lymphoproliferative disease that was a diffuse large B-cell lymphoma.

Background: An acute increase in blood pressure is associated with the occurrence of premature ventricular complexes (PVCs)., Objective: We aimed to study the timing of these PVCs with respect to afterload-induced changes in myocardial deformation in a controlled, preclinically relevant, novel closed-chest pig model., Methods: An acute left ventricular (LV) afterload challenge was induced by partial balloon inflation in the descending aorta, lasting 5-10 heartbeats (8 pigs; 396 inflations)., Results: Balloon inflation enhanced the reflected wave (augmentation index 30% ± 8% vs 59% ± 6%; P < .001), increasing systolic central blood pressure by 35% ± 4%. This challenge resulted in a more abrupt LV pressure decline, which was delayed beyond ventricular repolarization (rate of pressure decline 0.16 ± 0.01 mm Hg/s vs 0.27 ± 0.04 mm Hg/ms; P < .001 and interval T-wave to peak pressure 1 ± 12 ms vs 36 ± 9 ms; P = .008), during which the velocity of myocardial shortening at the basal septum increased abruptly (ie, postsystolic shortening) (peak strain rate -0.6 ± 0.5 s(-1) vs -2.5 ± 0.8 s(-1); P < .001). It is exactly at this time of LV pressure decline, with increased postsystolic shortening, and not at peak pressure, that PVCs occur (22% of inflations). These PVCs preferentially occurred at the basal and apical segments. In the same regions, monophasic action potentials demonstrated the appearance of delayed afterdepolarization-like transient depolarizations as origin of PVCs., Conclusion: An acute blood pressure increase results in a more abrupt LV pressure decline, which is delayed after ventricular repolarization. This has a profound effect on myocardial mechanics with enhanced postsystolic shortening. Coincidence with induced transient depolarizations and PVCs provides support for the mechanoelectrical origin of pressure-induced premature beats., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Relative apical sparing of longitudinal systolic strain (LSsys) with preserved LSsys at apical and significantly reduced LSsys at mid/basal segments is a typical echocardiographic feature in AL amyloidosis patients with cardiac involvement. The present study aims to evaluate the change of this typical feature over time by serial echocardiography and its impact on outcome in AL amyloidosis patients with cardiac involvement. Echocardiography was performed in 24 consecutive patients with biopsy-proven AL amyloidosis (mean age 64 ± 9 years; 50% male) at baseline and during a median of 257 (quartiles 103-651) days follow-up. Global and segmental LSsys were assessed by two-dimensional speckle-tracking-imaging in septal and lateral segments of the left ventricle (LV) from the apical 4-chamber view. Sixteen (67%) patients died during a median follow-up of 487 days (quartiles 223-872). LV global and segmental LSsys remained unchanged over time in survivors (all P > 0.05), while LV global, septal-apical and lateral-apical LSsys significantly decreased in non-survivors. A decrease in lateral-apical LSsys > 3.0% independently predicted a fivefold increased all-cause mortality risk after adjustment for age, gender, NYHA class, and treatment strategies. Further, baseline serum NT-proBNP, serum albumin decrease during follow-up, baseline septal apical-to-basal LSsys ratio and lateral-apical LSsys decrease during follow-up remained independently predictive of increased all-cause mortality risk. Serial monitoring of serological and echocardiographic parameters is valuable to predict outcome in AL amyloidosis patients with cardiac involvement. The best follow-up parameter to predict risk for imminent death is a decrease of longitudinal systolic strain at the lateral apical segment.

Objectives: Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA), we hypothesized that speckle-tracking-imaging (STI) derived longitudinal early diastolic strain rate (LSRdias) could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%)., Background: Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys) assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients., Methods: Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years). Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views., Results: Nineteen (46%) out of 41 CA patients died during a median of 16 months (quartiles 5-35 months) follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6 ± 2 vs. 8 ± 3 mm), global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p < 0.05). NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.17-3.26, P = 0.010), global LSRdias (HR = 7.30, 95% CI 2.08-25.65, P = 0.002), and E/LSRdias (HR = 2.98, 95% CI 1.54-5.79, P = 0.001) remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S-1 (sensitivity 68%, specificity 67%). Global LSRdias < 0.85 S-1 predicted a 4-fold increased mortality in CA patients with preserved LVEF., Conclusions: STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF.

Background: Neurological complications after cardiac surgery have a profound impact on postoperative survival and quality of life. The increasing importance of strategies designed to improve neurological outcomes mirrors the growing risk burden of the contemporary cardiac surgical population. Remote ischemic preconditioning (RIPC) reduces adverse sequelae of ischemia in vulnerable organs by subjecting tissues with high ischemic tolerance to brief periods of hypoperfusion. This trial will evaluate the neuroprotective effect of RIPC in the cardiac surgical arena, by employing magnetic resonance imaging (MRI) and neurocognitive testing., Methods: Patients scheduled for elective coronary artery bypass grafting with the use of cardiopulmonary bypass will be screened for the study. Eligible patients will be randomized to undergo either a validated RIPC protocol or a sham procedure. The RIPC will be induced by inflation of a blood pressure cuff to 200 mmHg for 5 minutes, followed by a 5-minute reperfusion period. Three sequences of interchanging cuff inflations and deflations will be employed. Neurocognitive testing and MRI imaging will be performed preoperatively and on postoperative day 7. Paired pre- and postoperative neurocognitive and neuroimaging data will then be compared. The primary composite outcome measure will consist of new ischemic lesions on brain MRI, postprocedural impairment in brain connectivity on resting-state functional MRI (rs-fMRI), and significant new declines in neurocognitive performance. The secondary endpoint measures will be the individual components of the primary endpoint measures, expressed as continuous variables, troponin T release on postoperative day 1 and the incidence of major adverse cardiovascular events at 3 months postoperatively. Major adverse cardiovascular events, including accumulating cardiovascular mortality, stroke, nonfatal myocardial infarction, and rehospitalization for ischemia, will form a composite endpoint measure., Discussion: This trial will aim to assess whether RIPC in patients subjected to surgical myocardial revascularization employing cardiopulmonary bypass initiates a neuroprotective response. Should the results of this trial indicate that RIPC is effective in reducing the incidence of adverse neurological events in patients undergoing coronary artery bypass grafting, it could impact on the current standard of care., Trial Registration: ClinicalTrials.gov NCT02177981.

Several recent technical advances in cardiac ultrasound allow data to be acquired at a very high frame rate. Retrospective gating, plane/diverging wave imaging, and multiline transmit imaging all improve the temporal resolution of the conventional ultrasound system. The main drawback of such high frame rate data acquisition is that it typically has reduced image quality. However, for given clinical applications, the acquisition of temporally-resolved data might outweigh the reduction in image quality. It is the aim of this paper to provide an overview of the technical principles behind these new ultrasound imaging modalities, to review the current evidence of their potential clinical added value, and to forecast how they might influence daily clinical practice., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Chronic atrial volume overload and atrial fibrillation (AF) induce structural changes within atrial myocardium. The aim of this study was to evaluate the effect of adverse cellular remodelling on echocardiographic strain rate (SR) deformation indices of atrial contractile, conduit and reservoir functions., Methods: Forty-four consecutive patients with organic mitral regurgitation were analysed. Twenty-eight patients had long-standing persistent AF (AF group), while 16 were in normal sinus rhythm (NSR group). Left atrial (LA) samples were harvested from all the patients for histological analysis. Postoperative echocardiographic data acquisition was performed exclusively during organized atrial electrical activity in order to assess the contractile reserve of patients from both groups., Results: Fibrotic atria had inferior conduit (SR-E: r = -0.36, P = 0.017), reservoir (SR-S: r = -0.31, P = 0.041) and contractile functions (SR-A: r = -0.33, P = 0.027). Analogously, atria with greater apoptotic burdens showed a negative correlation with multiple indices of left atrial functions (SR-E: r = -0.38, P = 0.010; SR-S: r = -0.33, P = 0.028; SR-A: r = -0.28, P = 0.067). The efficiency of atrial contractility was significantly reduced among AF-group patients after conversion to sinus rhythm, when compared with patients in the NSR group (LA active emptying fraction: 20 ± 12 vs 30 ± 10%, P = 0.004; SR-A: 1.1 ± 1.0 vs 2.8 ± 1.9 s(-1), P < 0.001). Superior strain-rate indices of atrial conduit and reservoir functions were noted in the NSR group (SR-E: 3.5 ± 2.3 vs 1.3 ± 1.0 s(-1), P < 0.001; LA expansion index: 86 ± 31 vs 60 ± 42%, P = 0.004). Fibrosis was evident in 7.2 [3.3;9.4]% of the LA tissue sample in the AF group, while it accounted for 3.4 [1.2;8.1]% of atrial tissue in the NSR group (P = 0.054). Apoptosis was documented in 13 (46%) patients in the AF group, whereas none of the patients in the NSR group exhibited signs of programmed cell death (P = 0.001). Myocyte degeneration was more prevalent in the AF group (odds ratio: 7.0, 95% confidence interval: 1.3-36.7, P = 0.021). Age showed a positive correlation with worsening degrees of atrial fibrosis and apoptosis (r = 0.41, P = 0.006; r = 0.49, P = 0.001, respectively). Multiple regression analysis identified SR-S (β = -1.263, P = 0.036) and age (β = 0.144, P = 0.057) as independent predictors of fibrosis. Independent determinants of apoptosis were preoperative AF (β = 4.539, P = 0.007), age (β = 0.188, P = 0.009) and SR-S (β = -1.780, P = 0.002)., Conclusions: Atria exhibiting greater fibrotic and apoptotic burdens had impaired conduit, reservoir and contractile function, as evaluated by deformation imaging. Among patients with chronic LA volume overload, exposure to long-standing persistent AF induced more pronounced degrees of adverse atrial cellular remodelling. Strain-rate descriptors of atrial reservoir function harboured potential to predict atrial fibrosis and apoptosis., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Image segmentation is an ubiquitous task in medical image analysis, which is required to estimate morphological or functional properties of given anatomical targets. While automatic processing is highly desirable, image segmentation remains to date a supervised process in daily clinical practice. Indeed, challenging data often requires user interaction to capture the required level of anatomical detail. To optimize the analysis of 3D images, the user should be able to efficiently interact with the result of any segmentation algorithm to correct any possible disagreement. Building on a previously developed real-time 3D segmentation algorithm, we propose in the present work an extension towards an interactive application where user information can be used online to steer the segmentation result. This enables a synergistic collaboration between the operator and the underlying segmentation algorithm, thus contributing to higher segmentation accuracy, while keeping total analysis time competitive. To this end, we formalize the user interaction paradigm using a geometrical approach, where the user input is mapped to a non-cartesian space while this information is used to drive the boundary towards the position provided by the user. Additionally, we propose a shape regularization term which improves the interaction with the segmented surface, thereby making the interactive segmentation process less cumbersome. The resulting algorithm offers competitive performance both in terms of segmentation accuracy, as well as in terms of total analysis time. This contributes to a more efficient use of the existing segmentation tools in daily clinical practice. Furthermore, it compares favorably to state-of-the-art interactive segmentation software based on a 3D livewire-based algorithm., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Differentiation of cardiac amyloidosis (CA) from other causes of concentric left ventricular hypertrophy remains a clinical challenge, especially in patients with preserved ejection fraction at the early disease stages., Methods and Results: Consecutive hypertrophic patients with CA, isolated arterial hypertension, Fabry disease, and Friedreich ataxia (n=25 per group) were investigated; 25 healthy volunteers served as a control group. Standard echocardiography was performed, and segmental longitudinal peak systolic strain (LSsys) in the septum was assessed by 2-dimensional speckle tracking imaging. Indices of left ventricular hypertrophy and ejection fraction were similar among all patient groups. Deceleration time of early filling was significantly lower in patients with CA (147±46 milliseconds) compared with those with isolated arterial hypertension, Fabry disease, or control subjects (all P<0.0125). Septal basal LSsys (-6±2%) was significantly lower in patients with CA compared with those with isolated arterial hypertension (-14±6%), Fabry disease (-12±5%), Friedreich ataxia (-16±2%), or control subjects (-17±3%; all P<0.001), whereas septal apical LSsys was similar among all patient groups and control subjects (all P>0.05). A data-driven cutoff value for the ratio of septal apical to basal LSsys ratio >2.1 differentiated CA from other causes of left ventricular hypertrophy (sensitivity, 88%; specificity, 85%; positive predictive value, 67%; negative predictive value, 96%). The prevalence of septal apical to basal LSsys ratio >2.1 plus deceleration time of early filling <200 milliseconds was 88% in CA but 0% in all other groups., Conclusions: A systolic septal longitudinal base-to-apex strain gradient (septal apical to basal LSsys ratio >2.1), combined with a shortened diastolic deceleration time of early filling (deceleration time of early filling <200 milliseconds), aids in differentiating CA from other causes of concentric left ventricular hypertrophy.

Objectives: The aim of this study was to explore the left ventricular (LV) deformation changes and the potential impact of deformation on outcome in patients with proven light-chain (AL) amyloidosis and LV hypertrophy., Background: Cardiac involvement in AL amyloidosis patients is associated with poor outcome. Detecting regional cardiac function by advanced non-invasive techniques might be favorable for predicting outcome., Methods: LV longitudinal, circumferential and radial peak systolic strains (Ssys) were assessed by speckle tracking imaging (STI) in 44 biopsy-proven systemic AL amyloidosis patients with LV hypertrophy (CA) and in 30 normal controls. Patients were divided into compensated (n = 18) and decompensated (n = 26) group based on clinical assessment and followed-up for a median period of 345 days., Results: Ejection fraction (EF) was preserved while longitudinal Ssys (LSsys) was significantly reduced in both compensated and decompensated groups. Survival was significantly reduced in decompensated group (35% vs. compensated 78%, P = 0.001). LSsys were similar in apical segments and significantly reduced in basal segments between two patient groups. LSsys at mid-segments were significantly reduced in all LV walls of decompensated group. Patients were further divided into 4 subgroups according to the presence or absence of reduced LSsys in no (normal), only basal (mild), basal and mid (intermediate) and all segments of the septum (severe). This staging revealed continuously worse prognosis in proportion to increasing number of segments with reduced LSsys (mortality: normal 14%, mild 27%, intermediate 67%, and severe 64%). Mid-septum LSsys<11% suggested a 4.8-fold mortality risk than mid-septum LSsys≥11%. Multivariate regression analysis showed NYHA class and mid-septum LSsys were independent predictors for survival., Conclusions: Reduced deformation at mid-septum is associated with worse prognosis in systemic amyloidosis patients with LV hypertrophy.

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.

Aims: Pronounced trabeculation is presented in both left ventricular non-compaction (LVNC) and dilated cardiomyopathy (DCM), which sometimes makes the differentiation difficult. We hypothesized that echocardiographic deformation analysis would help to differentiate these two cardiomyopathies., Methods and Results: We investigated 15 patients with LVNC (9 males; 42 ± 9 years), 15 age- and gender-matched DCM patients, and 15 healthy controls. The echocardiographic diagnosis of LVNC was confirmed by magnetic resonance imaging. In all subjects standard echocardiography and tissue Doppler imaging (TDI) to study regional LV deformation were carried out. No statistical difference was observed in standard echocardiographic parameters between LVNC and DCM patients. Compared with controls, both patient groups showed significantly reduced annular displacements (septal: controls 14 ± 2 mm vs. DCM 6 ± 3 mm vs. LVNC 7 ± 3 mm) and reduced strain values of the LV segments. A characteristic deformation pattern with significantly higher values in the LV base compared with the apex was observed in patients with LVNC by deformation measurements with TDI. This gradient was found particularly in the lateral and inferior wall but spared the anteroseptal wall; non-compaction was not found in basal segments throughout the ventricle and also spared the anteroseptal midventricular wall. In DCM the strain and strain rate values were homogeneously reduced in all LV segments., Conclusion: A special regional deformation pattern (preserved deformation in basal segments of LVNC) seems to be of major diagnostic help for the definite differential diagnosis of LVNC and DCM.

Background: Adults with sickle cell disease (SCD) and pulmonary hypertension have high mortality but death in SCD children with pulmonary hypertension is rare. The authors hypothesised that pulmonary hypertension in SCD children may be secondary to anaemia-induced high cardiac output rather than pulmonary vascular disease., Methods: Two independent, validated techniques were used to estimate pulmonary vascular resistance (PVR) in 50 SCD children and 50 matched controls. Tricuspid regurgitant jet velocity (TRV) and right ventricular outflow tract velocity time integral were measured using Doppler echocardiography; PVR was calculated from their ratio. Acetylene rebreathing technique using respiratory mass spectrometry was also performed to calculate pulmonary blood flow and stroke index, an estimate of PVR., Results: TRV was higher in SCD children compared with controls (2.28 vs 2.14 m/s, p=0.02). Fifteen of 34 (44%) children with haemoglobin of the SS genotype (HbSS) versus 1/16 (6%) children with haemoglobin of the SC genotype (HbSC) had pulmonary hypertension (TRV≥2.5 m/s) (p=0.009). Right ventricular stroke volume was higher (p<0.05) and Doppler PVR lower (1.20 (0.19) vs 1.31 (0.20) Wood units, p=0.04) in SCD children with pulmonary hypertension compared with controls. Qpeff and stroke index were higher in SCD children compared with controls (p<0.001 for both) and correlated with anaemia (p<0.001) and TRV (p=0.03). There was no correlation between TRV and history of asthma or acute chest syndrome., Conclusions: Pulmonary hypertension due to raised cardiac output is common in HbSS SCD children and is associated with normal PVR. PVR should be measured before therapy with agents such as sildenafil or bosentan is contemplated.

Echocardiography has a leading role in the routine assessment and diagnosis of hypertrophic ventricles. However, the use of M-mode echocardiography and measurement of global left ventricular function may be misleading. Traditionally, systolic function was thought to be preserved in patients with hypertrophic myopathies until the late stages of the disease, and hypertrophic myopathies were thought to affect the myocardium more diffusely than ischemic heart disease. Ultrasound deformation imaging, either by Doppler myocardial imaging or speckle tracking, provides more-sensitive detection of regional myocardial motion and deformation than standard echocardiography. Basic and clinical studies that apply these techniques have revealed early, often subclinical impairment in systolic function. This information allows the detection and treatment of myocardial dysfunction at an early stage, which is of high clinical importance. Physiological hypertrophic remodeling seen in athletes differs from pathological myocardial hypertrophy, which can be caused by compensatory reactive hypertrophy owing to pressure overload in patients with aortic stenosis or hypertension, as well as amyloidosis, Fabry disease or Friedreich ataxia. Each of the etiologies associated with hypertrophy demonstrate distinct regional changes in myocardial deformation, which allows identification of the underlying processes, and will improve the assessment and follow-up of patients with hypertrophic myopathies.

Background: Although cardiac resynchronization therapy (CRT) is well established as an adjunctive heart failure treatment, a 30% rate of nonresponders poses a challenge to improve the detection of potential responders prior to device implantation. A previously proposed mechanism-based approach to patient selection suggests in part that the septal flash is a sign of intraventricular dyssynchrony, which is predictive of CRT responsiveness., Methods: In this pilot study, data from 5 consecutive patients (2 women and 3 men; mean + or - SD age, 62 + or - 9 years) referred for CRT device implantation via a minithoracotomy were analyzed. Intraoperative transthoracic and/or transesophageal echocardiography data, as well as Doppler myocardial imaging data, were acquired before and after CRT device activation. The septal flash was defined as an early ventricular inward and outward septal motion within the isovolumic contraction period and was imaged with grayscale imaging or tissue Doppler color M-mode. Reverse remodeling was defined as a reduction in the left ventricular end-systolic volume (LVESV) of > or =10%. The right atrial and right ventricular leads were placed transvenously, and the LV screw-in lead was positioned epicardially on the lateral wall., Results: The septal flash was detected preoperatively in all patients and resolved immediately after the onset of biventricular pacing. Immediately following pacemaker activation, we measured a significant reduction in the LVESV (248 + or - 99 mL versus 190 + or - 100 mL, P = .01) and an increase in the ejection fraction (19% + or - 5% versus 28% + or - 5%, P = .01) in all patients. Likewise, a significant increase in the postactivation dP/dt (rate of LV pressure change) measured noninvasively from the mitral regurgitation trace was noted in all patients (298.6 + or - 58.0 mm Hg/s versus 601.7 + or - 111.2 mm Hg/s, P = .001)., Conclusion: The preoperative presence of the septal flash is a valid predictor of the response to CRT. Immediately after CRT device activation, the septal flash disappears, and LV reverse remodeling and an increase in contractility are observed.

ESH/ECS guidelines for diagnostics and treatment of arterial hypertension 2007 is a basic paper for all physicians who treat hypertensive patients. Since publishing, this article has been the most cited medical paper. According to ESH/ECS guidelines some local peculiarities in each country should be considered when diagnosing and treating hypertensive patients. Practical recommendations of the Croatian working group for the diagnostics and treatment of hypertension are in agreement with ESH/ECS guidelines. However, few additional issues are added and further discussed in this paper (hypertensive crisis, treatment of hypertension in patients undergoing dialysis and in renal transplanted patients, role of family physicians, role of nurse). We believe that this paper will contribute better control of hypertension in Croatia. All medical societies and institutions that took part in writing this document, have to consider this paper as an official statement.

Aim: To determine if Color Doppler myocardial imaging could provide evidence of diastolic dysfunction in patients with hypertension whose pulse-wave Doppler parameters were normal., Method: The study included 33 patients (mean age 48+/-7.3 years) and a control group of 13 sex- and age-matched healthy individuals. Patients were divided into two groups according to mean blood pressure (BP) values during 24-hour blood pressure monitoring while under antihypertensive therapy: those with uncontrolled hypertension (n=22) and those with controlled hypertension (n=11). All study participants underwent complete standard echocardiography (2D, M-mode, pulsed and continuous Doppler) and a Color Doppler myocardial imaging study., Results: Conventional Doppler parameters indicated relaxation disturbances in patients with uncontrolled hypertension, but were within a normal range in patients with controlled hypertension at baseline and follow-up. Parameters of global diastolic function measured by Color Doppler myocardial imaging revealed that E'/A', the ratio between E'-wave (early filling phase) and A'-wave (late diastolic wave due to atrial contraction), was <1 in 57% of segments at baseline in patients with uncontrolled hypertension, and did not significantly change at follow-up. In patients with controlled hypertension, E'/A'<1 was noted in 4.7% of segments at baseline and in 28.6% of segments at follow-up., Conclusion: Regional diastolic dysfunction measured by Color Doppler myocardial imaging was the first sign of myocardial dysfunction due to arterial hypertension, while the parameters of global diastolic dysfunction measured by conventional Doppler and Color Doppler myocardial imaging were still normal. Furthermore, in patients with uncontrolled hypertension with manifested global diastolic dysfunction, there was a change in late diastolic parameters. Our results point to a potentially important role of Color Doppler myocardial imaging in diagnosing hypertensive heart disease as well as in follow-up of treatment.

Predictive tests assisting in selection of breast cancer patients for endocrine therapy have been reviewed. Information gained from histologic sections, such as degree of the tumor differentiation, degree of elastosis, Barr-body count and the DNA content, are valuable predictors of prognosis and response to endocrine therapy. The length of time between mastectomy and recurrence of metastasis is an important factor in predicting response to ablative endocrine surgery. The presence of various enzymes in the tumor tissue, blood groups, immunologic competence, altered metabolism of tryptophan, urinary excretion of steroids and in vitro hormonal responsiveness of the tumor tissue have not been widely used as predictors of tumor response to endocrine therapy. The determination of hormone receptors in primary or metastatic breast tumors is at present the most reliable test in selecting breast cancer patients for endocrine therapy. Future developments in hormone receptor assay may provide a means of tailoring endocrine therapy to the individual patient.

Hormone-dependent tumors have a decreased requirement for growth stimulating hormones compared with the normal tissues from which the tumors originate. This property of hormone-dependent tumors is due to an inappropriate expression of hormone receptors in and by cancer cells making these cells highly sensitive to growth stimulating effects of hormones, and a variety of growth factors, compared with their normal counterparts. In the early stages of tumor development, the ectopic receptors for hormones are inappropriately expressed in cancer cells. The expression of multiple ectopic receptors for hormones and growth factors confers an apparent autonomy on cancer cells. In some instances, cancer cells have been found to exhibit hormonal sensitivity and hormone receptor content as do their normal counterparts at earlier developmental stages.

When cultured murine lymphomas were retransplanted into syngeneic hosts, the quantitative representation of H-2 antigens and Moloney leukemia virus-determined cell-surface antigens tended to revert to the antigenic pattern characteristic of the corresponding lines propagated in vivo. In some instances, a complete reversion of both the virus-specific and H-2 antigens was observed after a single passage of cultured lymphoma cells in syngeneic hosts.

The clinical profile of aminoglutethimide (AG), an amino derivative of the hypnotic agent glutethimide, is described. AG suppresses estrogen formation in postmenopausal women by its inhibitory effect on steroid synthesis in the adrenal glands as well as in the peripheral tissues. The results of treatment of 959 breast cancer patients by AG and glucocorticoids in several studies are reviewed. The treatment of these patients, who were not selected according to the hormonal receptor status in their tumors, resulted in about 30% objective responses. About 50% of the patients with estrogen receptor positive tumors responded with an objective regression. The favorable effect of medical adrenalectomy is comparable to that of hypophysectomy or surgical adrenalectomy; the advantage of medical adrenalectomy compared to ablative endocrine surgery is reversibility of the inhibitory effect on the production of adrenal hormones and estrogens after cessation of treatment. The AG-glucocorticoid regimen appears to exert a greater effect on skeletal metastases than tamoxifen. Patients who fail on tamoxifen and other endocrine regimens can still benefit from AG-glucocorticoid treatment. The value of medical adrenalectomy as adjuvant treatment is not yet known. At present, several agents with a selective effect on androgen-to-estrogen conversion in the peripheral tissues are under study. Their potential as inhibitors of the estrogen production in breast cancer patients is considerable.

A mouse cell line derived from bone marrow (JLS-V9) was infected in vitro with Moloney leukemia virus. After the cell-surface antigens specified by this virus appeared, cells were synchronized in mitosis by a short treatment with colcemid. The expression of H-2- and virus-determined surface antigens was monitored during one cell cycle by an indirect membrane-immunofluorescence test. The highest proportion of antigen-positive cells was found during the G1 period; the proportion dropped as the cells entered the S period, and remained low until they entered the G1 period of the next cycle. The H-2- and virus-determined surface antigens were temporally coexpressed.

The expression of H-2 and Moloney leukemia virus (MLV)-determined surface antigens of MLV-induced mouse lymphoma cells (YCAB) was studied during growth in vitro by indirect membrane immunofluorescence and complement-dependent, antibody-mediated cytotoxic sensitivity. In a growing cell population, the degree of antigenic expression was inversely related to the growth rate and cell volume. These findings suggest that the antigenic properties of YCAB cells are maximally expressed during the early interphase, presumably a part of the G1 period, and that the fast-growing cells pass relatively quickly through G1. The life cycle analysis of the same cells at varying intervals during the growth cycle revealed that the prolongation of population doubling time was mainly due to an extension of the G1 period, whereas the duration of S, G2, and mitosis was much less affected. The cell volume per se did not appreciably influence the expression of surface antigens. Populations of large cells were more rapidly growing, since they were in the late stage of their cycle.