Abstract P79  was publRight heart failure is a prevalent mechanism of cardiovascular collapse and distinctly different from left heart failure. Afterload reduction has been the main focus to treat right ventricular (RV) dysfunction, but it cannot be achieved in many cases. A new strategy is to directly target increased RV hypertrophy. Pulmonary artery banding (PAB) is used to induce the RV hypertrophy, without any changes in the pulmonary vasculature. The nitric oxide (NO) pathway was shown to be crucially involved in the development of left ventricular hypertrophy. In this study we assessed the effects of the sGC stimulator BAY 41-8543, the PDE5 inhibitor sildenafil, and combination treatment on RV function and RV hypertrophy.Chronic pressure-overload RV hypertrophy was induced by PAB in male C57/Bl6 wild-type mice. Drug treatment was started seven days after surgery for the duration of 2 weeks, after which the consequences of the sustained pressure overload on RV morphology and function were assessed using Magnetic Resonance Imaging (MRI) and RV catheterization. Furthermore, fibrosis was assessed by histology.Three weeks after PAB, placebo-treated mice showed several signs of RV dysfunction as compared to sham-operated mice. PAB led to RV systolic dysfunction, as indicated by an increase in end-systolic volume (17.3±1.0 ml vs. 29.2±2.5 ml [Sham vs. PAB]), decreased RV stroke volume (40.5±2.3 ml vs. 23.0±3.3 ml) and decreased RV ejection fraction (70.0±1.0 % vs. 43.0±3.5 %). Treatment with sildenafil did neither lead to significant changes in RV end-systolic volume, RV stroke volume nor RV ejection fraction, whilst treatment with BAY 41-8543 and combination treatment led to significant improvements. . PAB mice showed RV hypertrophy (0.022±0.003g vs. 0.032±0.006g) and an increased RV/(LV-S) ratio (0.25±0.03 vs. 0.39±0.1). Drug treatment had no effects on either RV hypertrophy nor RV/(LV+S) ratio. RV pressure was increased in PAB mice (30.0±3.0 mmHg vs. 50.8±12.2 mmHg) and did not change under drug treatment. Histological assessment of fibrosis showed that the collagen content increased in banded mice, sildenafil had no effects on collagen content, and BAY 41-8543 and combination treatment both decreased the amount of collagen .Even though none of the drug treatments led to significant changes in RV mass, BAY 41-8543 and combination treatment with sildenafil led to significant improvements in RV function, accompanied by decreased fibrosis.


Objective: We aimed to evaluate the role of gated myocardial perfusion SPECT (MPS) and to investigate whether only the invasive coronary angiography (CAG) is sufficient in the diagnosis of the coronary artery disease (CAD) in women. Material and Methods: Sixty-four women (62±10 years) with known CAD were included in this study. They had echocardiography (ECHO), stress/rest gated MPS and invasive CAG. Coronary stenosis as of > 50 % in invasive CAG was accepted as significant. Gated MPS data were compared with invasive CAG and ECHO. Results: Invasive CAG results were abnormal in 34 patients, and normal in 30 cases. Myocardial ischemia was detected by gated MPS in 22/ 30 cases with normal invasive CAG, 6 had mild coronary stenosis in major coronary arteries ranging from 30% to 50% in invasive CAG. 16/ 22 women were diagnosed as metabolic syndrome according to MetSend Diagnostic Criteria and only 8 of 30 patients with normal invasive CAG had false positive MPS data on the reevaluation by a nuclear cardiologist.Conclusion: We think that invasive coronary angiography method is not sufficient alone in the diagnosis of CAD in women. Gated MPS study is recommended to achieve the final decision for myocardial ischemia in the cases with CAD and raw data must always be evaluated to avoid attenuation artifacts. Conflict of interest:None declared. The incidence of coronary artery disease (CAD) in women increases in the postmenopausal period and becomes equal with men at 60 years of age. It is known that CAD symptoms in women are frequently confused with non-cardiac symptoms and most of the cases are misdiagnosed in emergency units. In western population, two thirds of women who die suddenly from coronary heart disease have no previous history of CAD ,2,3,4,5.Invasive coronary angiography (CAG) is a widely performed procedure in the diagnosis of CAD because treatment is also possible in the same session if a severe occlusion is detected ,9. HowevIn this study, we aimed to evaluate the role of gated MPS study in the diagnosis of CAD in female patients with myocard perfusion abnormality and second goal is to investigate if the invasive coronary angiography was sufficient alone particularly when the patients have metabolic syndrome. Sixty-four women who were admitted to our department in the last 3 years with typical angina pectoris, abnormal exercise ECG findings or the inability to perform the treadmill exercise test were enrolled in this retrospective study. All subjects had myocardial ischemia and/or infarction in any left ventricular myocardial segment and underwent invasive CAG within four weeks. Left ventricular systolic function  had also been assessed by 2D Doppler echocardiography (ECHO). All MPS images and gated studies were reevaluated by a nuclear cardiologist. Patients’ demographic data are summarized in Gated MPSAll subjects were instructed to discontinue their medications, such as long-acting nitrates, calcium channel blockers and beta blockers, at least 48 hours before the MPS study according to nuclear cardiology procedure ,20. At lGated MPS images were obtained with a CamStar AC/T gamma camera  equipped with LEGP collimator. The raw data was cinematically evaluated for attenuation and motion artifacts, after that, reconstructed stress and rest slices were simultaneously interpreted. Finally, left ventricular regional wall motion and myocardial systolic thickening were evaluated on stress gated images. If there is wall motion abnormality and/or decreased systolic thickening in the myocardial segment having reduced perfusion, this was accepted as true ischemia and if otherwise, not. Motion correction was not needed in any of the cases.Invasive CAG ProtocolCoronary angiography was performed through the femoral artery using the standard Judkins technique in the catheter laboratory of Pamukkale University Medical Faculty, Dept. of Cardiology. Vessel diameter, minimal lumen diameter and the percentage of luminal stenosis were measured using an automated analytic system. Cine-images were evaluated by an experienced cardiologist and lesions over 50% were considered serious coronary stenosis. Doppler ECHOStandard and pulsed Doppler tissue ECHO examinations were performed in all cases using a Vivid 7 ultrasound machine  with a 2.5-MHz phased array probe). Left ventricular wall motion and myocardial thickenning were visually evaluated by more than one cardiologist.According to invasive CAG results, stenosis of >50% in any vessel (single or multiple) was observed in 34 of 64 women with ischemic gated MPS. In this group, there were a single vessel coronary artery lesion in 18 (53%); 2-vessel disease in 11 (32%), and 3-vessel disease in 5 (15%) patients. Thirty patients were accepted as normal through coronary angiographic evaluation . Myocardial ischemia was detected on gated MPS images in 22 of 30 cases with normal invasive CAG report. Six of the 22 cases had mild coronary artery stenosis ranging from 30% to 50% in invasive CAG, and the MPS results were matched with invasive CAG findings. Unsignificant stenoses were observed in the LAD in 4 cases and in the RCA in 2 cases. These 6 cases had at least two of 4 risk factors  and also family history. In these cases, decreased myocardial perfusion was accepted as true ischemia because no soft tissue attenuation artifact was detected in unprocessed data, and ischemic segments were compatible with the localization of mild stenotic lesions on invasive CAG. 2, 2) Diabetes mellitus which is defined being on the usage of antidiabetic medication or having fasting glucose of ≥126 mg/dl, 3) hypertension, 4) hyperlipidemia (fasting triglycerides ≥150 mg/dl and HDL <50 mg/dl) and 5) hormonal changes (menopause)  were defined as endothelial dysfunction secondary to metabolic syndrome. Metabolic syndrome is determined according to the MetSend diagnostic criteria based on having at least three of the following ones: 1) BMI ≥30 kg/mnopause) ,22. Nonenopause) . LookingRegarding LV wall motion, gated MPS results were unmatched with ECHO findings in 9 of 34 cases having greater than 50% of coronary stenosis, and in 22 of 30 cases without any significant stenotic lesion on invasive CAG. All of the patients had normal ECHO findings in unstenotic group. In stenotic group, ECHO results were normal while gated MPS findings were abnormal in 9/34 cases. Matched gated MPS and ECHO findings were found for remained cases in both groups . Normal myocardial systolic thickening was detected in all cases which had normal wall motion on both gated MPS study and ECHO. Otherwise, cases with abnormal wall motion on ECHO and gated study showed decreased systolic thickening.Macrovascular and/or microvascular pathologies cause myocardial perfusion abnormalities which result in LV dysfunction related with the extension and severity of stenotic lesions. Impairment in the LV blood supply and functions can be evaluated by several methods. Treadmill exercise test is the most widely used as a screening test for CAD, but its sensitivity and specificity are low and LV functions can not be evaluated . Second In this present study, 25 cases of 56  showed abnormal wall motion on both stress gated MPS and rest ECHO studies. In addition, 9 cases of 34 in abnormal invasive CAG group with abnormal wall motion on gated MPS had normal wall motion on rest ECHO. We thought that this difference might have arised from the gated MPS results which were obtained under stress however the ECHO results were obtained in the rest (baseline) position. Baseline transthorasic ECHO can diagnose real normal cases but mild left ventricular dysfunction may not be truly determined. It was presented in a comparative study with MPS, that the accuracy of myocardial ECHO results were improved during adenosine stress . The corAmong our study population, 6 patients had ischemic findings on gated MPS accompanied with less than 50% stenosis on invasive CAG. Coronary lesion was detected in LAD in 4 patients and RCA in 2 cases. Similar to our results, Sanlı et al.  and AdamOther important disorder is metabolic syndrome in women. In our presented study, metabolic syndrome was diagnosed in 16 of the 30 cases based on the MetSend diagnostic criteria ,22. MostFinally, we suggest that female population should be carefully evaluated for diagnosing CAD. Coronary angiography without gated MPS is not efficient alone in the diagnosis of ischemic heart disease in women. Also, baseline ECHO may not detect transient LV dysfunction resulting from mild to severe ischemia under stress and operator dependency is the major limitation. The gated MPS study will be useful in this risky group to define a reduced myocardial perfusion, and raw data must be evaluated to avoid attenuation artifacts. In the presence of ischemic findings on gated MPS images without severe stenotic lesion on invasive CAG images, CAD is suggested for diagnosis. Study limitations: Our study population is not large in this retrospective study. Total 97 females with invasive coronary angiography who are admitted for myocardial perfusion study were evaluated. But, 33 cases were excluded from our study because MPS scan was performed without gated procedure. The gated MPS scan was performed for the remaining 64 patients. Second limitation is that we did not find sensitivity, spesificity, PPV and NPV values because study population is not sufficient for reliability.


Interventricular dyssynchrony evaluated with cardiac magnetic resonance is an independent predictor of systolic dysfunction and left ventricular remodeling while intraventricular dyssynchrony is an independent predictor of LV diastolic dysfunction in patients with isolated LBBB. Comprehensive evaluation of both these parameters of dyssynchrony would be useful in selecting patients for cardiac resynchronization therapy.Dyssynchrony in patients with left bundle branch block (LBBB) plays an important role in the development of left ventricular (LV) dilation, systolic dysfunction, progression of heart failure and mortality. Intraventricular dyssynchrony (IntraVD) and interventricular dyssynchrony (InterVD) may have different impacts on myocardial structure and function in patients with LBBB. Our objective was to characterize the independent effects of IntraVD and InterVD on myocardial structure and performance.Thirty-two patients with isolated LBBB  were assessed using cardiac magnetic resonance imaging. IntraVD was defined as the difference between the time of maximum systolic wall thickness of the septum and lateral wall of the left ventricle. InterVD was defined as the time difference between the onset of pulmonic and aortic flow. Peak filling rate (PFR) and time to peak filling rate (TPFR) were measured as surrogates of diastolic function.InterVD had a moderate inverse negative correlation with LV ejection fraction (r2=-0.5), and a moderate positive correlation with LV end-diastolic volume index (LVEDVI) (r2=0.4) and LV end-systolic volume index (LVESVI) (r2=0.5). The IntraVD had no significant correlation with LV remodeling and function parameters. Multivariate analysis also demonstrated that InterVD was an independent predictor of left ventricular systolic dysfunction (p<0.0001), increased LVEDVI (p<0.01), and increased LVESVI (P<0.001).In terms of diastolic dysfunction, IntraVD had a moderate positive correlation with THFR (r2= 0.5) and moderate negative correlation with PFR (r2=-0.5). InterVD was not significantly correlated with any diastolic dysfunction parameter. Multivariate analysis confirmed that IntraVD was an independent predictor of left ventricular diastolic dysfunction .InterVD evaluated with CMR is an independent predictor of systolic dysfunction and left ventricular remodeling. IntraVD evaluated with CMR is an independent predictor of LV diastolic dysfunction. A comprehensive evaluation of both these independent measures of dyssynchrony could be helpful in improving the patient selection algorithm for cardiac resynchronization therapy.None.


Objective: The use of an esophageal stethoscope is a basic heart sounds monitoring procedure performed in patients under general anesthesia. As the size of the first heart sound can express the left ventricle function, its correlation with cardiac output should be investigated. The aim of this study was to investigate the effects of cardiac output (CO) on the first heart sound (S1) amplitude.Methods: Six male beagles were chosen. The S1 was obtained with the newly developed esophageal stethoscope system. CO was measured using NICOM, a non-invasive CO measuring device. Ephedrine and beta blockers were administered to the subjects to compare changes in figures, and the change from using an inhalation anesthetic was also compared.Results: The S1 amplitude displayed positive correlation with the change rate of CO . The heart rate measured using the esophageal stethoscope and ECG showed considerably close figures through the Bland-Altman plot and showed a high positive correlation .Conclusion: In beagles, the amplitude of S1 had a significant correlation with changes in CO in a variety of situations. Listening to heart sounds is also used in monitoring for arrhythmia and diagnosing heart disease.2-4 However, traditional chest auscultation can be impossible depending on surgery, and extraneous noise can occur due to body movement. Its usefulness also depends heavily on body weight and air movement in the thoracic cage. On the other hand, the esophageal stethoscope is advantageous in continuous evaluation of heart sounds because it can be placed in close proximity to the heart and undergoes minimal changes once it is fixed. The esophageal stethoscope can measure central temperature and has even been studied in the measurement of the residual flow of patients with patent ductus arteriosus.5 However, the use of the esophageal stethoscope has decreased with the development of transesophageal ultrasound. One of the reasons for the decline in use is that the obtained heart sound is not expressed objectively but instead relies on the judgment of the doctor and, thus, could be interpreted differently according to the expertise of the individual.Listening to heart sounds through a stethoscope is one of the basic examinations6, Korea). This system digitizes the analogue heart sound input for display and uses a program to perform noise removal and amplification. Our Laboratory has studied heart sounds.6 Based on previous study  10.1007/s10877-013-9459-0), this study was conducted.This study visualized heart sounds using the esophageal stethoscope and analyzed them quantitatively to investigate whether they can be used to evaluate heart function during surgery. To accomplish this, a new program and mechanical equipment were needed in addition to the existing esophageal stethoscope. Newly developed technology was used for the mechanical equipment and program . The hypothesis of this research was that a correlation exists between S1 amplitude with stroke volume (SV) and cardiac output (CO).Heart sounds comprise two main components: the first heart sound (S1), and the second heart sound (S2).8,9 the thoracic bioimpedance method,10 and the bioreactance method.11,12 Instead of the traditional thermal dilution method, this research used the bioreactance equipment NICOM , which is used in current clinical practice for monitoring heart sounds and analyzing correlations with S1, as it is non-invasive and has superior accuracy. In addition, to investigate whether the esophageal stethoscope can function as an independent monitor, the heart rate was obtained through S1 and compared with ECG.There are numerous methods to measure cardiac output continuously and in real time. However, in current clinical practice, non-invasive tools are being developed for use. Typical methods include the esophageal Doppler method,The hypothesis of this research was that the change in S1 amplitude obtained through the esophageal stethoscope has a correlation with cardiac output. An animal experiment was conducted to prove this hypothesis.6 This quantifies and expresses the amplitude of the heart sound and shows the cardiac cycle and heart rate . Six male beagles from 10 to 12 kg (11.1 ± 0.63) were chosen. Atropine sulfate 0.02 mg/kg was administered for premedication, and anesthesia was induced by subcutaneous injection of 2% xylazine hydrochloride 1 mg/kg. Isoflurane was used to induce inhalation anesthesia, and endotracheal intubation was performed through the oral cavity. Intermittent positive pressure ventilation was performed for respiration. The subjects were stabilized in a left lying position, and the esophageal stethoscope  was fixed at the position where the S1 sound was heard the loudest. The microphone, part of the digital heart sound measuring equipment, was connected to the esophageal stethoscope. The arterial pressure was measured via femoral artery. After the vital signs were stabilized, the S1 amplitude and standard for cardiac output were measured. The digital esophageal stethoscope system hardware comprises a microphone, microcontroller, amplifier, digital converter, and power connecting equipment. The heart sound analysis program recorded the data transmitted through the USB, while simultaneously visualizing the data. The MATLAB program  was used for the Heart Sound Analyser 1.0 developed by Park SH et al.art rate . The heaart rate . Situations similar to actual clinical scenarios were designed to investigate the correlation between S1 amplitude and cardiac output when inotropic agents and beta blockers were used. In these conditions, it was hypothesized that cardiac output and arterial pressure would show an accompanying increase and decrease. Ephedrine (0.2 mg/kg) was used as the inotropic agent and esmolol (1 mg/kg) as the beta blocker. Second, the change in S1 amplitude was examined when maintaining cardiac output while decreasing arterial pressure using isoflurane. The standard value was measured, and the Minimum Alveolar Concentration (MAC) of isoflurane was changed from 1MAC to 2MAC. Each variable—cardiac output, heart sound, and arterial pressure—was checked at 30-second intervals after measuring the standard value, and they were measured in end-expiratory pressure to reduce the interference of respiration sound. To compare values, heart rate was measured simultaneously with the esophageal stethoscope and ECG 100 times each using the pressor agent and beta blocker. SPSS  was used for statistical analysis. The changes in cardiac output, arterial pressure, and S1 amplitude were analyzed with the Pearson’s correlation coefficient method. The changes in S1 amplitude, cardiac output, heart rate, and arterial pressure with increasing concentrations of the inhalation anesthetic were compared with the standard value using one-way analysis of variance. A Bland-Altman plot was made using the MedCalc  program to compare heart rate in the esophageal stethoscope and ECG, and the correlation between the two measurements was analyzed using the Pearson’s correlation coefficient method. Statistical significance was defined as having a p-value of less than 0.05.The change rate in cardiac output and S1 amplitude changed according to the administration of the inotropic agent and beta blocker. The change in cardiac output per unit time (dCO/dt) showed a direct response after administering the pressor agent and beta blocker, and the graph showed differences with the change rate of S1 amplitude . The chaWhen the concentration of isoflurane was increased to 2MAC, the mean arterial pressure decreased (25.6% ± 4.12%), while heart rate significantly increased (27.3% ± 7.4%) . HoweverThe heart rate from the esophageal stethoscope and ECG was expressed through a Bland-Altman plot . Within 13 In these studies, however, heart sound amplitude was calculated using only the amplitude height; this is not considered to be very accurate, as the sound characteristics were not reflected fully. Our research calculated the RMS of the sound waveform to apply the size of the changing value. It is important to note that heart sounds have waveforms. This research calculated the root mean square (RMS) of the sound waveform to apply the size of the changing value. There has been precedent study reporting a positive correlation between S1 amplitude with SV and CO (r = 0.76).14 This experiment analyzed S1, but much research is being conducted on S2.15,16The first heart sound is made by the closing of atrioventricular valves and is heard loudly in the apex; the second heart sound is made by the closing of the aortic valve and pulmonary valve and is heard loudly in the base of the heart.17 estimating pulmonary arterial pressure,18 detecting heart disease,4 and evaluating left ventricle function.19 S1 is related to the maximum speed of increase in left ventricle systolic pressure (maximum dP/dt). This is because the isovolumic contraction period of the left ventricle is when the first heart sound is made, and as the pressure increases, the sound becomes larger accordingly.To the present, there has been multidimensional research on heart sound, which has been analyzed as a major factor in many studies regarding its relationship with respiration,20In this experiment, the first heart sound showed a high correlation with changes in cardiac output. The contractile power of the left ventricle would have increased when inotropic agents were used, and this would make the closing of the valves stronger. The opposite situation would have arisen when using beta blockers. In addition, the S1 amplitude was maintained when cardiac output was maintained using isoflurane. Isoflurane is the only inhalation anesthetic that maintains rather than decreases cardiac output when the concentration is increased.The fact that the first heart sound has a correlation with cardiac output is very meaningful in various situations, and it is more significant given the fact that the heart rate can be deduced independently. It is highly probable that surrounding noise that was not completely removed accounted for the slight difference in heart rate between the esophageal stethoscope and ECG. Although not separated and processed statistically, almost exact concordance was shown in a quiet situation of end-expiratory period during the experiment.Continuous monitoring of cardiac output is very important during surgery or when treating critical patients. The importance increases when changes become extreme due to unstable hemodynamics. Monitoring will be meaningful if the S1 amplitude, which is proportionate to left ventricle contractile force, shows a correlation with cardiac output. Recently, there has been active development of non-invasive tools to measure cardiac output in clinical practice. These are being used in many studies as indicators of hydration as well as for the evaluation of heart function.21 In that study, when the NICOM device set the age of beagles weighing 12 kg or less at 7 years, it showed accurate concordance with cardiac output measured through the aorta in an invasive method. Of course, the relationship between adult heart function and heart sound obtained through precordial auscultation has been researched before, but almost no research has been conducted regarding the esophageal stethoscope. In addition, this experiment was conducted on normal dogs with no problems in their heart or valves in a heart ultrasound performed before the experiment. There are reports that heart sound differs before and after heart surgery.22,23 The largest factor involved in heart sounds is the closing of valves. If the mitral valve cannot close properly due to disease or calcification, the first heart sound can be small or difficult to detect. If research is conducted on hearts with disease, further relationships may be revealed.There are limitations to applying this experiment directly to clinical situations. An important point is whether the correlation found in animals can be similarly applied to adult humans. In this experiment, subjects were limited to dogs ranging in weight from 10 to 12 kg, which was the experimental model in Heerdt et al.The heart sound amplitudes in the subjects were expressed through ratios to the standard value. Generally, the amplitude of sound is expressed by decibel (dB), and the smallest sound that can be heard by normal adult ears is 0 dB. If the normal amplitude of heart sounds is expressed as it is, it will be minus dB. Therefore, this experiment calculated the change rate with heart sounds in a stable state as the standard value.In conclusion, the esophageal stethoscope is a non-invasive tool that can be placed in close proximity to the heart for monitoring. Through this experiment, it was revealed that the amplitude of the first heart sound has a correlation with cardiac output. In addition, the heart rate was accurately measured through the first heart sound. These results are considered to be meaningful for the goal to accurately monitor cardiac output safely and economically.Young Duck Shin & Kyoung Hoon Yim: Conceived, Designed and did statistical analysis & editing of manuscriptSang Hi Park, Yong Wook Jeon, Jin Ho Bae, Tae Soo Lee, Myoung Hwan Kim & Young Jin Choi: Did data collection and manuscript writing.Young Duck Shin: Did review and final approval of manuscript.


We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI).Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured.Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction , regional wall motion score index , and global longitudinal strain . The diastolic functional indices significantly correlated with age , LV twist , average non-infarcted myocardial circumferential strain , and LV end-diastolic wall stress index  but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury.In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function. The hemodynamics on infarcted or non-infarcted myocardium is related to left ventricular (LV) remodeling after acute myocardial infarction (AMI). Post-myPatients with AMI who underwent successful percutaneous coronary intervention (PCI) within 48 hours of chest pain were prospectively enrolled. AMI was diagnosed on the basis of elevated levels of cardiac enzyme and ST-segment or T wave deviation on electrocardiography (ECG) according to the established diagnostic criteria. ExclusiCardiac MRI was performed with a 1.5-T scanner  with a phased array body coil. The LV 2-chamber, 4-chamber, and short axis views were obtained using cine images with steady-state free precession sequence. The acquisition parameters were: repetition time (TR) = 55 msec, echo time (TE) = 1.1 msec, flip angle = 67°, 25 phases, slice thickness = 8 mm, slice gap = 2 mm, acquisition matrix = 192 × 109, and field of view = 320 × 400 mm. T2WI was performed in cardiac short-axis direction using a dark-blood T2-weighted short-tau inversion-recovery fast-spin echo sequence. Imaging parameters were TR of two heart beats; inversion time = 170 msec; TE = 47 msec; flip angle = 180°; turbo factor = 33; matrix = 119 × 256; field of view = 340 × 400 mm; slice thickness = 8 mm. LGE imaging with a magnitude- and phase-sensitive inversion recovery prepared fast gradient echo sequence was obtained in 10 minutes after administration of 0.2 mmol/kg of a gadolinium-based contrast agent . LGE imaging was obtained in the same axis and slice thickness used in the cine imaging. A bolus of contrast media was intravenously administered at 2 mL/sec, followed by 20 mL of normal saline at 4 mL/sec through a 20-gauge cannula in the antecubital vein using a power injector . The appropriate inversion time before LGE-imaing was determined using a fast gradient echo sequence with inversion times varying from 150-650 msec to null the signal from the normal myocardium. The LGE imaging parameters were: TR = 600 msec, TE = 3.4 msec, flip angle = 25°, acquisition matrix = 256 × 156; and field of view = 320 × 400 mm.2/3 – 1} from LaPlace’s lawce’s law, where ece’s law. Where EFrom the LGE images, LV was divided into 17 segments as recommended by American Heart Association. In eachEach patient underwent a complete standard transthoracic echocardiography. The LV volume and LV ejection fraction were measured by the biplane Simpson’s method as recommended by the American Society of Echocardiography. The lefFor the LV speckle tracking analysis, three parasternal short axis images , apical four- and two-chamber view images were obtained using conventional gray scale echocardiography . A minimum frame rate of 40 fps was required for the reliable operation of this program. Recordings were processed using acoustic-tracking software  that allowed offline, semi-automated analysis of speckle-based strain. From thTotal LGE score, percent LGE and number of high signal intensity in T2WI-CMR were used as an index of extent of LV myocardial infarction and extent of myocardial edema, respectively. As representative LV chamber systolic functional indices, LV ejection fraction, RWMSI, GLS, and GCS were used and as representative diastolic functional indices, E/e’, e’, LVEDWS, early diastolic-GLSr and early diastolic-GCSr by speckle tracking echocardiography were used.Clinical characteristics, echocardiographic, and CMR parameters are presented as mean ± standard deviation for continuous variables and number (percentage) for categorical variables. Correlation analysis was done between continuous variables with Pearson correlation coefficient. Intraclass correlation coefficients from average measures are calculated for repeated measured strain, strain rate and twist values. For the analysis of predictive value of diastolic function included age, gender, presence of diabetes, hypertension, percent LGE, LV ejection fraction, LV mass index, M/V ratio, LVEDWS, Twist, and non-infarcted myocardial CS. Among them dichomatous variables were used in gender, presence of diabetes and hypertension. Variables with a p < 0.05 in the univariable analysis were included in the stepwise forward method in the multivariable regression analysis. All the analyses were done using SPSS , and P values less than 0.05 were considered as significant.2 and LV ejection fraction was 53.0 ± 10.8% as assessed by CMR. The number of patients with an LV ejection fraction of less than <50% was 14 (37%), and 3 (8%) patients had an LV ejection fraction of less than 35%. Mean value of peak CK-MB was 122.8 ± 88.8 ug/L. The number of LGE-involved segments was 4.5 ± 2.4 and the average LGE amount was 21.1 ± 13.9 g . Seventeen patients (45%) had MVO. Percent LGE) was higher in the STEMI group (15.4 ± 9.7% vs. 12.9 ± 5.6% p = 0.500), while the time to reperfusion was longer in the non-STEMI group ; nevertheless, this was not significant.The mean age was 52.8 ± 11.8 years, and 35 (92%) were men. Thirty patients presented with ST-elevation myocardial infarction (STEMI), and eight were non-STEMI. The average time from onset of chest pain to PCI was 207.4 minutes, and the mean duration of performing CMR after PCI was 2.4 days. Twenty patients had left anterior descending artery territory lesions, three had left circumflex coronary artery territory lesions, and 15 had right coronary artery territory lesions. The mean Killip classification on admission was 1.7 ± 0.9 and the mean NYHA functional class at CMR was 1.4 ± 0.6.Baseline clinical characteristics are described in Table 1/s and 0.86 ± 0.34 1/s, respectively. The average value of twist was 17.9 ± 8.5°. The mean LV end-diastolic wall stress was 3.8 ± 1.4 kPa. The details of tissue Doppler indices and 2D speckle tracking echo results are described in Table The average e’ velocity was 6.7 ± 2.7 cm/s, E/A ratio was 1.03 ± 0.35 and E/e’ was 11.4 ± 4.7. GLS was -13.2 ± 3.9%. Systolic and early diastolic GLSr was -0.73 ± 0.23 Total LGE score was significantly correlated with peak CK-MB and peak troponin T, biomarkers of myocardial injury  and extent of Q wave. Total LGE score was significantly correlated with LV systolic function as measured by ejection fraction  and RWMSI . Their relationships remained significant wih%LGE . The correlation was also significant with the number of edema-involved segments . The number of edema-involved segments was significantly correlated with GLS , the average of three GCSs , and the systolic twist rate . These relationships were also significant with total LGE score. However the extent of edema did not correlate with peak twist  and only weakly correlated with early diastolic twist rate . Both the extent of LGE and %LGE were not significantly correlated with diastolic functional parameters. , E/e’ , early diastolic GLSr , and average early diastolic GCSr . In addition, age was significantly correlated with LV twist  and twist significantly correlated with diastolic functional indices such as E/e’, e’, early diastolic GLSr, and average early diastolic GCSr. , 0.880 (p = 0.003), and 0.570 (p = 0.081), respectively. Systolic GCSr and GLSr were 0.728 (p = 0.025) and 0.858 (p = 0.005), respectively. Early diastolic GCSr and GLSr were 0.593 (p = 0.051) and 0.916 (p = 0.001), respectively.In this study we found that the extent of myocardial scarring and edema were both significantly related to LV systolic function as measured by LV ejection fraction, RWMSI, GLS, and average GCS. In contrast to systolic function, the extent of myocardial injury was weakly or not significantly correlated with LV myocardial and chamber diastolic functional indices. Age, LV mass index, LVEDWS, LV twist, and non-infarcted myocardial circumferential strain were significantly correlated with LV diastolic functional indices. This suggests a significant contribution of age and non-infarcted myocardial characteristics to chamber diastolic function in patients with early reperfused AMI.Our data indicate that the extent of myocardial injury is significantly correlated to all three directional systolic deformational indices  and LV chamber systolic function. This firmly supports previous data that demonstrated a close relationship between the extent of myocardial injury and myocardial systolic function. HoweverContrary to the well-established close relationship between the extent of myocardial infarct and systolic function, the relationship between the extent of myocardial injury and chamber diastolic function is controversial,18. ExtrSeveral previous studies have shown that LV twist increases with aging, hypertension, and diabetes in order to compensate for impaired longitudinal function-24. Our First, we did not directly measure the tissue characteristics of the non-infarcted myocardium. Instead, we measured myocardial deformation and used this as an index of non-infarcted myocardial regional systolic or diastolic function. Novel imaging method such as T1 mapping may provide additional information on this healthy looking myocardial tissue. Secondly, when measuring circumferential strain of the non-infarcted myocardium, non-LGE or non-edema area could not be exactly matched with echocardiographic segments. We used average values for non-infarcted slices or segments, and the effects of this mismatch are likely small or negligible. Thirdly, when measuring LVEDWS we used tissue Doppler-derived LV end-diastolic pressure instead of an invasive method. This is an unavoidable limitation from using this approach. Fourthly, all the enrolled patients underwent timely, successful PCI resulting in a limited extent of myocardial injury. Therefore, the applicability of this study to all the myocardial infarction patients needs further evaluation. Lastly, using septal e' in patients with regional wall motion abnormalities may limitations but previous studies showed even in regional wall motion abnormality, E/e’ correlated to LV filling pressure, therefore this limitation would not change the results.The authors declare that they have no competing interests.HC and EYC made the study design and wrote the manuscript. CHP, EYC and THK analyzed CMR images, EJK analyzed the speckle tracking echocardiography. HC and JHY collected the echocardiographic and clinical data. YWY, JYK, BKL, PKM, BKH, SJR and,HMK collected the clinical data and angiographic data. All authors read and approved the final manuscript.


Some patients with chronic ischemic left ventricular dysfunction have shown significant improvements of contractility with favorable long-term prognosis after revascularization. Several imaging techniques are available for the assessment of viable myocardium, based on the detection of preserved perfusion, preserved glucose metabolism, intact cell membrane and mitochondria, and presence of contractile reserve. Nuclear cardiology techniques, dobutamine echocardiography and positron emission tomography are used to assess myocardial viability. In recent years, new advances have improved methods of detecting myocardial viability. This paper summarizes the pathophysiology, methods, and impact of detection of myocardial viability, concentrating on recent advances in such methods. We reviewed the literature using search engines MIDLINE, SCOUPS, and EMBASE from 1988 to February 2012. We used key words: myocardial viability, hibernation, stunning, and ischemic cardiomyopathy. Recent studies showed that the presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and LV dysfunction, but the assessment of myocardial viability did not identify patients with survival benefit from revascularization, as compared with medical therapy alone. This topic is still debatable and needs more evidence. Coronary artery disease (CAD) remains a principal cause of morbidity and mortality worldwide . Many suThe first view of adaptation involves dedifferentiation or embryonic regression, the so called “smart heart” hypothesis . The proStunning is another form of reversible segmental myocardial dysfunction in the setting of normal myocardial perfusion. Heyndrickx et al.  observedClassically, hibernation was thought to occur with sustained hypoperfusion, especially during tachycardia but with adequate residual flow to allow survival of the tissue in the lack of contractile activity . In contIt was originally assumed that the recovery of function when hibernating myocardium is revascularized must indicate that structural changes are absent or minimal, as had been found in experimental models of stunned myocardium. However, since the early 1980s, it has been known that chronically dysfunctional myocardial segments demonstrate distinct morphological changes that can be verified by both the light and the electron microscope .One prominent feature of the changes seen in cardiomyocytes, by light microscope, is the loss of contractile material, which is replaced with an amorphous, strongly Periodic Acid-Schiff (PAS)-positive material typical of glycogen in addition to variable intracellular fibrosis , 20. TheThe differentiation of viable from nonviable myocardium is therefore highly relevant in patients who are being considered for revascularization . Many paQ waves on the ECG were originally thought to indicate full-thickness myocardial infarction (MI), but in fact, there is no relationship between the presence and extent of Q waves after MI and infarct size assessed by myocardial perfusion imaging, and up to 60% of regions with Q waves have viable myocardium detected by imaging techniques . Fragmennuclear imaging by Positron Emission Tomography (PET) ,nuclear imaging by Single-photon emission-computed tomography (SPECT) ,echocardiography with dobutamine (to assess contractile reserve),echocardiography with intravenous contrast agents (to assess perfusion),in addition, MRI with dobutamine (to assess contractile reserve), and MRI or CT with intravenous contrast agents (to assess scar tissue) are emerging as promising techniques.Ventriculography is the oldest imaging technique and is rarely used clinically today , 35. OthIt is obvious that each of these techniques can detect viability by assessing different factors of the myocardial tissue. The strength of PET as an imaging technique relies on the versatility of positron emitting radionuclides that can be integrated into important biochemical molecules. Not only can the distribution of these molecules be imaged, but their uptake can be quantified. In this way, it is possible to assess myocardial perfusion, glucose utilization, fatty acid uptake and oxidation, oxygen consumption, contractile function, and presynaptic and postsynaptic neuronal activity .Angiotensin converting enzyme (ACE) inhibitors have been radiolabeled and used in experimental systems to study the tissue ACE receptor system directly. Preliminary observations in explanted hearts from patients who had heart failure showed a relationship between binding of [18F]fluorobenzoyl-linsinopril and collagen replacement; ACE was absent in the collagen-stained areas and was increased in the juxtaposed areas of replacement fibrosis . The incSPECT imaging identifies viable and infarcted myocardium based on regional differences in radiotracer uptake, with segments classified as viable as a consequence of preserved mitochondrial function (technetium SPECT) or preserved membrane integrity  .Technetium-labelled tracers have advantages over thallium, such as a shorter half-life with lower radiation exposure to the patient, a higher energy gamma emission that reduces soft-tissue attenuation, more flexibility in imaging times after stress, and the potential for ECG-gated acquisition. However, unlike thallium, technetium tracers have significant redistribution, which necessitates 2 inject ions of the tracer (exercise and rest) for typical stress-rest protocols either on the same day or in two different days . This maTo enhance the ability of technetium SPECT imaging to detect viability, several methods have been used; some are technical  and other included pharmaceutical additives .Recently, Spadafora et al.  proposedThe VIA and REC maps were also represented as 3-D images. On the VIA map, segments with counts <20% of the peak activity were represented in black or dark blue indicating nonviable segments, whereas segments with counts ≥20% were considered hibernated. Similarly, on the REC map, segments with counts <20% of peak activity were represented in black or dark blue indicating regions without functional recovery, and segments with counts ≥20% of the peak were considered as showing functional recovery. The proposed polar map of myocardial viability obtained by gated SPECT imaging accurately predicts functional recovery after coronary revascularization .Bisi et al.  proposedβ-methyl-iodo-pentadecanoic acid (BMIPP) labeled with iodine-123, since it is metabolically trapped in the myocardium due to its methyl branching   , 83.Assessment of resting wall thickness and thickening by resting cine-MRI can be used to assess viability. The underlying hypothesis is that regions of myocardial thinning reflect chronic myocardial infarction. The combination of wall thickness and systolic wall thickening tend to improve the sensitivity and specificity of the technique . Cine-MRDE-MRI can concomitantly detect infarcted and normal myocardium within a given myocardial segment and thereby allows extent of viability to be assessed . The conDE-MRI has been found to be comparable to each of DSE, SPECT, and PET in several studies –93. HoweAlthough using contrast-enhanced CT to assess viability is not new, recent advances in its temporal and spatial resolution with multidetector CT (MDCT) technology have gained interest for this application . Recent Electromechanical endocardial mapping using a nonfluoroscopic catheter-based system (NOGA) was first described in 1996 . BecausePrior studies that evaluated the role of noninvasive imaging techniques in the detection of myocardial viability have focused on several clinical endpoints. These endpoints include: improvement in regional LV function (segments), improvement in global LV function (LVEF), improvement in symptoms , improvement in exercise capacity , reverse LV remodeling (LV volumes), prevention of sudden death (ventricular arrhythmias), and long-term prognosis . Improvement in function after revascularization is still considered the final proof of viability . From thThe proportions of viable segments needed for improvement in the LV EF differed among the studies. The available evidence (mainly using DSE) suggests that 20%–30% of the left ventricle needs to be viable to result in improvement in the LV EF . It is a99 m sestamibi SPECT before OAT randomization, with repeat imaging at 1 year. There were no significant differences in 1-year end-diastolic or end-systolic volume change between those with severely reduced versus moderately retained viability, or when compared by treatment assignment . In multivariable models, increasing baseline viability independently predicted improvement in LV EF (P = .005) but there was no interaction between viability and treatment assignment for any measure of LV remodeling [Another important endpoint in viability assessment is the prediction of LV remodeling, by comparing LV volumes before and after revascularization. Large trials with ACE inhibitors have shown that reverse LV remodeling is associated with improved survival. On the other hand, patients with predominantly scar tissue exhibited adverse LV remodeling, shown as an increase in both LV end-systolic and end-diastolic volumes. Therefore, surgery for patients with predominantly scar tissue did not result in reverse LV remodeling during followup . Udelsonmodeling .In the viability cascade, the areas with preserved response to dobutamine indicate a mild level of damage, which will usually allow adequate restoration of function following revascularization. For presumably more severe levels of damage, myocardial segments may be unresponsive to inotropic stress by dobutamine, but still can take up a significant amount of thallium. This is likely corresponding to a more advanced form of cellular damage, so that only those cellular functions that are strictly essential to cell survival (membrane integrity) are preserved .In a recent meta-analysis, all available studies of regional left ventricular function in patients with ischemic left ventricular dysfunction before and after revascularization were pooled . This anGenerally, the final endpoint in viability studies is the long-term prognosis. Several studies have evaluated the prognostic value of viability in relation to therapy. These studies consistently showed better prognosis in patients who had viable myocardium and were revascularized, suggesting that revascularization stabilizes the unstable substrate of dysfunctional but viable myocardium . Allman It should be noted, however, that medical therapy was not standardized in the studies analyzed by Allman and colleagues  and the Consequently, Camici and coworkers  pooled tIn a prospective study of 167 patients studied with FDG-PET, Desideri et al.  reportedThe Heart failure Revascularization trial (HEART) is a multicenter study of 800 patients with heart failure, LV EF <35% and evidence of CAD who are receiving optimal medical treatment followed for 5 years. The main aim was to determine whether surgical revascularization improves the survival of patients who have evidence of dysfunctional but viable myocardium . Only 13P = 0.003). However, after adjustment for other baseline variables, this association with mortality was not significant (P = 0.21). There was no significant interaction between viability status and treatment assignment with respect to mortality (P = 0.53). The study concluded that although the presence of viable myocardium was associated with a greater probability of survival in patients with CAD and LV dysfunction, however the assessment of myocardial viability did not recognize patients who can benefit from CABG, as compared with medical therapy alone. This finding may reflect the low rates of death among patients with viable myocardium who received medical therapy alone in STICH study (~7% per year), as compared with previously reported rates [In a substudy from STICH trial  601 patied rates .Recently, Gerber et al. studied 144 patients with coronary artery disease and myocardial dysfunction and concluded that detection of functional viable myocardium by DE-CMR is an independent predictor of mortality in patients with ischemic LV dysfunction before revascularization. This observation may be useful for preoperative selection of patients for revascularization .In many of patients with CAD, the extent of remaining viable tissue is of clinical and prognostic significance. It can help to decide between revascularization and cardiac transplantation. Many subjects with heart failure and underlying coronary artery disease have an important amount of viable but dysfunctional myocardium, where myocardium keeps the ability to contract if perfusion improves. The dysfunctional viable myocardium has unique characteristics which form the basis for the different imaging modalities that are currently available for the assessment of myocardial viability. These modalities include different scintigraphic techniques, DSE, and recently MRI and CT modalities. Recent studies showed that the presence of viable myocardium was associated with a greater likelihood of survival in patients with CAD and LV dysfunction, but the assessment of myocardial viability did not identify patients with survival benefit from CABG, as compared with medical therapy alone. Assessment of myocardial viability alone should not be the deciding factor in selecting the best therapy. Whether the method of viability assessment or the underlying myocardial pathology and response, the determinant of optimal and appropriate mode of treatment is still debatable and needs more evidence.


We developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming.Twelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls.min), indexes of LV contractility  and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased.During progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dtProgressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments. Physicians must take care of patients exposed to various types and levels of hypothermia. In severe accidental hypothermia, surviving victims may have an excellent prognosis, even in the most serious cases of hypothermic circulatory arrest ,2. StillOn the other hand, in the context of induced moderate hypothermia being applied as a protective measure during cardiac surgery, or as a therapeutic action to mitigate global brain ischemic injury in survivors after cardiac arrest, cardiovascular side effects from hypothermia seldom cause problems .In awake homoeothermic animals exposure to cold that may lower body temperature is stressful and will lead to strong neuroendocrine activation and an increase in heart rate and blood pressure . There iper se on myocardial function. From studies on isolated dog and rabbit hearts subjected to moderate and severe hypothermia, increased left ventricular (LV) contractility and increased cardiac work have been reported [2+ storage and Ca2+ sensitivity [From experimental hypothermia research results have been somewhat confounding regarding the effect of low body temperature reported ,13. Corereported ; similarreported . In severeported . Likewisreported . On the reported . The issreported . The finsitivity .The cooling mechanism in out-of-hospital accidental hypothermia is by surface cooling, and this approach has also been used to induce therapeutic hypothermia in survivors after cardiac arrest even though core cooling by indwelling vascular catheters has been developed and used over the last years . RewarmiTo our knowledge, no clinical studies have so far described the complete time-course of surface cooling, steady-state hypothermia and surface rewarming on cardiovascular function and other clinically related physiologic variables in either accidental or therapeutic hypothermia.Previous experimental hypothermia studies of surface cooling/rewarming in animals with maintained circulation have been performed using rodents  and dogsThe apparently closer morphologic and physiologic relationship between humans and pigs suggests that a porcine model is more suitable for translational research. We aimed at developing a pig model of hypothermia and rewarming that should be minimally invasive, but give maximum information of cardiovascular function. Paramount in this effort would be the use of an indwelling conductance catheter in the left ventricle to extract pressure-volume and contractility data.Considering animal welfare, we aimed at sedating the pigs deeply, bringing the model close to therapeutic hypothermia as used in human medicine. By avoiding the use of neuromuscular blockers, and by cooling the animals to severe hypothermia, we intended to shed light on aspects of accidental hypothermia as well.max) significantly, and that the depressed cardiac function prevailed during rewarming. We demonstrated that post-hypothermic contractile dysfunction is due to an isolated perturbation of systolic function, whereas diastolic function is restored.The present study reports that hypothermia below 34°C reduced cardiac contractile functional variables  from a native Norwegian stock (norsk landsvin) were used, of whom eight animals were cooled and rewarmed and four animals were kept normothermic as time-matched controls. The animals received humane care in accordance with The Norwegian Animal Welfare Act. The study was approved by The National Animal Research Authority.The animals were placed in pens for two to five days after arrival to the laboratory animal unit. They were fed twice daily and had free access to water at all times.The overall protocol layout is visualized in Figure 2O was applied throughout the experiments . FiO2 was adjusted to maintain PaO2 > 10 kPa, and alveolar ventilation adjusted to keep PaCO2 of 4.5 to 6 kPa uncorrected for temperature (α-stat management). Arterial pressure monitoring and blood sampling were obtained via a femoral artery catheter. A 5F thermodilution catheter  was positioned in the pulmonary artery via the right external jugular vein for pressure monitoring, continuous core temperature recording, cardiac output measurements and for blood sampling. A single dose of 3,000 IU heparin was given after placement of the thermodilution catheter. Via the left carotid artery a 7F dual field, pressure-volume conductance catheter  was positioned in the left cardiac ventricle for continuous pressure and volume monitoring. To obtain intermittent preload reductions a 7F balloon catheter was positioned in the inferior caval vein via the left femoral vein. A 14F urinary bladder catheter was introduced via a lower abdominal incision for continuous monitoring of urinary output.After an overnight fast, anesthesia was induced in the pen by an intramuscular bolus of ketamine hydrochloride 20 mg/kg, midazolam 25 mg and atropine 1.0 mg. After transfer to the animal research operating theatre, a catheter was inserted into an ear vein and a bolus injection of fentanyl 10 μg/kg and pentobarbital-sodium 10 mg/kg was given. After tracheostomy a continuous right external jugular vein infusion of fentanyl 20 μg/kg/h, pentobarbital-sodium 4 mg/kg/h and midazolam 0.3 mg/kg/h along with Ringer's acetate 9 ml/kg/h was started and maintained throughout the experiment, except for the one-hour period at 25°C core temperature. After termination of experiments the animals were killed with 20 mmol potassium chloride given as an intravenous bolus. No neuromuscular blockers were used at any time. Animals were maintained on intermittent positive pressure ventilation and a positive end expiratory pressure (PEEP) of 4 cm HEach data sampling procedure lasted about five minutes and was carried out in the following order: 1) acquisition of electrocardiography (ECG), mean arterial blood pressure (MAP) and central venous pressure (CVP); 2) recording of cardiac output (CO), blood temperature, diuresis and respirator settings; 3) blood sampling from femoral and pulmonary arteries; 4) recording of steady state LV pressure-volume (PV) data, and; 5) recording of PV data during inferior vena cava occlusions. Data sets were collected at baseline, during cooling at core temperatures 34, 30 and 25°C, during maintained hypothermia (25°C) and during rewarming at 30, 34 and 38°C.The conductance catheter placement was guided by LV pressure signals being displayed on a monitor and by advancing the catheter to obtain the maximum number of segments displaying ventricular volumes without causing ventricular arrhythmias. Segments lying outside the ventricle were excluded before each recording. Steady state recordings of PV-loops were performed with the respirator attached. LV contractility at each temperature was determined as the mean value derived from three successive caval occlusions and PV-loop recordings, each time disconnecting the respirator for about 10 sec, and successive respirator attachment and recovery of MAP between occlusions. Data were continuously computed and stored on a Leycom Sigma 5 DF computer  and later analysed by Circlab software . In analysis, conductance derived CO was corrected against CO measured by thermodilution measurements of cardiac output by a thermodilution computer  at each temperature step. In this way, there was no need to correct for temperature dependent blood resistivity (rho), as the thermodilution method is independent from conductance catheter recordings and unaffected by rho. During sampling rho was arbitrarily set at the same fixed value on the Leycom Sigma 5 DF computer at all temperatures.The conductance derived LV end diastolic and systolic volumes (EDV and ESV) resulted from intraventricular conductance and the conductance of surrounding structures, called parallel conductance. Parallel conductance determination by use of repetitive hypertonic (30%) saline infusions at each temperature was not performed, as this would have lead to considerable NaCl accumulation throughout the experiment. Consequently, EDV and ESV in this study do not represent real LV volumes, and no measure of LV ejection fraction could be calculated. However, recording of relative LV volume changes during cooling and rewarming could be performed.max, dP/dtmin), the time constant of isovolumetric relaxation (Tau) based on a monoexponential decay model and LV end diastolic and systolic pressures (EDP and ESP). Preload recruitable stroke work (PRSW), end systolic elastance (Ees) and end diastolic pressure volume relationship (EDPRV) were calculated based on PV recordings during abrupt inferior vena cava occlusions. V0 was defined by the intercept of the Ees slope of the x-axis (volume axis).Steady state readings of conductance data gave, in addition to LV volumes, maximum and minimum values of the first derivate of ventricular pressure over time (dP/dta) was calculated as Ea = LVESP/stroke volume (SV). Arterial-ventricular coupling ratio was determined by Ea/Ees.Arterial elastance . At pre-determined temperatures CO was measured in triplets, by injecting 5 ml precooled saline in the thermodilution catheter positioned in the pulmonary artery. SV and systemic vascular resistance (SVR) were calculated as: SV = CO/HR; SVR = (MAP - CVP) · 80/CO. To index SVR body surface area (BSA) was calculated according to the formula: BSA in m2 = (734 ·Weight 0.656): 10,000 [ECG from standard leads, heart rate (HR), CVP, MAP, and PAP were continuously displayed on a data monitor and intermittently recorded by a computer program designed at our department using the software package LabVIEW : 10,000 .2 and VO2) were calculated as oxygen content in arterial blood · CO, and the difference of arterial and mixed venous oxygen content · CO, respectively.Global delivery and consumption of oxygen , and a heat-exchanger , cold water (5°C) circulated the hollow operating table and a tarpaulin tub surrounding the animal. The upper left side of the animal was covered with ice slush and irrigated by cold water leaving two-thirds of the dependent animal submerged. The head was placed on a cushion and not immersed or covered with ice slush. At 26°C core temperature cold water circulation was discontinued, the tub drained for water and ice slush, and core temperature subsequently dropped to approximately 25°C in all animals. To prevent core temperature from a further drop, small amounts of warm water was added to the tub. Rewarming was achieved by circulating the operating table and the tub, and by irrigating the upper left side of the animal, with hot water  till rewarming (38°C) was accomplished.Blood with heparin (4 IU/ml), reduced glutathione (4.5 mM) and EGTA (5 mM) was kept on ice/water for maximally 30 minutes before plasma was obtained by centrifugation (1.000 × g) for 20 minutes at 4°C. Samples were stored at -80°C awaiting analysis.Plasma samples (1 to 2 ml) were spiked with known concentrations of the internal standard (DHBA = dihydroxy-benzylamine) and added 1 ml 2 M Tris-EDTA buffer (pH 8.7). The catecholamines were adsorbed onto alumina (10 mg). After aspiration of plasma/buffer, the alumina was washed three times with bi-distilled water (1 ml). The catecholamines were eluted from the alumina with a mixture (100 μl) comprising acetic acid (175 mM), sodium bisulfide (9 mM) and EDTA (0.7 mM). After whirling and centrifugation, the aquous phase was aspirated and transferred to the autoinjector .Dopamine, norepinephrine and epinephrine were separated by HPLC  and their concentrations determined with an electrochemical detector . The analyses were performed at ambient temperature with a flow of 1.2 ml/ml.®, R&D Systems, Inc., Minneapolis, MN, USA). Troponin T (TnT), ASAT, ALAT and albumin were analysed by the sandwich method of electrochemiluminescence, UV-test with pyridoxal phosphate activation, and a colorimetric end point method .Hemoglobin (Hb) measurements, and arterial and mixed venous blood gases were analysed on a blood gas analyser  uncorrected for temperature. Blood samples for serum analysis were put on ice, quickly centrifuged and the serum was then quickly frozen and kept at -80°C awaiting analysis. Tumor necrosis factor alpha (TNF-α) was analysed by the quantitative sandwich enzyme immunoassay technique , Richmond, CA, USA). Intragroup comparisons were performed by one-way repeated measures analysis of variance, or by paired sample Student's Immersion cooling to 25°C lasted 125 ± 15 minutes giving a cooling rate of 6.8 ± 0.7°C/h. Rewarming lasted 133 ± 6 minutes, giving a rewarming rate of 6.0 ± 0.3°C/h. The phenomenon referred to as 'afterdrop', a decrease in core temperature after onset of surface warming, was not observed in any pigs. Visible shivering took place in all pigs at the start of cooling, but subsided with progressive cooling and was absent at 25°C. Little, if any, shivering was observed during and after rewarming.es  was statistically indifferent to moderate and severe cooling, as were EDP  concentration Figure  showed as Figure  decreases Figure  and TNF-s Figure  serum comax) significantly, and that the depressed cardiac function prevailed during rewarming. After rewarming we found that post-hypothermic contractile dysfunction is due to isolated perturbation of systolic function, whereas diastolic function is restored.The present study demonstrates that severe hypothermia (30 to 25°C) reduced cardiac contractile functional variables  of depressed myocardial function [es were accompanied with significant increases in V0, which apparently resulted in steep Ees slopes [0 in the present study. In previous experiments in dogs at our laboratory aimed at determining LV cardiac contractility during cooling and rewarming it was concluded that PRSW appeared to be a more robust index of contractility than Ees during hypothermia [The reason why Efunction . The incs slopes . This paothermia .in vivo single beat contractility estimations in pig have been shown to be unreliable and no better than dP/dtmax in predicting LV contractility [One could argue that, in the absence of VCO-derived contractility data at 25°C, single beat estimates of contractility could have replaced traditional deloading variables. However, actility .min, indicating a temperature-dependent slowing of sarcoplasmic reticulum (SR) function that together with elevated intracellular Ca2+ concentration delayed clearance of cytosolic Ca2+. This finding corresponds well with the fact that diastolic Ca2+ extrusion depends mainly on SR Ca2+ pump activity, also during hypothermia [2+ pump is highly temperature dependent (Q10 effect). The passive, late diastolic phase, the filling phase, was less compromised during hypothermia as indicated by a modest increase in EDPVR, or stiffness, in the present experiment. The effects of change in temperature on the SR Ca2+ pump are demonstrated by the return to control of Tau after rewarming.During hypothermia changes in diastolic functional variables were measured. Most prominent was the increase in indexes of isovolumetric relaxation, Tau and dP/dtothermia , and thamin  may imply an early diastolic dysfunction which remained from the hypothermic period. However, Tau and EDPVR returned to pre-hypothermic levels, EDV was statistically unchanged and EDP was even reduced after rewarming. We interpret the post-hypothermic increase in dP/dtmin as resulting from the concomitantly decreased MAP, and suggest that post-hypothermic early, as well as late, diastolic function is normalized after rewarming. This is in accordance with previous findings that diastolic function was restored in post-hypothermic core cooled dogs [The post-hypothermic reduction of dP/dtled dogs  and ratsled dogs .If the post-hypothermic state is characterized by systolic failure with maintained diastolic function, this clearly makes post-hypothermic cardiac dysfunction different from myocardial stunning, where not only systolic, but also diastolic dysfunction is an invariable finding .in vitro was lost when normothermic HR was maintained by pacing during hypothermia [per se leads to decreased LV contractility, and we interpret the increase in HR as a compensatory mechanism whereby the organism normalized CO and DO2 in the presence of a decreased SV. According to Opie (1998), 'LV failure exists (...) when myocardial ejection is impaired because the inotropic state is depressed' [Increasing HR from 80 to 120/minute by pacing in normothermic humans before hypothermic coronary bypass grafting increased LV contractility . When thothermia . Thus, apressed' . Hypothepressed' , as a copressed' . Experimpressed' . In the The post-hypothermic reductions of MAP and SVR open for at least two possible interpretations; either i) we see a variant of the somewhat imprecise term 'rewarming shock', characterized by reduced cardiac function and drop in blood pressure , or ii) a/Ees coupling ratio [a in itself, being the ratio between LVESP/SV, is not a variable solely derived from the vascular system, and as such does encompass more than SVR. Effective coupling of heart to artery may be defined as the optimal transfer of blood from heart to periphery without excessive changes in blood pressure, and it has been reported that an Ea/Ees coupling ratio of 0.6 to 1.2 represents a near optimal relation between work and efficiency [es) is accompanied by high arterial elastance (high Ea), the Ea/Ees is elevated and the unfavorable situation of afterload mismatch occurs [a/Ees was statistically unchanged from baseline. If MAP and SVR had remained unchanged from pre-hypothermic values, Ea would have been increased, possibly leading to an Ea/Ees ratio significantly increased in an unfavorable direction. In our opinion the reduced post-hypothermic SVR, in the presence of reduced LV contractility and SV, does not necessarily express 'rewarming shock', but may imply an optimized arterial-ventricular coupling ratio that together with increased HR facilitates more physiologic CO and DO2.In recent years, an integrated view of the interaction between vascular tone and cardiac contractility has been pursued through the study of the coupling between arterial and cardiac elastance, expressed as the Eng ratio . Ea in ificiency . When syh occurs . In the The low incidence of ventricular fibrillation (VF) in our model may be ascribed as species-specific. However, it is likely that the deep anesthetic state protected against cardiac arrhythmias, as catecholamines, especially epinephrine, from both endogenous and exogenous sources have been proven to illicit VF during experimental surface cooling ,46.There is no evidence in our material that global oxygen consumption at any time was dependent on oxygen delivery. Two facts support this statement: i) oxygen content of mixed venous blood increased during hypothermia, and ii) the difference in oxygen content between arterial and mixed venous blood in the hypothermic animals was no different from time-matched normothermic controls. Previous experiments in our laboratory have demonstrated that increased oxygen extraction from mammalian arterial blood is possible at temperatures as low as 15°C . FurtherIn the present experiments animals shivered during initial cooling and this fact may explain why oxygen consumption was only marginally reduced during this phase of the protocol. In the absence of shivering, the relationship between core temperature and oxygen consumption would probably have been linear rather than taking the observed form of a negative exponential function.The temperature-dependent fluctuations in Hb concentration throughout the experiment could not be attributed to periodic blood loss, as bleeding from instrumentation was minimal and blood sampling was evenly distributed. Also, Hb concentration changes were unrelated to diuresis, as diuretic output was constant throughout experiments. More likely, changes in Hb concentration were caused by fluctuations in plasma volume by other mechanisms, as has been reported in the time course of surface cooling ,49 and r2+ mediated activation of intracellular proteases that degrade troponins in the same manner as has been suggested to take place during myocardial stunning [Animals subjected to cooling and rewarming showed a small, but statistically significant increase in TnT that was not present in time-matched normothermic controls. One may suggest that the observed increase in TnT was due to Castunning .Post-hypothermic increase in TNF-α and reduced plasma albumin concentration in our experiment may indicate activation of inflammatory mediators by cooling-rewarming, as has been shown in both surface- and endovascular - cooling in the same species ,51.et al. refer to 15 victims of severe accidental hypothermia rewarmed by forced air at a mean rate of 1.7°C per hour [A cooling rate of about 6°C per hour, as in the present experiments, is faster than in induced therapeutic hypothermia , but appper hour . Furtherper hour , which iSurface cooling to 25°C followed by rewarming resulted in reduced systolic, but not diastolic, LV function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure.• Cardiac left ventricular contractility decreases during surface cooling below 34°C.• Cardiac systolic function is depressed after rewarming from 25°C.• Cardiac diastolic function is restored after rewarming from 25°C.• Post-hypothermic cardiac output is maintained by increased heart rate.• Decreased post-hypothermic systemic vascular resistance may be adaptive measure.2: global delivery of oxygen; dP/dtmax: maximal acceleration of pressure in the cardiac cycle; dP/dtmin: maximal deceleration of pressure in the cardiac cycle; Ea: arterial elastance; Ea/Ees: arterial-ventricular coupling ratio; Ees: end systolic elastance: slope of the linear ESPVR for a family of PV-loops during VCO; EDP: end diastolic pressure; EDPVR: end diastolic pressure volume relationship; EDV: end diastolic volume: in the present paper consisting of LV end diastolic volume and the volume of surrounding structures; ESP: end systolic pressure; ESV: end systolic volume: in the present paper consisting of LV end systolic volume and the volume of surrounding structures; ESPVR: end systolic pressure volume relationship; Hb: hemoglobin; HR: heart rate; LV: left ventricular; MAP: mean arterial pressure; PRSW: preload recruitable stroke work; PV: pressure-volume; SV: stroke volume; SVR(I): systemic vascular resistance (index); Tau: isovolumetric relaxation time; TNF-α: serum tumour necrosis factor alpha; TnT: serum cardiac troponin T; V0: volume axis intercept of the ESPVR slope determined by PV-loops during VCO; VCO: vena cava occlusion: abrupt occlusion of the inferior caval vein to obtain PV-loops; VF: ventricular fibrillation; VO2: global consumption of oxygen.CO: cardiac output; CVP: central venous pressure; DOThe authors declare that they have no competing interests.OMF conducted the experiments and, together with TT, designed the protocol, discussed the data and wrote the manuscript. OJH took part in protocol and scientific discussions, assisted in carrying out experiments and contributed to the writing process. TK took part in carrying out experiments and processing and interpretation of data. TMG took part in protocol discussions and in carrying out experiments. All authors read and approved the final manuscript.


Background. Diastolic dysfunction is common among dialysis patients and is associated with increased morbidity and mortality. Novel echocardiographic speckle tracking strain analysis permits accurate assessment of left ventricular diastolic function, independent of loading conditions and taking all myocardial segments into account. The aim of the study was to evaluate the prevalence of diastolic dysfunction in chronic dialysis patients using this novel technique, and to identify its determinants among clinical and echocardiographic variables. Methods. Patients currently enrolled in the ICD2 study protocol were included for this analysis. Next to conventional echo measurements diastolic function was also assessed by global diastolic strain rate during isovolumic relaxation (SRIVR). Results. A total of 77 patients were included . When defined as E/SRIVR ≥236, the prevalence of diastolic dysfunction was higher compared to more conventional measurements (48% versus 39%). Left ventricular mass  and pulse wave velocity  were independent determinants of diastolic dysfunction. Conclusion. Diastolic dysfunction is highly prevalent among dialysis patients and might be underestimated using conventional measurements. Left ventricular mass and pulse wave velocity were the only determinants of diastolic dysfunction in these patients. In dialysis patients, both cardiovascular and noncardiovascular mortality are significantly increased as compared to the general population . In partE)/SR ratio during LV isovolumetric relaxation (IVR) period showed to be highly correlated with the invasive measure of pulmonary capillary wedge pressure, and a cut-off value of 236 was able to identify patients with elevated LV filling pressure with high sensitivity and specificity [Recently, LV global diastolic strain rate (SR) measurement by 2D echocardiography speckle-tracking analysis was demonstrated to be superior to the mitral annulus velocities measured by TDI, for the assessment of LV diastolic function, especially in patients with relatively preserved LV ejection fraction (EF) or with LV regional wall motion abnormalities. In particular, mitral early diastolic velocity  were included in the current analysis. The rationale and protocol of this study have been previously reported [9861 wereAll included patients underwent an extensive screening evaluation before randomization to the treatment or control arm of the study. In particular, patients on hemodialysis were evaluated on the day prior to a dialysis session. Information was obtained on medical history and medication use. A physical examination was performed, and EDTA and heparinized blood samples were collected. Transthoracic echocardiography was performed, including conventional and advanced measures of LV diastolic function. Finally, vascular stiffness was assessed by applanation tonometry.All patients were examined in the left lateral decubitus position with a commercially available ultrasound transducer and equipment . The images were digitally stored for off-line analysis .According to standard techniques, a complete 2D, color, pulse- and continuous-wave Doppler echocardiogram was performed. Using Simpson's biplane method , LV voluAs recommended by the American Society of Echocardiography, maximal left atrial (LA) volume was calculated using the ellipsoid model and indexed to body surface area .A) velocity were measured applying pulse-wave Doppler (sample volume = 2 mm) at the tip of the mitral leaflets in the 4-chamber view. Furthermore, TDI was recorded with high frame rate (≥100 frames/second) from the apical 4-chamber view to assess myocardial velocities. Peak annular early diastolic velocity (E′) was measured in 2 annular LV segments  and averaged to calculate the mean early diastolic velocity. The ratio E/E′ was calculated, as a validated estimate of LV filling pressure, and significant LV diastolic dysfunction was defined as E/E′ ≥ 15.0 [Several conventional parameters of LV diastolic function were assessed. Transmitral E-wave velocity, E-wave deceleration time (DT), and late diastolic wave (′ ≥ 15.0 .IVR) was measured as previously described [IVR was measured and averaged from the 3 apical views  in a frame-to-frame basis within the cardiac cycle. The speckles are visible in the standard gray-scale 2D images and are equally distributed within the myocardium. Strain rate during isovolumic relaxation period . All measurements were performed in a quiet, temperature-controlled clinical research laboratory. Measurements were performed following a 10-minute rest in supine position, after a state of constant heart rate and blood pressure was reached.The aortic pulse wave velocity (PWV) was defined as the distance traveled by the pulse wave between 2 recording sites, divided by the passage time. Using sequential tonometry with simultaneous electrographic gating, pulse waves were recoded at the common carotid artery and the femoral artery. Following the measurements, the system software calculated the PWV. This semiautomatic method to assess PWV has been previously validated .Q1, Q3) when nonnormally distributed. Continuous data were compared using unpaired t-test when normally distributed and using the Mann-Whitney U-test when non-normally distributed. Categorical data are expressed as frequencies and percentages and were compared using χ2 test. Correlation between E/SRIVR and baseline parameters was assessed using Spearsmans' rank correlation coefficient. Multiple logistic regression analysis was performed in order to establish the relationship between different parameters and the presence of LV diastolic dysfunction. For all tests, a P value < 0.05 was considered statistically significant. All analyses were performed in SPSS version 18.0.When normally distributed (as assessed by the Kolmogorv-Smirnov test), continuous variables are expressed as mean ± SD and as median  patients. However using more advanced measures of LV diastolic function, the prevalence of significant LV diastolic dysfunction was higher: a total of 37 (48%) patients showed an E/SRIVR ≥ 236.In these patients, echocardiography  revealedE/SRIVR ≥ 236) and without significant LV diastolic dysfunction (E/SRIVR < 236) are summarized in P < 0.05) and diabetes  was higher in patients with LV diastolic dysfunction. These patients were also on hemodialysis more often . Differences in dialysis vintage and history of myocardial infarction did not reach statistical significance.Clinical characteristics for patients with (2 versus 111 ± 34 g/m2). Vascular stiffness was also significantly increased in patients with diastolic dysfunction, resulting in an increased PWV as compared to patients without LV diastolic dysfunction .These groups showed also significant differences in echocardiographic characteristics . LV and E/SRIVR and between PWV and E/SRIVR . In addition, in order to identify potential determinants of LV diastolic dysfunction, logistic uni- and multivariate regression analyses were performed (P = 0.025), hypertension , diabetes mellitus , PWV , RWT , and LVMI  were significant predictors for the presence of LV diastolic dysfunction. The multivariate model included all parameters with a P value < 0.20 in the univariate analysis and demonstrated that PWV  and LVMI  were the only independent determinants of significant LV diastolic dysfunction.Correlation analysis revealed a significant positive relationship between LVMI and erformed . At the The key findings of this study can be summarized as follows: using LV global diastolic SR measurement, the prevalence of LV diastolic dysfunction in dialysis patients with preserved LVEF was approximately 50%. Using conventional echocardiographic methods, this prevalence was lower, indicating a possible underestimation when applying these techniques. In addition, LVMI and PWV were the only independent determinants of LV diastolic dysfunction in this patient group.Cardiovascular disease largely contributes to the poor outcome in dialysis patients, and sudden cardiac death especially has been put forward as an important cause of mortality in this patient group. It has been reported that sudden cardiac death accounts for almost 60% of cardiovascular mortality and is the cause of death in approximately 25% of dialysis patients , 15. TheRecently, it has been demonstrated that LV diastolic dysfunction provides independent and additional prognostic value for long-term mortality and cardiovascular death in patients with end-stage renal disease, above and beyond that of LVM and LVEF . TherefoE/E′ ratio) [E′ has a number of limitations which can affect its accuracy. Firstly, this approach is an approximation of LV global function, assuming that a single or multiple site(s) represent global LV relaxation. However, it is known that even in patients without segmental dysfunction, LV regional differences exist. Particularly in dialysis patients, significant LV diastolic dyssynchrony has been described to be often present [Recent studies evaluating LV diastolic function in dialysis patients used the ratio of early mitral diastolic velocity to early diastolic velocity (′ ratio) , 18. Alt present .E′ occurs during the early phase of LV filling, not only LV relaxation, but also LA pressure has an important impact on its value [Another important limitation of this approach is the potential effect of LA pressure. Since ts value , 21. ThiE/SRIVR can be used to estimate LV filling pressures, with higher sensitivity and specificity as compared to E/E′, particularly in patients with preserved LVEF and in those with regional dysfunction [IVR requires the presence of adequate apical views, and therefore it is not feasible in patients with suboptimal apical windows. In the present study, this measurement was feasible in 92% of the patients.Conversely, global LV diastolic SR might overcome all the abovementioned limitations. This measurement reflects in fact the performance of all LV segments, it is load independent and accounts for the initial LV size. Furthermore, when measured during the IVR period  and expressed in a ratio with the transmitral E wave, it takes into account the mean LA pressure . Recentlfunction . HoweverAmong the clinical and echocardiographic variables assessed in this study, LVMI and aortic stiffness, assessed with PWV, were the only independent predictors for the presence of LV diastolic dysfunction. Therapies preventing further progression of LVMI and/or aortic stiffness might therefore prevent and/or limit the development of LV diastolic dysfunction.Several therapeutic strategies have shown beneficial effect on LVH (limiting progression or even inducing regression), including angiotensin-converting enzyme inhibitor (ACEi) , angioteArterial stiffening occurs normally with aging and also correlates with the prevalence of atherosclerosis . For patAdvanced glycation end product cross-link breakers also have emerged as a potential therapeutic strategy, and it has been demonstrated that cross-link breakers improve arterial compliance, PWV, and pulse pressure in a selected group of patients .E/SRIVR for the identification of significant LV diastolic dysfunction. It should be noted however that Wang et al. recently demonstrated in a validation study that E/SRIVR has significantly higher specificity and sensitivity as compared to more conventional measurements for the estimate of LV filling pressures. Furthermore, this study was primarily designed to assess and describe the prevalence of LV diastolic dysfunction according to an advanced echocardiographic measurement and moreover to establish its clinical determinants, rather than to compare it to more conventional echocardiographic techniques. The patients used in this analysis are patients with a life expectation of at least 1 year, given the nature of the ICD2 study protocol. Therefore the “sickest” patients are being excluded, and therefore the prevalence of LV diastolic dysfunction might be underestimated. Furthermore, due to the relatively low number of patients and relatively short period of follow-up in the ICD2 study, long-term outcome data could not be included. Before the true additional value of this novel technique can be established, also long-term outcome data should be analyzed in future studies.Given the lack of invasive measurements, this study does not allow for definitive conclusions regarding the accuracy of In dialysis patients with preserved LVEF, the prevalence of LV diastolic dysfunction assessed by global LV SR is relatively high and might be underestimated when using conventional echocardiographic techniques. In these patients, LV mass and PWV are independent predictors of LV diastolic dysfunction and could serve as possible therapeutic targets.


A 59-year-old woman presented for evaluation of heart failure. As a child she was known to have a ventricular septum defect which was no longer demonstrated during adulthood. She was normally in good shape but experienced yearly episodes of left-sided lower airway infections. During the last episode her general physician heard an ejection murmur and rales over her lungs. Chest radiography revealed an enlarged heart, a right descending aorta and a prominent left pulmonary artery Fig. . There wA pulmonary artery originating from the ascending aorta is a rare entity. The condition is described in children in whom surgical repair is attempted at an early age in order to avoid pulmonary hypertension , 2. Our Because of a decreased afterload in combination with an increased pulmonary venous return, a doubling of the cardiac output ensued, likely leading to high output heart failure. This 59-year-old patient truly lived with a striking level of cardiac output, which had probably been present during her whole life, even though she had a normal exercise tolerance and played tennis regularly. Therefore, at this point no further treatment was installed. If progressive worsening of the left ventricular function develops, then pneumonectomy or banding of the pulmonary artery can be considered.In a case of unexplained high output heart failure, looking for shunting, even at unexpected places, may be valuable.