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Cardiologists and oncologists are challenged to optimize safety and effectiveness of chemotherapy. The quest for therapeutic cancer cure is hampered by the risk of cardiotoxicity including potentially fatal clinical heart failure. Management of chemotherapy administration concordant with strategic baseline EF guideline recommendations for cumulative doxorubicin dose-related timing of accurate and precise radionuclide LVEF measurements, and recommendations for termination of therapy have been demonstrated in high-risk patients to change the natural history of heart failure associated with anthracycline cardiotoxicity.– Personalizing cardiooncologic care with specific chemotherapy regimens requires use of techniques and monitoring guidelines which have been proven effective by study of long term outcomes in high-risk patients who have abnormal baseline LVEF or those whose residual cancer risk requires consideration of ongoing chemotherapy. However, evidence of safe and effective management for timing and termination of chemotherapy by serial EF determinations without use of strategic baseline EF guidelines, use of other techniques such as echocardiographic EF and strain imaging, LV and RV volume indices, MIBG, biomarkers, and other novel markers remains undefined by prospective trials in high-risk patients receiving anthracycline and other types of chemotherapy. A potentially important set of novel risk markers of chemotherapy-induced heart failure includes measures of diastolic LV dysfunction which can precede systolic dysfunction in anthracycline and perhaps other chemotherapies and provide a more sensitive and specific predictor of long-term chemotherapy-induced heart failure. The importance of diastolic dysfunction and its progression to diastolic heart failure, now called ‘‘HFpEF’’ or ‘‘heart failure with preserved ejection fraction’’ in clinical cardiology, have been recognized for decades. Early studies identified a role for the negative inotropic and chronotropic therapies including the calcium channel blocker verapamil and beta blockers in the management of diastolic heart failure in hypertension or hypertrophic cardiomyopathy.– Radionuclide ventriculography identified a reduction in the diastolic peak filling rate and prolongation of the time to peak filling associated with HFpEF, and improvements in these dynamic filling characteristics and clinical heart failure with calcium and beta blockade therapy have been demonstrated.– Diastolic dysfunction was identified by Lee et al. with serial radionuclide angiography as an early marker of doxorubicin cardiotoxicity prior to reduction of LVEF in patients receiving doxorubicin. This observation was soon followed by reports of early diastolic dysfunction using Doppler echocardiography of LV filling dynamics during doxorubicin treatment. These observations suggested nearly three decades ago the potential to enhance the diagnostic and prognostic assessment of heart failure risk associated with progressive myocytolysis defined by serial endomyocardial biopsy during anthracycline Reprint requests: Ronald G. Schwartz, MD MS, Cardiology Division, Department of Medicine, University of Rochester Medical Center, Rochester; ronald_schwartz@urmc.rochester.edu J Nucl Cardiol 2016;23:833–6. 1071-3581/$34.00 Copyright 2015 American Society of Nuclear Cardiology.

Background Integrated bedside and sophisticated cardiac imaging techniques help characterize the discrepancy between myocardial injury and mechanic dysfunction in acute myocardial infarction. Case presentation A 57 year-old woman presented with sudden onset chest pain and ventricular fibrillation after hearing of her brother’s death. The electrocardiography indicated “anterior wall ST segment elevation myocardial infarction”. Coronary angiography ruled out obstructive lesion in the major coronary arteries, but revealed fibromuscular dysplasia of the distal left anterior descending artery. The ventriculography showed remarkable ventricular dilation, which affected much broader myocardium than the culprit vessel supplied. In a subsequent cardiac magnetic resonance study, delayed contrast (gadolinium) image revealed a focal left ventricular (LV) apical infarction. Her LV systolic function normalized within 1 week, except for a residual apical hypokinesis. She developed recurrent chest pain and LV dilation when she was laid off 9 months later. After supportive therapy, her symptoms improved and LV dysfunction normalized again. Conclusions “Tako-tsubo” syndrome can occur recurrently in the heart with pre-existing localized myocardial infarction. Its molecular mechanism and clinical significance warrants further investigation.

Cardiotoxicity is an important complication of cancer therapy. With a significant improvement in the overall survival and prognosis of patients undergoing cancer therapy, cardiovascular toxicity of cancer therapy has become an important public health issue. Several well-established as well as newer anticancer therapies such as anthracyclines, trastuzumab, and other HER2 receptor blockers, antimetabolites, alkylating agents, tyrosine kinase inhibitors, angiogenesis inhibitors, checkpoint inhibitors, and thoracic irradiation are associated with significant cardiotoxicity. Cardiovascular imaging employing radionuclide imaging, echocardiography, and magnetic resonance imaging is helpful in early detection of the cardiotoxicity and prevention of overt heart failure. These techniques also provide important tools for understanding the mechanism of cardiotoxicity of these modalities, which would help develop strategies for the prevention of cardiac morbidity and mortality related to the use of these agents. An understanding of the mechanism of the cardiotoxicity of cancer therapies can help prevent and treat their adverse cardiovascular consequences. Clinical implementation of algorithms based upon cardiac imaging and several non-imaging biomarkers can prevent cardiac morbidity and mortality associated with the use of cardiotoxic cancer therapies.

Why do clinicians continue to perform gated blood pool imaging when other methods are available to assess left ventricular (LV) ejection fraction (EF)? One reason is that blood pool scanning continues to be the method favored for serial LV EF evaluations to detect cardiotoxicity caused by anthracycline therapy for several cancers in adults, 1,2 and for Hodgkins disease in children. 3 Echocardiography is considered inadequate for this purpose, 3,4 cardiac CT delivers considerably higher radiation dose than would be desirable for serial evaluations, and cardiac MRI is not widely available. For evaluation of cardiotoxicity, simultaneous perfusion assessment is not required, because anthracyclines cause generalized myocyte failure throughout the myocardium in a uniform fashion, manifest as global hypokinesis. 5 Planar blood pool scans have the advantage of simplicity and enable reproducible EF values. 6 EF reproducibility to within 5% has been considered a minimal requirement due to observations that a drop of more than 5 EF points from rest to stress is a significant prognostic indicator, signaling a high likelihood of future adverse cardiac events. 7-9 Building on those technical foundations, most clinicians consider a drop of more than 5 EF points due to chemotherapy to be clinically significant, with an overall decline below LVEF of 50% to be of serious concern. 3,10 Many patients undergoing chemotherapy are followed for several years after baseline assessment of cardiac function. Due to recent advances in technology, in the current nuclear imaging environment this can present referring physicians with a dilemma. They may have a long history of interpreting the implications of changes in planar blood pool EF values for patients in general, and have serial measurements for their own individual patients. Now they are confronted with an increasing prevalence of imaging facilities that are incapable of performing planar blood pool imaging, but instead have solid state SPECT capability, of which the referring physicians are told are superior to planar cameras. How are they going to interpret new EF results, and how will they subsequently manage their patients, when they are no longer able to obtain planar blood pool EF measurements in patients for whom they have successive planar blood pool EF values determined over many years? In ‘‘Assessment of an Intermediate Reprojection Technique Transitioning from Planar to SPECT Radionuclide Ventriculography’’ in the current issue of the Journal, 11 O’Doherty et al report similar EF values obtained by reprojected SPECT blood pool tomograms when compared to data in the same patients who also had conventional planar blood pool acquisitions. Why would there be any question that a reprojected tomogram would produce different EF values than if planar data had been acquired instead? One reason is that the reconstruction process requires multiple choices from among several available options. True maximum likelihood estimation maximization (ML-EM) iterative reconstruction algorithms involve lengthy computations and are not commercially available 12 ; rather, accelerated

Dysfunction of the right ventricle (RV) can occur in several aspects of cardiovascular disease (CVD) such as pulmonary hypertension (PH), congenital heart disease, left-sided heart failure (HF), coronary artery disease, and RV myocardial infarction, or valvular heart disease. The independent prognostic value of RV function is most strongly established for HF and PH, but the role of the RV in CVD has thus far remained relatively neglected. Cardiac magnetic resonance (CMR) imaging is often considered the gold standard in RV function assessment because it provides high-resolution images of the RV cavity and myocardium. This allows for RV measurements without the need for geometric assumptions required with 2D echo-based techniques or planar radionuclide ventriculography (PRNV). An important advantage of CMR is the high spatial and temporal resolution of the images, while the lack of fully automated processing introduces operator dependence and therefore increases interand intra-observer variability. In this issue of the Journal of Nuclear Cardiology , Dercle et al report on the use of three algorithms for the assessment of RV function using gated blood pool SPECT (GBPS) and compare the results of these methods with CMR-derived values. GBPS offers several potential advantages over other imaging modalities for RV analysis; notably, the acquisition is fast and technically simple, the resulting images are fully threedimensional (3D, or rather 4D if one includes gating), and processing is comparatively operator-independent due to the availability of automatic or semi-automated analysis algorithms. The ability to automatically and reproducibly analyze 3D images of the RV is important given its complex geometry, characterized by a triangular shape in horizontal long-axis view and a crescent shape in short-axis view. While the left ventricle (LV) can adequately be modeled by an ellipsoid clipped by a singular plane that represents both the mitral and aortic valves, RV segmentation is further complicated by the fact that the tricuspid and pulmonary valves are not coplanar and are separated by the ventriculoinfundibular fold, as opposed to the fibrous continuity of the LV valves. Given the anatomy of the RV, the main drawbacks of GBPS are the absence of tissue differentiation and the low resolution of the images (typically in the order of 6 mm/voxel, isotropically). This low resolution in turn leads to several challenges: partial volume effect renders segmentation error-prone when the apical portion of the RV cavity contracts, count spillover complicates visualization and segmentation of the interventricular septum, and the lack of fine anatomical detail virtually eliminates the ability to accurately locate the pulmonary valve. These effects are often exacerbated by the use of a low cutoff (smooth) reconstruction filter, a common occurrence in laboratories that primarily perform myocardial perfusion studies where such filter settings may be advisable and are generally the default for cardiac SPECT. The results described by Dercle et al confirm the impact of such challenges: while RV end-diastolic volumes (EDV) correlate moderately to well with CMR Reprint requests: Serge D. Van Kriekinge PhD, AIM Program, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Ste A047N, Los Angeles, CA 90048; vankriekinges@cshs.org J Nucl Cardiol 2015;22:493–5. 1071-3581/$34.00 Copyright 2015 American Society of Nuclear Cardiology.

Gated radionuclide ventriculography (RNV), combined with inter- and intraventricular dyssynchrony measurement by phase analysis, is able to evidence right and left ventricular mechanical cardiac disorders and may contribute to the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). Nevertheless, the patients referred for suspicion of ARVD on the basis of symptoms, electrical abnormalities or family history of sudden death, are very heterogeneous and the examination findings spread out from strictly normal to severely abnormal. In order to describe the patient population encountered in "real life" we propose to use an automatic clustering method based on RNV results in order to segment the overall population into subgroups with coherent scintigraphic data in each one. A series of 130 consecutive patients presenting with various criteria suggestive of ARVD has been studied over a 3-year period. Seven variables have been extracted from gated RNV: left and right ejection fractions, visual semi-quantitative assessment of left and right ventricular volumes, left and right phase standard deviations and inter-ventricular dyssynchrony (IVD) measured from the phase histograms. The Self Organizing Map (SOM) clustering method has been applied to these data with various numbers of variables (right ventricular values only or values from both ventricles) and an increasing number of classes from two to nine. Including left ventricular variables and IVD in the analysis results in significant changes in classification compared to right ventricular data alone. Clustering into nine classes seems to be the most pertinent one and separates patients into four groups of normal result or insignificant left, right or bilateral abnormalities, two groups of isolated right ventricular abnormalities of increasing severity and three groups of severe bilateral abnormalities, right predominant with and without IVD, and left predominant. Automatic clustering of patients on the basis of scintigraphic results helps to understand the signification of the large spectrum of results encountered in clinical practice for patients whose common characteristic is to present some abnormalities or risk factors leading to investigations in the context of suspicion of ARVD. Although the final diagnosis remains questionable in a large proportion of patients, the knowledge of the various profiles of gated blood pool phase analysis may help for stratification of patients at risk of ARVD.

We evaluated the accuracy of planar radionuclide angiography and different count-based and space-based electrocardiogram (ECG)-gated blood-pool single-photon emission computed tomography (GBPS) algorithms for assessment of left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) compared with the gold standard of cardiac magnetic resonance imaging (cMRI). The goal is to assess the accuracy of a recently developed GBPS algorithm.Subjects had planar, GBPS, and cMRI sequentially. Datasets were processed by QBS software (Cedar-Sinai) and by MHI software (Montreal Heart Institute). Space-based approaches were used to compute LVEDV, LVESV, and LVEF. Count-based techniques were also used to assess LVEF. All results were compared to cMRI. Fifty-five patients (85% male; mean age 63 +/- 9 years) completed the study. LVEFs and their correlations to cMRI values were 43 +/- 12% (r = .82), 39 +/- 14% (r = .82), and 39 +/- 13% for MHI(space), QBS(space), and cMRI methodologies, respectively. LVEF by count-based methods also demonstrated good correlation to LVEF provided by cMRI (42 +/- 13%, r = .88 for MHI(count) and 46 +/- 15%, r = .84 for QBS(count)). Strong correlations were obtained for LVEDV (r = .96 for MHI and r = .92 for QBS) and for LVESV (.97 for MHI and r = .94 for QBS).All Gated blood-pool SPECT algorithms had significant variation in estimating LVEF. Nevertheless our software provides good estimates of LV volumes and LVEF. Such software may, therefore, be applied to assess LV morphology and function.

Beta-blockers are mainstay of current treatment of heart failure (HF). Beta-adrenergic receptors (AR) single nucleotide gene polymorphisms (SNPs) may influence the sensitivity and density of beta-AR. We assessed the relation between three common beta-AR SNPs and the response to carvedilol administration.We studied 183 consecutive patients with chronic HF due to ischemic or nonischemic cardiomyopathy, a LV ejection fraction (LVEF)or = 0.35, not previously treated with beta-blockers. Each patient underwent gated-SPECT radionuclide ventriculography, cardiopulmonary exercise testing and invasive hemodynamic monitoring at baseline and after 12 months of carvedilol administration at maintenance dosages. The beta1-AR gene Arg389Gly and the beta2-AR gene Arg16Gly SNPs were not related to the response to carvedilol administration. Homozygotes for the Glu27Glu allele showed a greater increase in the LVEF, compared to the other patients (+13.0 +/- 12.2% versus +7.1 +/- 8.1% in the Gln27Gln homozygotes, and 8.3 +/- 11.4% units in the Gln27Glu heterozygotes; p = 0.022 by ANOVA). Glu27Glu homozygotes also showed a greater decline in the pulmonary wedge pressure both at rest and at peak exercise. Gln27Glu SNP was selected amongst the determinants of the LVEF response to carvedilol at multivariable analysis, in addition to the cause of cardiomyopathy, baseline systolic blood pressure and the dose of carvedilol administered.Beta1-AR Arg389Gly and beta2-AR Arg16Gly SNPs are not related to the response to carvedilol therapy. In contrast, the Gln27Glu SNP is a determinant of the LVEF response to this agent in patients with chronic HF.

Recently, it has been reported that large infarcts associated with terminal QRS distortion (QRSDIS) on the admission electrocardiograms of patients with ST-elevation myocardial infarctions (STEMIs) may be caused by a failure to achieve thrombolysis in myocardial infarction (TIMI) grade 3 flow after primary percutaneous coronary intervention (PCI). However, the relationship between QRSDIS and final infarct size when TIMI grade 3 flow could be achieved by primary PCI is still unclear. Sixty-two consecutive patients with first anterior STEMI and who achieved TIMI grade 3 flow by primary PCI were classified into two groups according to the presence (Group A, n = 18) or absence (Group B, n = 44) of QRSDIS. Two weeks after the onset of acute myocardial infarction, Group A had a larger left ventricular (LV) end-systolic volume index (LVESVI) and a lower LV ejection fraction (LVEF) than Group B (LVESVI: 38 +/- 13 vs 31 +/- 12 ml/m(2), P = 0.025: LVEF: 42% +/- 10% vs 51% +/- 10%, P = 0.004). Through multivariate analysis, independent predictors of poor LV systolic function (LVEF < 40%) were determined to be the presence of QRSDIS (odds ratio 21.04, P = 0.021) and proximal left anterior descending artery occlusion (odds ratio 16.15, P = 0.033). Myocardial damage could not be reduced in patients experiencing STEMI with QRSDIS, even when TIMI grade 3 flow could be achieved by primary PCI, as much as in patients experiencing STEMI without QRSDIS.

Among the variables that characterize mechanical cardiac performance, left ventricular ejection fraction (LVEF) has attracted broad clinical interest, as various studies have provided ample evidence that LVEF is a major prognostic parameter [1–4]. Also, LVEF is among the selection criteria for device-based anti-arrhythmic or resynchronization therapy [5, 6]. Several imaging techniques allow for the assessment of LVEF, e.g., 2D and 3D echocardiography, gated SPECT, contrast angiography, cardiovascular magnetic resonance imaging (CMR) and computed tomography [7]). In patients with suspected ischemia, a common strategic sequence in which imaging techniques are being utilized is echocardiography, gated SPECT and coronary angiography, the latter frequently combined with or followed by intervention. As these three imaging techniques may all yield LVEF values it is not uncommon in clinical practice to have access to multiple LVEF measurements of the same patient. If, in one patient, these three LVEF values are available, what would be the measure of preference? The answer to this question depends upon the reliability of the measurement technique and on its proven prognostic value. Whether or not the echocardiogram, gated SPECT and the ventriculogram determined during angiography faithfully assess LVEF depends on a large variety of factors: the build of the patient, the technical quality of the equipment, amount of views (monoplane/biplane), quality of the analyzing software/algorithms, the potential for quantitative analysis, and of the operator/analyst being the most important ones [8–13]. Comparison with CMR, an important reference technique often being considered as a gold standard [14–19], can help in getting an impression of the relative accuracy of LVEF as measured by echocardiography, gated SPECT and contrast ventriculography [20–22].

Most training studies in patients with chronic heart failure (CHF) do not consider CHF aetiology in the interpretation of the results. About 60% of the patients in those studies have ischemic CHF (IHF) and 40% non-ischemic CHF (NHF). Recently, we conducted a randomized controlled trial to study three different training modalities in 60 patients with severe CHF, with a similar distribution of IHF and NHF patients. In the present post hoc analysis we compared the differences in training results between ischemic and non-ischemic patients.Left ventricular ejection fraction (EF), end diastolic volume (EDV), end systolic volume (ESV), measured with radionuclide ventriculography (RNV) and echocardiography, NT-pro BNP, peak oxygen uptake (peak V(O)(2)), working capacity and muscular volume were analyzed before and after training in 45 patients training for 40 sessions, 3 times per week. Fifteen patients served as control group. The outcome was analyzed considering the aetiology of CHF, either ischemic or non-ischemic.There were no significant differences in improvements of peak V(O)(2), working capacity and muscular volume between IHF and NHF patients. In NHF patients, EF increased while EDV and ESV decreased after training. These parameters remained unchanged in IHF patients after training. NT-pro BNP decreased significantly in NHF patients and increased in IHF patients after training. In the control group, patients showed a mild improvement of EF and a decrease of NT-pro BNP.This post hoc analysis shows that training intervention is associated with significant reverse remodelling in NHF, but not in IHF patients, whereas V(O)(2) peak and muscle volume improve regardless of CHF aetiology. Future prospective studies are needed to confirm our findings.

In 70 consecutive male patients with obstructive sleep apnea (OSA) diagnosed at the Northport VA Medical Center Sleep Disorders Center, we have characterized the association between obesity, OSA, and pulmonary hypertension (PH).By including anthropometric, pulmonary function, and sleep study parameters in a multivariate logistic regression model, we found that a BMI of40 kg/m(2) and the minimum oxygen saturation in non-rapid eye movement (NREM) sleep predicted the presence of pretibial edema in this sleep apnea population. We then characterized the hemodynamics of those OSA patients that had lower extremity edema. Twenty-nine of the 70 consecutive patients with sleep apnea (41%) had pretibial edema, and right heart catheterization data was obtained for 28 (97%) of these patients.Ninety-three percent (26/28) of the patients had right heart failure (mean RAP5 mm Hg; RAP range = 0-32 mmHg) and PH (PA meanor= 20 mm Hg) was present in 86% (24/28.) The OSA patients with lower extremity edema had an increased cardiac output (7.0 + 1.4 l/min) with a normal cardiac index (2.9 + 0.5 l/min/m(2)) in the setting of an elevated pulmonary capillary wedge pressure (PCWP 17 +/- 7 mmHg) and a normal pulmonary vascular resistance (122 + 70 dynes s cm(-5)). While PCWP, FEV(1)% predicted, and the minimum oxygen saturation in NREM sleep all independently predicted PH, PCWP was the most important predictor of PH.We conclude that pulmonary hypertension is commonly seen in patients with OSA with pretibial edema and that pretibial edema is a highly specific sign of PH in OSA patients. Pulmonary hypertension appears to result from an elevated back pressure and diastolic dysfunction with contributions from lung function and nocturnal oxygen saturation.

Evidence suggests that elevated plasma levels of B-type natriuretic peptide (BNP) are found in patients with chronic obstructive pulmonary disease (COPD) and right ventricular dysfunction. We examined the effects of exercise on plasma BNP levels in patients with COPD who have normal right ventricular functionSeventeen patients with a diagnosis of COPD and normal right ventricular function demonstrated by radionuclide ventriculography, and 17 age-and sex-matched healthy subjects underwent a treadmill exercise test. Plasma BNP levels were measured sequentially before, immediately after, and 1 hour after the exercise testThe mean plasma BNP+/-standard deviation levels of the COPD and control groups before exercise were 21.3+/-16 pg/ml and 13.4+/-11 pg/ml, respectively (P0.05). Mean plasma BNP level measured immediately after exercise was 37.9+/-31 pg/ml in the COPD group, reflecting a statistically significant increase when compared with the initial value (P0.05). The control group did not show any significant change in plasma BNP levels after the exercise testExercise induces an increase in plasma BNP levels in patients with COPD who do not have right ventricular dysfunction at rest. Measurement of exercise-induced BNP levels may be a useful alternative to pulmonary artery catheterisation in identifying the patients who are likely to benefit from long-term oxygen therapy.

Objectives To assess reproducibility of core laboratory performance and impact on sample size calculations. Background Little information exists about overall reproducibility of core laboratories in contradistinction to performance of individual technicians. Also, qualitative parameters are being adjudicated increasingly as either primary or secondary end-points. The comparative impact of using diverse indexes on sample sizes has not been previously reported. Methods We compared initial and repeat assessments of five quantitative parameters [e.g., minimum lumen diameter (MLD), ejection fraction (EF), etc.] and six qualitative parameters [e.g., TIMI myocardial perfusion grade (TMPG) or thrombus grade (TTG), etc.], as performed by differing technicians and separated by a year or more. Sample sizes were calculated from these results. TMPG and TTG were also adjudicated by a second core laboratory. Results MLD and EF were the most reproducible, yielding the smallest sample size calculations, whereas percent diameter stenosis and centerline wall motion require substantially larger trials. Of the qualitative parameters, all except TIMI flow grade gave reproducibility characteristics yielding sample sizes of many 100’s of patients. Reproducibility of TMPG and TTG was only moderately good both within and between core laboratories, underscoring an intrinsic difficulty in assessing these. Conclusions Core laboratories can be shown to provide reproducibility performance that is comparable to performance commonly ascribed to individual technicians. The differences in reproducibility yield huge differences in sample size when comparing quantitative and qualitative parameters. TMPG and TTG are intrinsically difficult to assess and conclusions based on these parameters should arise only from very large trials.

Use of radiation for medical examinations and test is the largest man-made source of radiation exposure. Interventional procedures are only 2% of all radiological procedures, but contribute to about 20% of the total collective dose per head per year. On average, a left ventriculography and coronary angiography corresponds to a radiation exposure for the patient of about 300, a coronary stent to 1,000, a peripheral artery intervention to 1,500 to 2,500, and a cardiac radiofrequency ablation to 900-1,500 chest x-rays. Invasive cardiology procedures increased tenfold in the last ten years and growth in the field has been accompanied by concern for the safety of the staff. Interventional cardiologists have an exposure per-head per year two- to three times higher than that of radiologists, with an annual exposure equivalent to around 250 chest x-rays per head. A reduction of occupational doses by a factor of ten can be achieved simply by and intensive training program. The awareness of radiation effects may be suboptimal in the medical community. It is recommended by professional guidelines and reinforced by the European law that the responsibility of all physicians is to minimize the radiation injury hazard to their patients, to their professional staff and to themselves.

The relation between serum level of amioterminal propeptide of type I procollagen and diastolic dysfunction in hypertensive patients without diabetes mellitus: a pilot study

Most patients with Primary Pulmonary Hypertension (PPH) have severe exertional limitation which ultimately leads to right heart failure and death. The purpose of the study was to assess the correlation between right ventricular (RV) systolic and diastolic noninvasive variables and exercise tolerance, as well as the predictors of adverse outcome in treated patients.We prospectively studied 29 patients, 17 with PPH and 12 with PPH due to collagen disease. RV parameters were assessed by echocardiography and Radionuclide ventriculography. Pulmonary function and clinical profile were assessed by 6 min walk test and NYHA class. The patients were followed-up during 2 years for cardiac death and cardiac deterioration.Mean age was 51 +/- 15 years, 22 (78%) women. NYHA class1 in 2 pts, class 2 in 17, class 3 in 8 and class 4 in 2 pts. Pulmonary function (DLCO) was low in 25 (86%) pts, mean 22 +/- 48%. Six minutes walk distance was 358 +/- 132 m, RVEF was 34 +/- 11% (range 16-51%). Among RV variables, RVEF, RA area and TR were independently correlated to 6 min walk. Within follow up of 2 years, there were 10 patients with adverse outcome (4 deaths and 6 deteriorated to NYHA class 3 and 4). Among all clinical and noninvasive variables, RVEF only was correlated to adverse outcome.The noninvasive tests of RVEF, RA size and TR were closely correlated to exercise tolerance. However, among the various clinical, functional and RV variables, RVEF was the only variable correlated with adverse outcome in pts with PPH.

This study prospectively assessed whether Tei index is predictive of early systolic dysfunction in adults undergoing adriamycin treatment.Left ventricular ejection fraction (LVEF) was obtained by radionuclide ventriculography at baseline and after treatment. Tei index was evaluated by echocardiography at baseline, at an intermediary cycle and at the end of chemotherapy. Fifty-five predominantly female patients (91%) with breast cancer (80%) and without known cardiac disease were evaluated. After treatment (adriamycin dose of 304 +/- 47 mg/m(2)), systolic dysfunction (final LVEF50%) occurred in eight patients (14%). Baseline, intermediate or variation of Tei index were not accurate to predict early systolic dysfunction ("c" statisticsor = 0.60). Baseline Tei index0.39, for example, had a sensitivity of 75%, specificity of 55%, positive predictive value of 22% and negative predictive value of 93%.Tei index does not appear to be a useful tool for detection of early adriamycin cardiotoxicity in adults.

Background A 71-year-old woman presented with severe chest pain after an episode of acute emotional distress. Her serum levels of cardiac enzymes were slightly elevated and electrocardiography revealed anterior ST-segment elevations. Significant coronary stenoses were excluded. A left ventriculogram revealed apical ballooning and a hypercontractile basal segment. Investigations Serum cardiac enzyme measurements, echocardiography, coronary angiography and left ventriculography. Diagnosis Takotsubo cardiomyopathy Management Treatment with β-blockers, aspirin, angiotensin-converting-enzyme inhibitors, and intravenous diuretics.

Aims: Test the accuracy of contrast enhanced harmonic color Doppler technique (CHCD) to determine left ventricular volumes and ejection fraction (LVEF) compared to equilibrium radionuclide ventriculography (MUGA). Methods and results: A total of 35 patients were enrolled (male 74.3%) with the mean age of 64.5 ± 10 years and 6.8 ± 4.9 days between echo and MUGA scans. The correlation of LVEF by CHCD with MUGA was better (R2 = 0.89) than that of harmonic 2D (H2D) and of contrast enhanced harmonic 2D (CH2D) (R2 = 0.74, R2 =0.82, respectively). The RMS residual of CHCD (0.056) was smaller than that of H2D and CH2D (0.079, 0.067, respectively). The LVED and LVES volumes by H2D, CH2D and CHCD correlate well with MUGA but there was a significant over estimation of LVED and LVES volumes by H2D and CH2D as compared to MUGA. Also, the RMS residuals were the lowest for the CHCD method. The CHCD had the highest mean inter-observer agreement (90.9%) for LVEF compared with H2D and CH2D (78.9% and 88.1%, respectively). Conclusions: CHCD has been feasible in all patients in the present study and it has shown a good concordance with ejection fraction and volumes provided by MUGA.

WOS: 000236782700016 PubMed: 16261279 Objective: The main aim of the study was, to estimate the impact of perfusion defects including significantly depleted areas of varying size on gated perfusion SPECT (GPS) determined ejection fraction (EF) measurements in comparison to radionuclide ventriculography (RVG). A secondary objective was the evaluation of the GPS-RVG agreement of EF in patients with normal and deteriorated left ventricular function, separately. Methods: Fifty-nine patients having perfusion defects including at least one segment with no visible tracer uptake in rest myocardial GPS related to myocardial infarction (older than 15 days) were studied. Myocardial perfusion was visually analyzed using a 17 segment-model, on a five-point (0-4) grading system in which Grade-4 (0-9% maximal uptake) represents cold defects. The patients with >= 4 adjacent, with 2-3 adjacent and with 1 single cold segments were named as Group1(GR1), Group2(GR2) and Group3(GR3), respectively. Secondly, the patients were re-grouped according to RVG-EF values. (Group A: patients with EF < 50%; Group B: patients with EF 0.05). The RVG-mean differences and RVG-correlation coefficients calculated for GR1,GR2 and GR3 were dEF%=3.1 +/- 4.6, r=0.85; dEF%=3.7 +/- 6.03, r=0.80 and dEF%=6.2 +/- 8.03, r=0.79, respectively. Mean dEF% was statistically higher in group-B than group-A (mean difference of dEF%=4,2, p < 0.05). In group-A, GPS-EF values were better agreed with RVG (dEF%=3.34, r=0.75) than in group-B (dEF%=7.52, r=0.53). Conclusion: The stability of the calculation algorithm of QGS in EF calculation of patients with large depleted infarct areas could be confirmed. The agreement of GPS determined EF is higher in patients having myocardial integrity loss and left ventricular dysfunction.

Aim: To analyse the clinical outcome and myocardial perfusion and function after transmyocardial revascularisation (TMR) in patients with normal left ventricular function and multivessel coronary artery disease non-amenable for standard revascularisation. Method and results: Twenty three severely symptomatic patients (CCS score median 4) with normal left ventricular systolic function but coronaries non-amenable for either PTCA or CABG were subjected to TMR. The angina score, left ventricular systolic and diastolic function in radionuclide ventriculography at rest, exercise tolerance and myocardial perfusion – Thallium-201 SPECT (adenosine stress 74 and 37 MBq under nitrate cover) were evaluated before and 3, 6, 12 months post-operatively. After an average of 40 ± 12 (range 14–56) TMR channels angina score decreased significantly (p< 0.0001) and the exercise tolerance increased (from 6.0 ± 4.5 to 9.1 ± 4.6 after 6 months, p< 0.05) in 21 patients. During the follow up period two patients had a myocardial infarction and one committed suicide after 6 months. Ejection fraction dropped significantly only after 1 year post-TMR from 70 ± 13 to 63 ± 0.13%, p < 0.05. The overall perfusion improved initially in 14 patients with subsequent deterioration in time. The changes in segmental perfusion were not associated with the symptomatic improvement. Conclusion: Transmyocardial revascularisation in patients with normal ejection fraction may improve the angina class, exercise tolerance and overall but not segmental perfusion and does not show any immediate effect on left ventricular function.

This study aimed to assess the feasibility of cardiac global function evaluation during a whole-chest multi-slice CT (MSCT) acquisition in patients referred for suspicion of pulmonary embolism (PE), and to compare the results with planar equilibrium radionuclide ventriculography (ERNA). Ten consecutive haemodynamically stable patients (six female, four male; mean age 69.7 years; heart rate 65-99 bpm) with suspicion of PE underwent an MSCT and ERNA within a 6 h period. CT acquisition was performed after contrast medium injection by using 16x1.5 mm collimation and retrospective ECG gating. Left ventricular (LVEF) and right ventricular (RVEF) ejection fractions were calculated using dedicated three-dimensional software. Relationships between measurements obtained with MSCT and ERNA were assessed using linear regression analysis and reliability of MSCT was assessed with intra-class correlation coefficient. Bland-Altman analysis was performed to calculate limits of agreement between MSCT and ERNA. MSCT was performed successfully in ten patients with a mean acquisition time of 16.5+/-2.8 s. Functional cardiac evaluation was possible on CT for all patients except for one due to poor opacification of right ventricle. Linear regression analysis showed a good correlation between MSCT and ERNA for the LVEF (R=0.91) and the RVEF (R=0.89) measurements. Intra-class correlation was superior for LVEF (0.92) than for the RVEF (0.68). Bland-Altman plots demonstrated that MSCT substantially overestimated the ERNA RVEF. Morphological CT data demonstrated PE in four of ten of patients and alternative diagnoses in five of ten patients. Our study reveals that MSCT with retrospective ECG gating may provide in one modality a morphological and a functional cardiopulmonary evaluation. Comparison with ERNA demonstrated a good correlation for both ventricular ejection fractions.

The purpose of our study was to extract the two-dimensional (2D) cardiothoracic ratio from digital chest radiographs using image analysis software on a Magic View 300 system. We also wanted to investigate its correlation with cardiac function, as defined by left ventricular ejection fraction from MUGA scanning, and with the traditional one-dimensional cardiothoracic ratio. One hundred patients undergoing radionuclide ventriculography and concurrent digital PA chest radiography using a commercial selenium detector system were studied. The 2D cardiothoracic ratio was extracted by defining a region of interest around the cardiac and thoracic areas and calculating a ratio of the two pixel counts obtained. The one-dimensional cardiothoracic ratio was calculated in the traditional manner. Regression analysis was used to study the association between these ratios and the ejection fraction. The 2D ratio could be achieved on all radiographs after image manipulation. The traditional linear cardiothoracic ratio showed an inverse correlation with left ventricular ejection fraction (r = −0.45). The 2D cardiothoracic ratio showed an improved correlation (r = −0.52). Assuming that a left ventricular ejection fraction of 55% or more indicates normal cardiac function, the normal 2D cardiothoracic ratio is 0.23 or less and a ratio of 1:4 is suggested. The ratio of cardiac and thoracic area correlates better with cardiac function as assessed by left ventricular ejection fraction than the traditional linear cardiothoracic ratio. Two-dimensional cardiothoracic ratio is easily extracted and improves the data yield from digital PA chest radiographs on PACS systems.

To explore the myocardial perfusion by thallium-201 scintigraphy for patients with evidence of myocardial damage after scorpion envenomation.Prospective study over 1-year period.Medical intensive care unit of a university hospital (Sfax, Tunisia).We have prospectively included six patients admitted for scorpion envenomation over a period of 1 year in the 22-bed intensive care unit (ICU) of our university hospital. The evidence of myocardial damage was confirmed by electrocardiography and echocardiography in all patients. Myocardial perfusion scintigraphy ((201)Tl scintigraphy) coupled with radionuclide ventriculography ((99m)Tc) was performed for all patients, occurring 32 h on average (range 12-72 h) after the sting.Radionuclide ventriculography was abnormal in all cases; the abnormalities observed were similar to those observed by echocardiography. Moreover (201)Tl scintigraphy showed evidence of myocardial hypoperfusion in all cases. The myocardial hypoperfusion grade and localisation were more marked in the abnormal localisation shown by echocardiography and electrocardiography, compared to the normal wall. Repeated studies, obtained only in two patients within 6 and 15 days, respectively, showed considerable, but not complete, improvement of wall motion and myocardial perfusion. Segments with improved perfusion showed greatly improved regional wall motion.This study confirms the evidence of myocardial hypoperfusion after severe scorpion envenomation.

Background Peak oxygen consumption at maximum exercise (peak VO2) predicts survival in chronic heart failure (CHF) patients. Right ventricular ejection fraction (RVEF) at rest has been reported to correlate with peak VO2. We evaluated the strength and consistency of the association between peak VO2 and RVEF measured by different radionuclide ventriculography (RNV) techniques in a prospective cohort study. Methods and Results In 58 consecutive CHF patients (mean age, 53 years; 39 patients with dilated cardiomyopathy; 48 men), upright symptom-limited bicycle ergometry was performed. During exercise, ventilatory and gas exchange data were recorded and peak VO2 was calculated. RVEF was calculated by use of first-pass (FP) RNV with single and dual region of interest (ROI) acquisition and planar multigated acquisition (MUGA). Irrespective of the method used, RVEF showed no relevant correlation with the corresponding peak VO2 value (r _ 0.11 for FP single ROI, r _ 0.06 for FP dual ROI, r _ 0.16 for MUGA). Peak VO2 or changes in peak VO2 after 6 and 12 months of follow-up were not determined by RVEF measurements. Conclusion In CHF patients no association was found between peak VO2 at maximum exercise and RVEF at rest with different RNV techniques. Changes in exercise capacity are not reliably reflected by changes in RVEF measurements at rest.

The ventricular phase angle, a parametric method applied to Fourier phase analysis (FPA) in radionuclide ventriculography, allows the quantitative analysis of ventricular contractile synchrony. However, FPA reproducibility using gated blood pool SPECT (GBPS) has not been fully evaluated. The present study evaluates whether by using GBPS, the reproducibility of FPA could be improved over that in planar radionuclide angiography (PRNA).Forty-three subjects underwent both GBPS and PRNA, of which 10 subjects were normal controls, 25 had dilated cardiomyopathy, and 8 had various heart diseases. Interventricular contractile synchrony was measured as the absolute difference in RV and LV mean ventricular phase angle as delta(phi) (RV - LV). Intraventricular contractile synchrony was measured as the standard deviation of the mean phase angle for the RV and LV blood pools (RVSD(phi), LVSD(phi)). Two nuclear physicians processed the same phase images of GBPS to evaluate the interobserver reproducibility of the phase angles using data from the 43 study participants. Phase images acquired from PRNA were processed in the same manner.Excellent reproducibility of delta(phi) (RV - LV) was obtained with both GBPS (Y = -3.10 + 0.89 x X; r = 0.901) and PRNA (Y = -4.51 + 0.81 x X; r = 0.834). In regard to RVSD(phi) reproducibility was not adequate with PRNA (Y = 18.56 + 0.35 x X; r = 0.424), while it was acceptable with GBPS (Y = 5.22 + 0.85 x X; r = 0.864). LVSD(phi) reproducibility was superior using both GBPS (Y = 4.15 + 0.97 x X; r = 0.965) and PRNA (Y = -0.55 + 0.98 x X; r = 0.910).Our results demonstrate FPA obtained using GBPS to be highly reproducible for evaluating delta(phi) (RV - LV), RVSD(phi) and LVSD(phi), in comparison with the PRNA method. We thus consider GBPS appropriate for evaluating ventricular contractile synchrony.

All previous validation studies of quantitative gated single-photon emission tomography (QGS) have examined relatively few patients, and the accuracy of QGS thus remains uncertain. We performed a meta-analysis of data from 301 participants in ten studies that compared QGS using technetium-99m-labelled tracers with contrast left ventriculography (LVG), and from 112 participants in six studies that compared QGS with magnetic resonance imaging (MRI). Linear regression and Bland-Altman analyses were used to evaluate pooled data from individuals across the studies. The correlation between QGS and LVG for end-diastolic volume (EDV) (r=0.81, SEE=27 ml), end-systolic volume (ESV) (r=0.83, SEE=18 ml) and ejection fraction (EF) (r=0.79, SEE=8.3%) was good, as was that between QGS and MRI for EDV (r=0.87, SEE=34 ml), ESV (r=0.89, SEE=27 ml) and EF (r=0.88, SEE=7.2%). However, Bland-Altman plots indicated that LVG minus QGS differences for EDV generated a systematic and random error of 32+/-58 ml (mean+/-2SD), and that MRI minus QGS generated an error of 13+/-73 ml. In the subgroup of patients in whom ECG gating was set at eight intervals, QGS significantly underestimated EF by 7.6%+/-17.4% (mean+/-2SD) compared with LVG and by 6.3%+/-14.6% compared with MRI; no such underestimation was observed in the subgroup in whom ECG gating was set at 16 intervals. We conclude that in patients with ECG gating set at eight intervals, QGS systematically underestimates LV volumes and EF compared with both LVG and MRI. Since QGS also shows considerable variations around the systematic deviations, there remains uncertainty over whether an individual value determined with QGS approximates the true LV volumes and EF.

An attenuated inotropic response to beta-adrenergic stimulation has been documented in patients with severely depressed left ventricular (LV) function. Scant data exist regarding the effect of beta-adrenergic stimulation on LV diastolic function in human beings. Our objective was to evaluate the effect of dobutamine infusion on LV systolic and diastolic function in patients with severe ventricular dysfunction.We studied 26 patients (60 +/- 9 years) in stable condition with healed myocardial infarction and LV ejection fraction (EF) less than 35% by radionuclide ventriculography. LVEF, volumes, peak ejection rate (PER), peak filling rate (PFR), and peak systolic pressure-to-end-systolic volume ratio were calculated at the infusion rate of 5 and 10 gamma x kg(-1) x min(-1). At 5 gamma x kg(-1) x min(-1), no changes were observed in heart rate (75 +/- 16 beats/min vs 75 +/- 15 beats/min at rest), LVEF (23% +/- 8% vs 22% +/- 7%), and PER (1.40 +/- 0.48 end-diastolic volume per second [EDV/s] vs 1.30 +/- 0.48 EDV/s); however, a significant increase in PFR was observed (1.11 +/- 0.36 EDV/s vs 0.86 +/- 0.30 EDV/s, P.01). At 10 gamma x kg(-1) x min(-1), an increase in LVEF (25% +/- 10%, P.01) and PER (1.60 +/- 0.57 EDV/s, P.01) was observed; PFR (1.25 +/- 0.36 EDV/s, P.05) also increased, whereas heart rate (78 +/- 18 beats/min) was unchanged. No significant changes in LV volumes or in indices of LV contraction synchronicity were observed during infusion. Finally, the peak systolic pressure-to-end-systolic volume ratio was unchanged at 5 gamma x kg(-1) x min(-1) and significantly increased at 10 gamma x kg(-1) x min(-1).In stable patients with ischemic heart disease and severe LV dysfunction, beta-adrenergic stimulation may still induce a positive lusitropic response, despite attenuated inotropic and chronotropic responses; moreover, the effects on diastolic function occur earlier than those on systolic function.

Radionuclide myocardial perfusion imaging (MPI) has been on the rise in Europe and the USA. Details on nuclear cardiology in the Czech Republic are not available as yet, as it is impossible to obtain comprehensive data from official registers owing to different methods of reporting and data evaluation. A questionnaire concerning nuclear cardiology activity and practice in 2001 was sent to all nuclear medicine departments in the Czech Republic. All 48 departments completed the questionnaire. In 2001, 50 planar and 54 tomographic (SPET) scintillation cameras were used. The average age of the SPET cameras was 5 years (13% of SPET cameras were8 years old). Out of the 48 centres, 39 (81%) provided a nuclear cardiology service; the total number of cardiological studies was 15,740 in 2001 (1.5 studies/1,000 population/year). The most frequently employed method was MPI (81.7%), the frequency of which had increased by 10% compared with 2000; 26 of the 39 (67%) departments reported that MPI activity was increasing. Nevertheless, the Czech Republic nuclear cardiology activity remained below the European average (2.2/1,000 population in 1994) and, particularly, below activity in the USA (15/1,000 in 1997). The activity was rather unevenly spread. Whereas two centres with1,000 studies/year accounted for 20% of the total MPI studies, 16 of 39 (41%) departments exhibited low activity (200 studies/year) and accounted for only 15% of the total MPI studies. The use of SPET increased from 91% in 2000 to 94% in 2001 (only three institutes performed planar examinations). The most widely used tracer was (99m)Tc-MIBI (60% of total MPI), followed by (201)Tl (21%) and (99m)Tc-tetrofosmin (19%). ECG-gated SPET was employed by 20/39 (51%) centres, of which 11 (28%) performed it as a standard examination; 39% of the total MPI studies included this technique. Thirteen percent (5/39) of the departments used attenuation correction, and 69% (27/39) of the departments used a prone projection. Equilibrium radionuclide ventriculography, with 2,317 examinations (14.7%), ranked second among all nuclear cardiology methods, followed by first-pass angiocardiography (406 studies, 2.6%) and (18)F-FDG (163 studies, 1%).

Carvedilol treatment reduces the mortality rate in patients with congestive heart failure. It is not known whether carvedilol treatment is effective in heart failure patients with substantial cardiac sympathetic nerve dysfunction. The goal of this study was to determine the effect of chronic carvedilol treatment in patients with cardiac sympathetic nerve dysfunction of varying severity. In 22 congestive heart failure patients with idiopathic cardiomyopathy, sympathetic nerve function was assessed before and after 7.2 ± 2.7 months of carvedilol treatment with the use of iodine 123 metaiodobenzylguanidine (MIBG) imaging, radionuclide ventriculography, and transmyocardial norepinephrine sampling. Patients with relatively advanced impairment of cardiac sympathetic nerve function, as manifested by a baseline I-123 MIBG ratio lower than 1.40, had a statistically significant improvement in I-123 heartmediastinum ratio with carvedilol treatment, from 1.26 ± 0.12 to 1.39 ± 0.20 (P = .004). Of 10 patients with a baseline I-123 MIBG ratio lower than 1.40, 9 had an increase in the heart-mediastinum ratio with carvedilol treatment. Left ventricular ejection fraction increased from 25.4% ± 7.8% to 37.3% ± 14.7% (P

Left ventricular diastolic filling is a fundamental constituent of cardiac performance. Diastolic function in both adults and children can be routinely assessed by radionuclide ventriculography (RNV). It has previously been shown that factors such as heart rate (HR) and age can significantly modify diastolic performance in adults, thus limiting the clinical applicability of RNV diastolic indices. The aim of this study was to investigate various factors that may affect diastolic function in childhood. Seventy-nine children, aged 40 days to 15 years, were enrolled in the study; their HR ranged from 45 to 160 beats per minute (bpm). All had intact cardiac function and were submitted to baseline RNV prior to chemotherapy initiation for malignancies. Using stepwise linear regression analysis, HR was identified as the major factor affecting RNV diastolic indices during growth. Applying univariate regression models, diastolic indices were corrected for a referrence HR of 100 bpm; this substantially reduced variability of RNV diastolic indices along age increments, allowing for the establishment of reference ranges. In conclusion, HR was shown to be the major determinant of RNV diastolic indices during growth. Adjustment for this variable alone can offer reference ranges for the assessment of left ventricular filling in childhood.

Thirty adult patients with non-Hodgkin's lymphoma were studied to evaluate prospectively the significance of early decline in left ventricular ejection fraction after low cumulative doxorubicin dose (200 mg m−2) in predicting the later impairment of left ventricular function. Cardiac function was monitored with radionuclide ventriculography at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m−2. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10% units to a final left ventricular ejection fraction ⩽50%. Twenty-eight patients received doxorubicin ⩾400 mg m−2 and were evaluable for cardiotoxicity. Clinical heart failure developed in two patients (7%) after a cumulative doxorubicin dose of 500 mg m−2. Left ventricular ejection fraction decreased more than 10% absolute ejection fraction units to a final left ventricular ejection fraction ⩽50% in 10 patients (36%). Left ventricular ejection fraction decreased from 56±1.5% to 53.6±1.5% (P=0.016) in patients with no cardiotoxicity, and from 60.8±2.4% to 41.8±2.0% (P

We have compared echocardiography (echo) and radionuclide ventriculography (RNV) with magnetic resonance imaging (MRI) for the measurement of left ventricular (LV) volume and ejection fraction. Seventy asymptomatic patients were studied up to 12 days after first Q wave anterior myocardial infarction and again after 6 months. Each patient had LV volume measured by all three techniques within 24 hours of each other on each occasion. LV end-systolic and end-diastolic volume index (LVESVI and LVEDVI) and LV ejection fraction (LVEF) were measured using the modified Simpson formula (echo), a counts-based method (RNV), and a multislice area summation method (MRI). Radionuclide volumes were measured both with and without correction for attenuation of isotope. Echocardiography overestimated LV volume compared with MRI. Mean (SD) differences (echo–MRI) were: LVEDVI + 10.6 ml/m2 (16.8), LVESVI + 13.7 ml/m2 (12.9), LVEF − 8.5% (11.2). RNV underestimated both volume and ejection fraction compared with MRI. Mean differences (RNV–MRI) were: LVEDVI −25.4 ml/m2 (23.8), LVESVI − 5.0 ml/m2 (18.6), LVEF − 13.8% (10.4). Variability in the difference between echo and MRI and between RNV and MRI was very similar for LVEF (coefficient of variation 23.9% echo, 22.2% RNV) but there was greater variability in the radionuclide than the echo measurements of absolute volume. Variability of the radionuclide measurements was reduced by not correcting for attenuation, and this finding may improve the radionuclide technique for serial measurements of percentage change in volume. Long-term inter-study reproducibility of MRI for LVEF (coefficient of reproducibility) was 10.9%, for echo it was 10.6%, and for RNV it was 14.6%. We conclude that measurements of LV volume depend on the method used and are not interchangeable. Echocardiography agrees more closely with MRI than RNV for the measurement of absolute volume, but the two techniques are similar for the measurement of LVEF.

Background We aim to investigate the effect of utilizing aortic valve timing in the measurement of cardiac magnetic resonance (CMR)-derived ejection fraction (EF). Although CMR-derived left ventricular (LV) EF is the gold-standard for volumetric evaluation of the heart, it always reports higher values when compared to other modalities such as echocardiography and radionuclide ventriculography. The higher EF has often been attributed to better endocardial definition by CMR. In the ACCF/ACR/ AHA/NASCI/SCMR 2010 Expert Consensus Document on CMR, a 1987 paper is cited with utilizes the “maximal and minimal left ventricular cross-sectional area at the mid-ventricle” to identify end-systole and end-diastole. The 2013 CMR Guideline suggests phases with the largest and smallest global LV blood volume be utilized to identify end-diastole and end-systole. The same guideline also suggests aortic valve timing be utilized when arrhythmia or mitral regurgitation is encountered. We investigated the effect of different schemes on measured LVEF. Methods Standard retrospectively EKG-gated bSSFP short axis and LVOT cine images in 46 clinical patients in normal sinus rhythm with a range of EF (5.8 75.8 %) were acquired and analyzed. Scan parameters were as follows: in-plane resolution: 1.25 2.08 mm, slice spacing: 8 mm with a gap of 2 mm, reconstructed temporal resolution: 18.2 58.8 ms. Aortic valve opening and closing as a percentage of cardiac cycle was identified on LVOT images. Volumetric evaluation of short axis images was performed via semi-automated segmentation for all phases and all left ventricular slices (ITK-SNAP, Philadelphia PA). The schemes (shown in Table 1) were used to quantify LVEF. Scheme G was considered “true EF” and usied aortic valve opening and closing. Scheme F is intended to mimic real-time methods, which acquire slice-by-slice data and do not incorporate aortic valve timing or other external measures such as EKG.

We have developed new software which can evaluate left ventricular (LV) diastolic functional parameters from a quantitative gated SPET (QGS) program. To examine its accuracy, we compared these findings with the LV diastolic functional indices obtained from gated radionuclide ventriculography (RNV). Twenty-four patients were selected for this study. Gated SPET with technetium-99m tetrofosmin was performed and the QGS program was used with a temporal resolution of 32 frames per R-R interval. The LV volume of each frame was calculated and four harmonics of Fourier series were retained for the analysis of the LV volume curve. From this fitted curve and its first derivative curve, we derived LV systolic functional indices, e.g. ejection fraction (EF), peak ejection rate (PER) and time to PER (TPER), as well as LV diastolic functional variables, e.g. 1/3 filling fraction (1/3 FF), peak filling rate (PFR) and time to PFR (TPFR). Within 5±2 days, gated RNV was performed and diastolic functional parameters were determined by the same method. No significant difference was observed between the variables calculated by gated SPET and by gated RNV. There was a good correlation between EF, PER, TPER, 1/3 FF, PFR and TPFR determined by these two methods (EF: r=0.95, P

Clinical usefulness of bone marrow transplantation (BMT) remains limited by myocardial damage during the post-transplantation period. Measurements of plasma atrial and brain natriuretic peptides (ANP, BNP) during the acute post-transplantation period could serve to monitor cardiac complications since these peptides are known to increase in heart failure depending on its severity. We prospectively analyzed ANP and BNP levels from 14 days before to 100 days after BMT in 46 consecutive patients undergoing allogeneic (n=42) and autologous (n=4) transplantation. Cardiac performance was assessed by echocardiography and radionuclide ventriculography. BNP and ANP levels of the patients on admission (baseline: day-14) were 16.3+/-13.3 pg/ml and 14.4+/-8.8 pg/ml, respectively. There were two different types of changes in the BNP and ANP levels. The 21 patients in group I showed dual peaks of elevation on day 1 (BNP=164.4+/-136.0 pg/ml, P0.01; ANP=44.5+/-35.4 pg/ml, NS) and day 14 (BNP=233.9+/-106.2 pg/ml, P0.01; ANP=142.7+/-154.6 pg/ml, P0.05), whereas the remaining 25 patients in group II had a single peak on day 1 (BNP=124.5+/-124.9 pg/ml, P0.05; ANP=45.2+/-42.4 pg/ml, NS). The left ventricular ejection fraction on day 63 was unchanged in both groups of patients from the baselines. The time to peak filling rate, a parameter of diastolic function in the radionuclide ventriculography, was significantly prolonged in group I patients (by 30+/-53%), whereas unaffected in group II patients. These results suggest that plasma BNP monitoring for 2 weeks after BMT may be useful for early detection of patients at high risk for cardiac dysfunction in the post-transplantation period.

Since the development of a Swan-Ganz Thermodilution Ejection Fraction Catheter, several studies have been published which compare this technique for obtaining right ventricular ejection fraction (RVEFTD) with alternative methods. However, the reliability of RVEFTD measurements under exercise conditions remains undetermined. Therefore, the aim of the present study was to evaluate RVEFTD with the Gated Blood Pool method (RVEFGBP) under exercise conditions. Twenty patients with different cardiac diseases (coronary artery disease, valvular incompetence, cardiomyopathy) underwent right heart catheterization, including RVEFTD and simultaneous RVEFGBP determination at rest and during supine bicycle exercise. Cardiac index at rest-/exercise was 2.9 +/- 0.8/5.7 +/- 2.2 l/min/m2, mean pulmonary artery pressure was 15 +/- 5/25 +/- 8 mmHg, RVEFTD was 38 +/- 6/41 +/- 11% and RVEFRNV was 39 +/- 6/43 +/- 8%. Linear regression analysis showed a significant correlation between RVEFTD and RVEFGBP at rest (r = 0.72, p < or = 0.0005) and during exercise (r = 0.72, p < or = 0.0005). It is concluded that the Thermodilution Ejection Fraction Catheter is a useful device for reliable, repetitive and safe RVEF measurements, not only at rest but also under exercise conditions. This is clinically important, because RVEF, as a sensitive parameter of primary or secondary right ventricular dysfunction, can be determined in the course of standard right heart catheterization.

Although the myocardial gated single photon emission computed tomography (SPECT) technique makes it possible to assess concurrent myocardial perfusion and function, quantitative methods for analyzing and displaying gated SPECT data in 2- and 3-dimensional presentations for regional and global cardiac assessment have not been established.We have developed an automated quantitative method for assessing perfusion and function by means of technetium-99m sestamibi gated SPECT with a computerized technique combining count-based and image-based methods. We have examined its validity in 91 patients by comparing its results with those of conventional techniques: contrast left ventriculography and radionuclide angiocardiography. In addition to color-scale displays of regional function, simultaneous 3-dimensional presentations of regional wall motion and perfusion have been produced. High reproducibility of gated SPECT analysis with this algorithm was demonstrated; interoperator errors (%CV) were 2.6% to 5.5%, and good intraobserver reproducibility was confirmed by means of high correlation coefficients (0.954 to 0.989). Left ventricular volumes assessed by means of contrast left ventriculography and by means of the gated SPECT technique showed significant correlations (left ventricular end-diastolic volume, y = 1.01x - 9.7, r = 0.845, P.001, standard errors of the estimate [SEE] = 14 mL; left ventricular end-systolic volume, y = 1.03x - 1.4, r = 0.902, P.001, SEE = 6 mL). Left ventricular ejection fraction determined by means of gated SPECT with the new algorithm closely correlated with that determined by means of radionuclide ventriculography (y = 1.05x - 0.6, r = 0.891, P.001, SEE = 3 %). These parameters quantified by means of the present method correlated closely with those derived from the QGS program (r = 0.926 to 0.987).In comparison with conventional techniques, myocardial gated SPECT with automated quantitative analysis provides accurate and reproducible data for global and regional function. Quantitative concurrent assessment of myocardial perfusion and function by using 2-and 3-dimensional representations appears to be superior to other modalities and to contribute to nuclear cardiology practice.

To evaluate the relationship between the mental stress-induced decrease in left ventricular ejection fraction (LVEF) and the severity of exercise-induced ischaemia, 20 patients with stable coronary artery disease (CAD) underwent radionuclide ventriculography during mental stress testing and stress myocardial perfusion single-photon emission tomography (SPET). We also examined whether changes in haemodynamic and neurohormonal parameters are related to changes in LVEF during mental stress. The LVEF decreased from 54.8% +/- 17.7% to 49.8% +/- 16.2% with mental stress (P0.0005). Ten of the 20 patients (50.0%) had aor = 5% decrease in LVEF The remaining ten patients had no or a5% decrease in LVEF There was a significant correlation between the change in LVEF during mental stress and the size of the reversible defect on stress myocardial perfusion SPET (r = -0.80, P0.0005), with close regional correspondence (75% identical). This correlation was less strong in the 12 patients with a total defect score at rest of10 (r = -0.69, P = 0.014) than in the eight patients with a total defect score at rest ofor = 10 (r = -0.94, P = 0.001). The changes in blood pressure and heart rate were not significantly correlated with the change in LVEF, but the percent change in adrenaline concentration correlated with the change in LVEE It is suggested that mental stress impairs systolic function by inducing transient myocardial ischaemia. The effect of neurohormonal responses during mental stress on LV systolic function may also be important in patients with CAD.

Gated single photon emission computed tomography (SPECT) with automated methods allows the quantitative assessment of left ventricular function and perfusion; however, its accuracy must be defined for patients with large earlier infarctions and severe rest perfusion defects, in whom the estimation of endocardial and epicardial borders might be more difficult, even with automated edge-detection techniques.We prospectively compared the automated measurements of left ventricular ejection fraction (LVEF) and volumes from rest-injected gated Technetium 99m (Tc99m) perfusion SPECT with equilibrium radionuclide angiocardiography (ERNA) in 62 patients and the assessment of regional function with echocardiography in 22 patients. Forty-six patients had an earlier myocardial infarction (mean defect size, 34% of left ventricle; SD, 12.7%; range, 8% to 56%); 27 patients had large defects (or = 20% of left ventricle; LVEF range, 8% to 75%). LVEF, as determined with Cedars-Sinai software (quantitative gated SPECT), correlated well with ERNA (r = 0.941; y = 1.003x + 1.15; P.0001; SE of the estimate = 6.3%; mean difference -1.3% for LVEF) in the entire study population and in the subgroups of patients with an earlier infarction, severe defects, and large infarctions (or = 20% of the left ventricle). A correlation existed between gated SPECT and ERNA volumes (r = 0.882, y = 1.040x - 14.7, P.0001 for end-diastolic volume; r = 0.954, y = 1.147x - 13.9, P.0001 for end-systolic volumes with the count-ratio technique), but with wider limits of agreement. The exact segmental score agreement between gated SPECT and echocardiography for regional function was 79.8% (281 of 352, kappa = 0.682).Automated gated SPECT provides an accurate assessment of ejection fraction and regional function, even in the presence of an earlier myocardial infarction with large perfusion defects and significant left ventricular dysfunction.

Recently, we proposed the hypothesis that a vicious cycle exists in human hibernating myocardium (HM) between the progression of myocyte degeneration and the development of fibrosis [1]. We now investigated the pathomechanism of this cycle in more detail and established a correlation between the severity of the morphological changes and the degree of postoperative functional recovery of HM. HM was diagnosed by dobutamine echocardiography, thallium-201 scintigraphy and radionuclide ventriculography. Functional recovery was present at 3 months after coronary bypass surgery but remained unchanged at 15 months. Forty patients were subdivided into 2 groups: A with complete and B with incomplete recovery. Biopsies taken during surgery and studied by electron microscopy, immunocytochemistry, rt-PCR, and morphometry revealed myocyte degeneration and inflammatory and fibrinogenic changes in a widened interstitial space. We report here for the first time an upregulation of TGF-β1 evident by a 5-fold increase of fibroblasts and macrophages exhibiting a TGF-β1 content 3-fold larger than in control, and a > 3-fold increase in TGF-β1 mRNA by rt-PCR. The number of angiotensin converting enzyme (ACE) containing structures was increased (n/mm2: control - 11.4, A - 17.6, B - 19.2, control vs. A and B, p 32%, capillary density 39.0 μm. In HM a self-perpetuating vicious cycle of tissue alterations leads to progressive replacement fibrosis and continuous intracellular degeneration which should be interrupted by early revascularization.

Objective: This clinical study was designed to evaluate the postoperative cardiac function in patients after aortic valve replacement for aortic valve disease with increased left ventricular mass.Methods: Aortic valve replacement was performed in 117 patients using the St. Jude Medical valve. Their valve lesion was aortic regurgitation in 71, and aortic stenosis in 46. The mean value of the left ventricular mass index was 272 g/m2. The 117 patients were subdivided into 4 groups according to their preoperative left ventricular mass index-Group I (n = 35) with aortic regurgitation and a large left ventricular mass index (≧ 273 g/m2), Group II (n = 36) with aortic regurgitation and a smalll left ventricular mass index Group HI (n = 19) with aortic stenosis and a large left ventricular mass index, and Group IV (n = 27) with aortic stenosis and a small left ventricular mass index. The cardiac function was evaluated by radionuclide ventriculography.Results: In a comparative study of postoperative parameters among the 4 groups, the postoperative systolic and diastolic parameters of Group I patients were more significantly impaired compared with these parameters of the other 3 groups. The postoperative values the left ventricular mass index were significantly higher in Group I than in the other 3 groups. The 10-year survival rate was significantly lower in Group I than in the other 3 groups (30± 22% in Group I).Conclusion: Aortic valve replacement is recommended for patients with eccentric hypertrophy in the adequate clinical phase of patients whose left ventricular mass index is less than 272 g/m2.

Patients with obstructive sleep apnea syndrome (OSAS) are subject to an increased cardiovascular morbidity including right ventricular dysfunction. It is supposed that effective treatment improves or prevents negatively affected cardiovascular variables. Continuous positive airway pressure (CPAP) is widely used in the treatment of OSAS. This study evaluated the effects of long-term CPAP application over two years on right ventricular ejection fraction in seven consecutive patients (59.3±8.4 years; median 56.0) with OSAS and pretherapeutically impaired right ventricular function. Five of the seven patients showed an increase of right ventricular function under CPAP therapy resulting in a significant improvement of RVEF in the study group (39.9±4.4% (median 42.0) vs. 54.3±15.5% (median 57.0); p

The application of thallium-201 myocardial perfusion scintigraphy to asymptomatic adults has refined the prevalence and prognostic significance of exerciseinduced silent myocardial ischemia. The relatively high occurrence of silent ischemia in both sedentary and athletic older men is noteworthy. A cost-effective intervention to treat these apparently healthy subjects could have major economic implications. The similarity of risk factors for silent ischemia and clinical CAD reinforces efforts at early risk-factor modification to prevent the progression from silent to symptomatic status. Many studies that used radionuclide ventriculography have documented a reduced left ventricular ejection fraction response to maximal cycle ergometry with age. In addition we have observed that the stroke volume increase with exercise in older adults is accomplished by a greater left ventricular dilatation (ie, the Frank-Starling mechanism) than in the young. The blunted exercise-induced increase in ejection fraction in healthy older subjects, especially women, must be considered when exercise radionuclide ventriculography is used as a diagnostic tool for CAD. The increase in peak diastolic filling rate during exercise is also attenuated with age. An attractive explanation for the age-associated reduction in the left ventricular systolic and diastolic responses to strenuous aerobic exercise is a diminution of β-adrenergic responsiveness with aging.

Cardiac gated blood pool single photon emission computed tomography (GBPS) better separates cardiac chambers compared with planar radionuclide ventriculography (PRNV). We have developed a completely automatic algorithm to measure quantitatively the left ventricular ejection fraction (LVEF) from gated technetium 99m-red blood cells (RBC) GBPS short-axis 3-dimensional image volumes.The algorithm determines an ellipsoidal coordinate system for the left ventricle and then computes a static estimate of the endocardial surface by use of counts and count gradients. A dynamic surface representing the endocardium is computed for each interval of the cardiac cycle by use of additional information from the temporal Fourier transform of the image data sets. The algorithm then calculates the left ventricular volume for each interval and computes LVEF from the end-diastolic and end-systolic volumes. The algorithm was developed in a pilot group (N = 45) and validated in a second group (N = 89) of patients who underwent PRNV and 8-interval GBPS. Technically inadequate studies (N = 38) were rejected before grouping and processing. Automatic identification and contouring of the left ventricle was successful in 121/172 patients (70%) globally and in 76/89 patients (85 %) in the validation group. Correlation between LVEFs measured from GBPS and PRNV was high (y = 2.00 + 1.01x, r = 0.89), with GBPS LVEF significantly higher than PRNV LVEF (average difference = 2.8%, P.004).Our automatic algorithm agrees with conventional radionuclide measurements of LVEF and provides the basis for 3-dimensional analysis of wall motion.

Nineteen patients with limited systemic sclerosis (SSc) and without any cardiac symptoms were evaluated non-invasively for silent cardiac involvement using electrocardiography; M-mode, two-dimensional and Doppler echocardiography, and resting and post exercise radionuclide ventriculography. Left anterior hemiblock and mild pericardial effusion were seen in two patients. The interventricular septal thickness and left ventricular posterior wall thickness were greater in patients compared with controls. Patients with limited SSc also exhibited low early diastolic filling velocities and a low early diastolic atrial filling ratio. However, these values did not correlate with the age of the patient or disease duration. Eight patients (42.1%) were found to have cardiac dysfunction, of which four had combined systolic and diastolic dysfunction. Isolated systolic and diastolic dysfunction was seen in three patients and one patient, respectively. The age and disease duration in patients with cardiac dysfunction did not differ from patients without cardiac dysfunction. Functional cardiac involvement occurs in a large proportion (42.1%) of patients with limited SSc, and can be easily picked up by non-invasive methods such as echocardiography and radionuclide ventriculography. The prognostic significance of these findings requires further long term studies.

To understand the effect of hyperventilation (HV) stress in patients with spastic angina, left ventricular (LV) contraction was analyzed by quantitative phase analysis. The study was performed on 36 patients with spastic angina pectoris, including vasospastic angina pectoris (VspAP: 16 patients) and variant angina pectoris (VAP: 20 patients). First-pass radionuclide ventriculography (first-pass RNV) was performed at rest and after HV stress, and standard deviation of the LV phase distribution (SD) was analyzed. The SD was lower in patients with VspAP than in VAP (12.8 ± 1.4 degrees vs. 14.6 ± 2.2 degrees, p < 0.005) at rest. After HV stress, the SD (HVSD) tended to increase in VspAP patients (62.5%), whereas the SD decreased in VAP patients (70%). Due to HV stress, the percentage change in SD (%SD) in VspAP patients was 8.9 ± 23.7% whereas that in VAP patients was −9.1 ± 17.3% (p < 0.01). Moreover, phase histograms were divided into HVSD increase and HVSD decrease groups. The HVSD increase group had a decrease of HVEF, but the HVSD decrease group tended to have more decreased HVEF than the HVSD increase group. These results indicate that spastic angina pectoris patients show various responses to HV stress. The HVSD increase group might have additional myocardial ischemia due to regional coronary spasm. In contrast, in the HVSD decrease group severe LV dysfunction or diffuse wall motion abnormality might have been generated, and this caused a reduction in the SD value. Phase analysis would therefore add new information regarding electrocardiographically silent myocardial ischemia due to coronary spasm, and HV stress might increase sensitivity for the detection of abnormalities in quantitative phase analysis, especially in VspAP patients.

We studied the effect of correction of anemia with erythropoietin on left ventricular systolic and diastolic function at rest and exercise in 17 chronic hemodialysis patients by means of maximum exercise testing and equilibrium gated radionuclide angiocardiography on three occassions: 1) initial–before erythropoietin administration, 2) intermediate–at the time when the target hemoglobin level reached 100 g/l, and 3) long-term–after 12 months of therapy. After correction of anemia, the patients showed a significant improvement in their response to exercise regarding maximal work load achieved, exercise duration and recovery time. Ejection fraction and peak ejection rate remained unchanged during therapy. At rest, peak filling rate was reduced from 2.62 ± 1.0 (baseline) to 2.28 ± 0.9 (intermediate) end-diastolic volume per second, p < 0.01, while no significant difference was observed during exercise. The time to peak filling rate was prolonged significantly during EPO therapy from 157 ± 30 to 177 ± 28 ms at rest, p < 0.05, and from 101 ± 24 to 130 ± 27 ms during exercise, p < 0.01. By the time of the late study, there were no significant differences between the late and intermediate study. In conclusion, amelioration of anemia with erythropoietin in hemodialysis patients produced improvement in exercise capacity, but diastolic function worsened with therapy and this effect was maintained during the long-term treatment, while systolic function at rest and exercise remained unchanged.

Measurement of left ventricular ejection fraction is a common procedure in cardiology. This is not without reason. Left ventricular ejection fraction has proven to be an important predictor of mortality in patients with heart failure and after myocardial infarction [1, 2]. It is also frequently used to monitor left ventricular remodelling after myocardial infarction and to select patients for ICD therapy and biventricular pacing [3, 4]. Next to this, measurement of left ventricular ejection fraction is used to detect cardiac toxicity in cancer treatment, especially chemotherapy with anthracyclines and related compounds (doxorubicin, daunorubicin, idarubicin, epirubicin, anthraquinone mitoxantrone) and trastuzumab [5, 6]. Therefore determination of left ventricular ejection fraction has to be correct and reproducible. Fortunately, several techniques are available to measure left ventricular ejection fraction: echocardiography, nuclear imaging, magnetic resonance imaging, CT of the heart and contrast angiography. Echocardiography is the most commonly used technique, particularly because it is a cheap and easy to perform technique, gives no irradiation gives no patient discomfort and can be used anywhere. In addition, the technique can be used in settings where MRI cannot be used and in patient with irregular heart rhythm, which makes radionuclide angiography inaccurate. Unfortunately the technique is highly operator dependent and patient dependent. Left ventricular function is frequently measured with 2D techniques with extrapolation to a 3D structure, assuming, that the four chamber view and two chamber view give a correct display of this 3D structure. In this setting, visual assessment may not always be accurate [7, 8]. Intra observer and inter observer variability improves if quantitative assessment with the Simpson’s rule is used. In some patients echocardiography is technically cumbersome (Patients with pulmonary disease, women with large breasts and patients with deformations of the thorax). Contrast enhancement can improve estimates of left ventricular ejection fraction significantly in this setting [9]. Magnetic resonance imaging gives also no radiation exposure, but is more difficult to perform and more expensive. Because of the high resolution of the images, the high endocardial intrinsic contrast, the absence of foreshortening, the absence of user-dependence, the high reproducibility, the ability to perform 3D images and the moderate to high temporal resolution, MRI has become the gold standard for the last two decades [10]. Nuclear imaging, CT of the heart and contrast angiography give radiation exposure, and are therefore contraindicated in pregnant women, are relative expensive and require contrast agents (CT and contrast angiography) with possible adverse effects. Radionuclide ventriculography was introduced three decades ago and soon became an accepted technique for measurement of left ventricular ejection fraction. This L. H. B. Baur (&) Department of Cardiology, Atrium Medical Centre Parkstad and University of Maastricht, Henri Dunantstreet 5, 6401CX Heerlen, The Netherlands e-mail: l.baur@atriummc.nl