Decompensated heart failure may present with severe hypertension in patients with preserved (PreEF) or reduced left ventricular (LV) ejection fraction (RedEF) and is clinically indistinguishable. Previously, we demonstrated that arterial pressure elevation increases LV filling pressures in a canine model of chronic LV dysfunction with PreEF or RedEF. It is not clear whether any differences in hemodynamics, LV volume or performance, or diastolic function can be demonstrated between canines with PreEF or RedEF in response to arterial pressure elevation. We hypothesized that the LV systolic, diastolic, and hemodynamic response to pressure loading would be similar in RedEF or PreEF.We studied 25 dogs with chronic LV dysfunction due to coronary microsphere embolization with RedEF (35 ± 4%) and 20 dogs with PreEF (50 ± 3%). Arterial pressure was increased with methoxamine infusion and hemodynamics and echo-Doppler parameters of LV size, function, transaortic and transmitral pulsed Doppler prior to and with methoxamine infusion was obtained.Though LV filling pressures were similar at baseline, LV size was larger (p < 0.01) and ejection fraction lower in dogs with RedEF (p < 0.001). With methoxamine, there were similar increases in LV size, LV pressures, and index of myocardial performance with the ejection fraction reduced similarly. Diastolic parameters demonstrated similar tau increases, E/A reduction, and diastolic filling shortening in RedEF and PreEF dogs. A similar extent of isovolumic contraction and relaxation times and index of myocardial performance prolongation occurred with pressure loading.Pressure loading in a canine model of LV dysfunction with PreEF and RedEF resulted in similar degrees of LV dilatation, increased filling pressures, and increased index of myocardial performance. Decompensated heart failure is clinically indistinguishable in patients with either preserved or reduced left ventricular (LV) ejection fraction and may be accompanied by elevated arterial pressures. Although systolic dysfunction is often suspected, it is only after noninvasive imaging that the clinician discovers that the ejection fraction may be in the normal range. This may occur in up to 40–50% of patients depending on age and sex and is more common in elderly females with diabetes ,2. In adIt is not entirely clear whether any differences in hemodynamics, LV volume or performance, or LV diastolic function can be demonstrated between canines with reduced or preserved LV ejection fraction in response to a stressor . Although there have been some information in the literature regarding multiple levels of LV dysfunction, the model employed has been "tachypacing" induced heart failure, and the heart has been unloaded or contractile performance improved with dobutamine ,6. LittlWe hypothesized that the hemodynamic, LV volume and functional responses to the stress of pressure loading would be similar in a model of chronic LV dysfunction with reduced or preserved LV ejection fraction and would demonstrate similar elevations of LV filling pressures and volumes associated with similar direction and extent of abnormalities in indices describing diastolic function.The animals used in this study were maintained in accordance with the guidelines of the Committee on Animal Studies at Wayne State University School of Medicine and with the position of the American Heart Association on research animal use. The study was approved by the Wayne State University Animal Investigation Committee. Anesthesia was induced in 45 conditioned mongrel dogs (16–24 kg) with intramuscular morphine sulfate (1.5 mg/kg) and acepromazine (1.1 mg/kg) followed in 15 minutes by 30 mg/kg of intravenous ketamine hydrochloride. Maintenance anesthesia was produced by intravenous morphine sulfate (1.5 mg/kg/hr) and pentobarbital (3 mg/kg/hr). The dogs were intubated and artificially ventilated with a Harvard respirator using room air. Using fluoroscopic guidance, two 7 F high fidelity catheters (Millar Instruments) were introduced via the right carotid artery and advanced to the left ventricle and ascending aorta. A #8 multipurpose Judkins catheter was introduced through a sheath (Cordis) into the right femoral artery and advanced into the left coronary ostium. Continuous electrocardiographic monitoring was performed using lead II. At held end expiration, ECG, LV pressures, dP/dt, and central aortic pressures were obtained at 100 mm/s using an 8 channel physiologic recorder (Gould). Simultaneous 2 dimensional echocardiograms and Doppler were obtained from with the use of a phased array echocardiograph (Aloka). Transesophageal 4 and 2 chamber view with color flow were obtained from a 5 MHz biplane probe placed in the mid-esophagus with both transaortic and transmitral pulsed Doppler recordings were obtained from the LV outflow tract and from beyond the tips of the mitral leaflets in the left ventricle at 100 mm/s.To test our hypothesis we employed a previously described canine model of LV dysfunction using coronary microsphere embolization ,8. In thst 48 hours.LV dysfunction with preserved ejection fraction (PreEF) or reduced ejection fraction (RedEF) was induced by left main coronary artery plastic microsphere injections (50 and 80 micron) (3 M) injected in alternating boluses (1 cc) of 17,500 or 12,500 microspheres every 5–10 minutes until the peak positive dP/dt was reduced by >20% and the LV end diastolic pressure (LVEDP) was >10 mm Hg (for PreEF) or the peak positive dP/dt was reduced by >25% and LVEDP was >13 mm Hg (for RedEF)). Acute LV dysfunction (LV ejection fraction = 45–50% or 30–35%) was produced in 45–60 minutes with only minimal or mild mitral regurgitation . At 2 weeks post embolization, echocardiographic imaging was performed to assess LV systolic function. If the LV ejection fraction was >55% (for PreEF) or 40% (for RedEF), the animals were anaesthetized, intubated, and instrumented as above. Additional embolizations were performed reducing peak +dP/dT an additional 10–20% or until the LV ejection fraction was <50% (for PreEF) or <40% (for RedEF) following 45 minutes of stabilization. At this time, hemodynamics and Echo-Doppler imaging were repeated as above. This limited embolization approach ultimately leads to a chronic model of LV dysfunction and increased LVEDP characterized by patchy myocardial interstitial and replacement fibrosis (7–9) with an ejection fraction in the normal range (>50%) for PreEF or ejection fraction in the moderate dysfunction range (35–40%) for RedEF. Following 45 minutes of stable hemodynamics, the above parameters were repeated. The right carotid and femoral arteries were repaired and the dogs were allowed to recover without any dog succumbing in the PreEF group and 2 dogs in the RedEF group in the 1At 8 weeks post coronary microsphere embolization, the animals in both groups were anaesthetized, intubated, ventilated, instrumented, and imaged as above. Atrial pacing was instituted at least 5 beats above the baseline rate with a PR interval <160 msec. The above hemodynamics, cardiac outputs, echocardiographic imaging and Doppler recordings were obtained after 10 minutes of steady state pacing. Arterial pressure was increased with a methoxamine infusion to increase LV systolic pressure >40 mm Hg. Methoxamine was chosen as it increases arterial pressure without significant change in peak + dP/dT in this model. The above parameters were again obtained. The pacer was turned off and the dogs were permitted to return to their baseline hemodynamic state of chronic LV dysfunction.For all stages and time periods, LV pressures, dP/dt, cardiac outputs, and aortic pressures were measured from the average of 3 consecutive cycles at held end expiration. Peak LV systolic pressure, LV minimal pressure, and LVEDP were measured. The time constant of LV pressure decline (tau) was calculated using the Weiss method (10). A frame-by-frame assessment of LV volumes using transesophageal apical views throughout the cardiac cycle was calculated using the biplane Simpson's rule from the average of 3 determinations. LV foreshortening rarely occurs in the canine as compared to humans. LV end diastolic volume was defined as the largest volume and end systolic volume as the smallest volume. LV ejection fraction was calculated as the difference between end diastolic volume and end systolic volume (stroke volume) divided by end diastolic volume. LV mass was calculated by the area length method. Effective arterial elastance was calculated as LV end systolic pressure/LV end systolic volume.Doppler indices were measured from the average of 3 consecutive cycles at held end expiration. From transmitral Doppler indices, peak rapid filling velocity (E) and peak atrial filling velocity (A) were measured. The rapid filling deceleration time was calculated as the time interval from the peak rapid filling velocity to the time mitral flow decelerated to the zero baseline. The tracing was extrapolated to the zero baseline if atrial filling commenced prior to mitral flow fully decelerating to zero. The length of the diastolic filling period was obtained as the interval from beginning to the end of transmitral spectral tracing. When rapid and atrial filling velocity spectra demonstrated any degree of merging, the onset of atrial filling was defined at the point of the end of the p wave on the ECG. The time from the R wave to the end of the mitral time velocity spectrum and to the onset of the mitral time velocity spectrum (onset of flow) was obtained. The severity of mitral regurgitation was assessed as the ratio of maximal left atrial color flow jet area during systole divided by the simultaneous left atrial area.For all stages and time periods in both groups of dogs, all Index of myocardial performance (IMP) is defined as the sum of isovolumic contraction time and isovolumic relaxation time divided by the LV ejection time ,4,11. Usa = The period of time from the end of transmitral velocity spectrum of 1 beat to the onset of the transmitral velocity spectrum of the next beat. b = LVET is time interval from the onset of the pulsed Doppler transaortic spectrum to the end of the transaortic spectrum.The isovolumic relaxation time (IRT) was measured as R wave to the onset of transmitral velocity spectrum minus the time from the R wave to the end of the aortic spectral tracing. The isovolumic contraction time (ICT) was measured as "a" minus the sum of LV ejection time and IRT.LV pressure-volume composite plots were constructed for each stage and time period from mean LV pressures and LV volumes obtained throughout the cardiac cycle. An estimate of the operational LV chamber stiffness constant at end diastole was calculated using the approach of Marino, et al . EssentiAll calculations were made off-line by the author (SL) and technical assistants (PP and VJ see acknowledgement) blinded to the dates of the studies, name of the dog, and experimental conditions. Intra-observer and inter-observer variability for LV volume was determined by selecting end diastolic and end systolic frames from the echocardiogram of 10 previously studied dogs. Each frame was analyzed 3 weeks apart by 2 observers (see acknowledgement). The average difference for end diastolic or end systolic volume was 2.2 cc's for intraobserver variability and 3.4 cc's for inter-observer variability.All data was expressed as mean ± standard deviation. Differences between a variable among stages was assessed using analysis of variance for repeated measures. If the F statistic (p < 0.05) indicated a significant difference, then Tukey's test was utilized to determine where the significant differences existed. A p < 0.05 was considered significant.Table 1 Table 2 Table 4 In this study we used a chronic canine model of LV dysfunction with elevated LVEDP's induced by coronary microsphere embolization with either a PreEF or RedEF to determine whether a stressor to LV performance would produce differences in hemodynamics, LV volume and systolic performance, and diastolic function. Methoxamine infusion was administered to increase arterial pressure >40 mm Hg above baseline. The effect of arterial pressure elevation on LV volumes, LV filling pressures, parameters of diastolic function, and IMP were determined.This model of LV dysfunction is ideal as the level of LV dysfunction can be titrated based on the dosage of coronary microspheres and the number of different times the procedure is performed . Pressure loading resulted in identical increases in LV filling pressures associated with similar delays in the onset of diastolic filling, shortening of diastolic filling, and increases in isovolumic times. Consequently, LV filling volumes entered a poorly relaxed left ventricle at higher left atrial pressures at the time of mitral opening . ChangesUsing pressure-volume plots, the effect of pressure loading on LV dysfunction has been well described both clinically and experimentally ,13. HowePatients with decompensated heart failure commonly present in the emergency room with marked increases in arterial pressure. It is only after noninvasive evaluation of the LV ejection fraction that clinicians discover that the ejection fraction may be preserved or in the normal range. Heart failure with normal or PreEF has an increased proportion of elderly females and associated hypertension with rates of morbidity and mortality that have been described as either lower or equivalent to patients with RedEF -23. It hStudies attempting to differentiate PreEF from RedEF at the time of acute decompensation have been limited to surveys and registries. As the pathophysiology of this presentation is still not well understood, clinical or experimental trials addressing this issue have not yet been performed. As hypertension appears as an important co-morbidity, it stands to reason that it may participate in its pathogenesis. Reviews of therapy for decompensated heart failure have suggested normalizing blood pressure, diuresis, use of either angiotensin converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, aldosterone inhibitors, and possibly nitrates for therapy -28. ManyFirst, the appropriateness of the coronary microembolization model for the production of LV dysfunction is open to question. As the microsphere model of LV dysfunction results in diffuse fibrotic changes throughout the myocardium, its histopathology bears great similarity to the histopathology seen in hypertensive and diabetic cardiomyopathy ,32, ischSecond, one must raise the question whether pressure loading is the appropriate stressor. Earlier studies using volume loading increased LV size and LV filling pressures but lengthened LV ejection time . PatientThird, as this is an experimental study, the applicability of these findings and relation to humans is always a limitation. The general anesthesia utilized may influence the results, and the results may differ with conscious canines. However, this anesthesia regimen has been used in numerous studies in our laboratory and results in lower arterial pressures and LV filling pressures, which may lessen the impact of our intervention. Nevertheless, the experimental data cited here clearly indicates that there is little hemodynamic difference to pressure loading based on LV ejection fraction. This is clearly paralleled clinically by our experience in the emergency room when patients who are severely hypertensive and present with acute decompensated heart failure. There are few clinical cues as to whether the LV ejection fraction is normal or reduced. The importance of blood pressure control may assume even greater importance in patients with hypertensive heart disease and symptoms of heart failure.Pressure loading in a canine model of LV dysfunction with PreEF or RedEF resulted in similar degrees of LV dilatation, increased filling pressures, and increased IMP associated with similar delays in isovolumic relaxation and contraction despite a larger left ventricle and a lower ejection fraction in the RedEF group.LV: left ventricular; PreEF: preserved ejection fraction; LVEDP: left ventricular end diastolic pressure; RedEF: reduced ejection fraction; E: peak rapid filling velocity; A: peak atrial filling velocity; IMP: index of myocardial performance; IRT: isovolumic relaxation time; ICT: isovolumic contraction time.The authors declare that they have no competing interests.SL designed the study, carried out the experimental protocol, analyzed the data, and wrote the manuscript. DC assisted in the drafting and revising of the manuscript, provided criticism of the results as they pertain to existing literature, and approved the final version submitted.Click here for file


A 24 year old woman presented in her 6th month of her first pregnancy with light headedness and dizziness at rest and imbalance during walking of 2 weeks duration. Her pregnancy has been thus far uncomplicated. Prior to her pregnancy she had been in good health with no medical history or cardiac problems. She was very active, working full time, swimming, and playing softball. On her review of system, the patient reported that her heart rate had always been slow even after strenuous physical activity but denied ever seeing a cardiologist or having an electrocardiogram (ECG). Her family history was negative for any cardiac or connective tissue disorders.Upon presentation, her ECG demonstrated second degree Mobitz type 1 atrioventricular (AV) block with intermittent complete heart block and a ventricular rate of 32 beats per minute. She underwent an echocardiogram which ruled out the presence of any structural cardiac abnormalities. Lyme titers were negative. A presumptive diagnosis of congenital high grade AV block was made.Because she was minimally symptomatic, no further testing was done. She went on to deliver a health baby boy and presented again about 3 months later with chest discomfort, lightheadedness and dizziness but no syncope. Her ECG at that time showed complete heart block with narrow QRS AV nodal escape rhythm at a rate of 30 beats per minute . In viewThree days later, she presented again with pleuritic chest pain. Her pacemaker was interrogated and found to be functioning normally with no extracardiac skeletal muscle stimulation at high outputs in both the atrial and ventricular channels. In the electrophysiology laboratory, the pacing leads were inspected under fluoroscopy and were both found to be within the cardiac silhouette. An echocardiogram showed no pericardial effusion but revealed a hypokinetic left ventricular distal septum, anterior wall, and apex with an ejection fraction of 45-50 %. As the chest discomfort continued, a CT angiography of her coronary arteries was performed which showed no disease, but revealed a possible microperforation of the right ventricular lead. The patient was taken back to the electrophysiology laboratory where her right ventricular lead was repositioned in the high interventricular septum. Within 24 hours of the procedure, the patient's symptoms of pleuritic chest pain resolved. Serial echocardiograms up to 6 months after her pacemaker implantation, showed persistence of the area of septal, apical, and anterior hypokinesis with mild decrease in systolic function.We present a case of a patient who presented 6 months into her first pregnancy with complete heart block presumably from congenital heart block that may have gone unnoticed for the first 24 years of her life, and who was also diagnosed with an apical cardiomyopathy 3 months after delivering her baby. This case raises a number of interesting questions. First, are the complete heart block and the cardiomyopathy two separate entities that happened to coexist in this young lady or are they related in the sense that the complete heart block could have been an early manifestation of the cardiomyopathy? Second, what is the mechanism of the cardiomyopathy in this patient? Is it a stress-related apical hypokinesis  related Unfortunately, there is no test that can be done to ascertain the answer to these important questions. The fact that the patient had always had slow heart rates and that she was minimally symptomatic at presentation supports a diagnosis of congenital complete heart block  particularly that the Lyme titers were negative. The level of the AV block is presumably in the AV node, as suggested by the narrow escape QRS complex, is also consistent with congenital heart block.The etiology of the cardiomyoathy is also difficult to confirm. What is clear is that at the time of her initial presentation, 6 months into her pregnancy, the patient had a normal left ventricular function without any regional wall motion abnormalities. Three months after delivering, she had evidence of an apical hyopkinesis which persisted for more than 6 months after delivering the baby and for about 3 months after it was originally detected. This time course is inconsistent with the diagnosis of Takotsubo in which all regional wall motion abnormalities resolve usually within 2 weeks of the stressful event. The fact that the cardiomyopathy was not present 6 months into the pregnancy and was diagnosed after delivery in the context of looking for any evidence of pericardial effusion is suggestive of an unusual form of focal myocarditis or postpartum cardiomyopathy. If this, in fact, is the case, then this finding suggests that possibly many cases of mild post-partum cardiomyopathy or myocarditis are missed after otherwise uneventful pregnancies and deliveries.Finally, although pacing of the heart alters the electrical and therefore the mechanical activation of various parts of the ventricles, it almost never causes a regional wall motion abnormality that persists for months after the lead position is changed.In summary, we present a case of complete heart block of probable congenital etiology in a pregnant 24 year old patient who developed a new apical left ventricular dysfunction after delivering her baby. Although cases of congenital heart block and of left ventricular dysfunction developing in the post-partum period have been reported in the literature, to our knowledge, this is the first case of both these two entities coexisting in the same patient. Common clinical or genetic predispositions to these two findings may exist but cannot be ascertained at the present time.


The G protein-coupled estrogen receptor (GPER) is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist  or vehicle  on cardiac function and structure.Intact female mRen2.Lewis rats were fed a normal salt  diet or a high salt  diet for 10 weeks beginning at 5 weeks of age.Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV) diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope), increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e′)] independent of prevailing salt, and improved the e′/a′ ratio in HS versus NS rats (P<0.05) as determined by tissue Doppler.Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure. Hypertension in postmenopausal women results in left ventricular hypertrophy (LVH), a major causative factor for reductions in both myocardial relaxation and diastolic compliance which are key components of diastolic dysfunction Estrogen attenuates the development of cardiac hypertrophy and fibrosis through activation of steroid receptors ERα and ERβ located on myocytes, fibroblasts, and the extracellular matrix Our recent studies find that chronic treatment with the selective GPER agonist G-1 significantly reduces hypertension in the estrogen depleted mRen2.Lewis congenic rat ad libitum access to rat chow and tap water.Female mRen2.Lewis rats were obtained from the Hypertension and Vascular Research Center Congenic Colony of Wake Forest University School of Medicine and all studies were approved by the institution's Animal Care and Use Committee under protocol #A08-198. Rats were individually housed in an Association for Assessment and Accreditation of Laboratory Animal Care-approved, temperature (22±2°C) and light (12 h light/dark cycle) controlled facility with The mRen2.Lewis rats were fed either a normal salt  or high salt  diet  for 10 weeks starting at 5 weeks of age. The percentage of sodium was chosen based upon its known effects on cardiovascular pathogenesis in the mRen2.Lewis female rat, as originally determined The pressures were recorded in pre-trained rats while lightly restrained and warmed (35°C). At the end of the 2-week treatment period, left ventricular dimensions and left ventricular function were assessed by M-mode and Doppler echocardiography, respectively. Once the experiments were terminated, the hearts were removed and weighed with a portion being submerged in 10% formalin for histology.3 – LVEDD], where 1.04 is the specific gravity of muscle. Relative wall thickness (RWT) was calculated as: 2× PWT/LVEDD. Mitral inflow measurements of early filling velocity (Emax), deceleration slope of early filling velocity (Edec slope), and deceleration time of early filling flow velocity (Edec time) were obtained using pulsed Doppler, with the sample volume placed at the tips of mitral leaflets from an apical four-chamber orientation. The following measurements were made from the septal mitral annular velocity by tissue Doppler imaging (DTI): early diastolic (e′), late diastolic (a′), and the ratio, e′/a′. The early filling velocity-to-early mitral annular velocity ratio (E/e′) was used as a measure of filling pressure. All measurements were performed with an off-line analysis system  by the masked investigator. An average of at least five consecutive cardiac cycles to minimize beat-to-beat variability was used for all measured and calculated systolic and diastolic indices.Echocardiography of all animals was performed at the end of week 15 using a Philips 5500 or Envisor CD echocardiograph  and a 12 MHz phased array probe. All measurements were made in accordance with the conventions of the American Society of Echocardiography, and were conducted by the same investigator who was blinded to the experimental groups. For the procedure, animals were lightly sedated with 4% isoflurane, and then maintained at 2.0% isoflurane. Left ventricular end-diastolic and end-systolic diameters , LV posterior wall thickness (PWT), and anterior wall thickness (AWT) were measured from midpapillary, short-axis images obtained by M-mode echocardiography. The percentage of LV fractional shortening (%FS), an index of contractile function, was calculated as FS (%)  =  [(LVEDD – LVESD)/LVEDD]×100. LV mass was calculated using a standard cube formula, which assumes a spherical LV geometry according to the formula: LV mass (LVmass)  = 1.04×[[LVEDD + PWT + AWT]Heart specimens were fixed for 24 h in 10% formalin, then dehydrated in graded ethanols and embedded into paraffin blocks. 4 µm sections were mounted on positive-charged slides and stained with Picrosirius red (PSR) to evaluate collagen deposition within the tissue. Images of interstitial and perivascular collagen were captured using both bright-field and polarized dark-field microscopy in order to clearly differentiate the Sirius red bound collagen from other cellular structures Heart sections mounted on slides were blocked with 0.1% Tween, 1% bovine serum albumin, and 5% normal donkey serum. Anti-GPER  was diluted 1∶250 in blocking buffer and incubated overnight at 4°C. For a negative control, the primary antibody was pre-incubated with the blocking peptide for 1 h at 25°C and centrifuged before being applied to tissue sections. Biotinylated goat anti-rabbit  was diluted 1∶400 in the blocking buffer and applied for 1 h at 25°C. Antibody binding was detected using Vectastain Elite avidin-biotin complex kit (VectorLabs) and 0.1% diaminobenzene . Slides were counterstained with hematoxylin .www.ncbi.nlm.nih.gov/Genbank) sequences and confirmed with OligoAnalyzer 3.0 . Total RNA was extracted from frozen, pulverized left ventricular tissue from each rat using TRIzol Reagent  and processed according to the recommendations of the manufacturer. The quality and quantity of RNA samples were determined by spectrometry and agarose gel electrophoresis. Complimentary first strand DNA was synthesized from oligo (dT) primed total RNA using the Omniscript RT kit . Relative quantification by real-time PCR was performed using SYBR Green PCR kit . Amplification and detection were performed with the use of the ABI7500 Sequence Detection System (Applied Biosystems). PCRs were carried out in duplicate. Only one peak from the dissociation curve was found from each pair of oligonucleotide primers tested. In each PCR run, a no-template-control was included to check for any contamination disturbing PCR. It was also confirmed that no amplification occurred when samples were not subjected to reverse transcription. Sequence-specific oligonucleotide primers were designed according to published GenBank  with P<0.05 considered statistically significant.All values are expressed as mean ± SEM. Blood pressures were analyzed by two-way ANOVA, followed by the Bonferroni post-As previously reported Two-weeks of the GPER agonist G-1 infusion in either the HS or the NS group did not significantly alter systolic blood pressure [G-1: F = 3.88, P = 0.064), despite the fact that the HS diet markedly exacerbated systolic hypertension in comparison to NS . The lacThe effects of HS on cardiac hypertrophy and body weight change, in the presence or absence of G-1, are shown in Long-term HS significantly increased interstitial and perivascular collagen deposition as measured by Picrosirius Red staining . The incLeft ventricular wall dimensions and systolic parameters are summarized in In addition to salt-associated changes in cardiac geometry, diastolic parameters were also negatively affected by the HS diet . Conventin vivo activation of the novel receptor GPER in the female mRen2.Lewis rat, a congenic rodent model of salt-sensitive hypertension and early diastolic dysfunction To our knowledge, this is the first study investigating the cardiac structural and functional effects of Chronic high salt intake stimulates structural changes in the left ventricle through pressure overload and via direct myocardial effects Estrogen retards the progression of hypertension Estrogen's anti-remodeling effects also involve its actions on fibroblasts and the cardiac extracellular matrix, composed primarily of collagen proteins. A shift in fibrillar collagen from type III (“youthful” collagen) to type I, for example, is the primary determinant of LV diastolic stiffness dec time), which is indicative of reduced LV compliance Consistent with our earlier study, salt-loading in the estrogen-intact mRen2.Lewis rat resulted in early diastolic dysfunction Along with its anti-remodeling action, the GPER agonist enhanced myocardial relaxation. Late administration of G-1 increased early mitral annular descent (e′) in NS and HS mRen2.Lewis rats. While reductions in vascular stiffening and lessening of hypertension can enhance diastolic function, systolic blood pressures were not overtly reduced by G-1 in this study. The increased e′ to a′ ratio further corroborates the direct lusitropic action of G-1 in the HS females. Importantly, an e′ to a′ ratio >1.0 is considered normal, with a reduced ratio (as in the HS vehicle group) indicating impaired early diastolic relaxation The lack of an obvious effect of G-1 on blood pressure in the present study can be attributed to the presence of the endogenous ligand for GPER, estradiol. Although we did not assess circulating 17-β estradiol in the current study, we previously reported that serum estrogen levels are not changed with chronic salt loading A few limitations can be identified in this study. Although we found statistically significant differences in functional and structural outcomes, particularly early mitral annular descent and relative wall thickness, respectively, one potential concern is that our study may have been underpowered to reliably detect the effects of G-1 on blood pressure. Limited pilot data for a priori power analysis using G-1 under high salt conditions existed. Nevertheless, to place the differences in context, we observed a 28% increase in systolic blood pressure between salt conditions. Whereas, the G-1 differences in blood pressure ranged between −8% to 6% over the treatment period. These differences are unlikely to be clinically relevant even with a larger sample. Certainly, noninvasive blood pressure monitoring is less sensitive than radiotelemetry. However, this methodology was first validated in the early 1970s Taken together, these data provide the first evidence for a cardioprotective role for GPER in the hypertensive, salt-sensitive female mRen2.Lewis rat. Activation of this novel estrogen receptor attenuated diastolic dysfunction and cardiac hypertrophy in hypertensive female rats without requisite reductions in blood pressure. Given the lack of adequate therapeutic strategies for the treatment of diastolic dysfunction in females, targeting of GPER may elicit estrogenic benefits in the cardiovascular system. Clinically, GPER activation may offer a new hormone replacement approach providing less adverse effects than traditional therapy targeting all estrogen receptors.


To examine relationships between severity of echocardiography (echo) -evidenced diastolic dysfunction (DD) and volumetric filling by automated processing of routine cine cardiovascular magnetic resonance (CMR).Cine-CMR provides high-resolution assessment of left ventricular (LV) chamber volumes. Automated segmentation (LV-METRIC) yields LV filling curves by segmenting all short-axis images across all temporal phases. This study used cine-CMR to assess filling changes that occur with progressive DD.80 - proportion of diastole required to recover 80% stroke volume). Echo was the reference for DD.115 post-MI patients underwent CMR and echo within 1 day. LV-METRIC yielded multiple diastolic indices - E:A ratio, peak filling rate (PFR), time to peak filling rate (TPFR), and diastolic volume recovery . PFR by CMR increased with DD grade, similar to E/e' (p < 0.001). Prolonged DVR80 identified 71% of patients with echo-evidenced grade 1 but no patients with grade 3 DD, and stroke-volume adjusted PFR identified 67% with grade 3 but none with grade 1 DD (matched specificity = 83%). The combination of DVR80 and PFR identified 53% of patients with grade 2 DD. Prolonged DVR80 was associated with grade 1  with a similar trend for grade 2 , whereas high PFR was associated with grade 3  DD.LV-METRIC successfully generated LV filling curves in all patients. CMR indices were reproducible (≤ 1% inter-reader differences) and required minimal processing time . CMR E:A ratio decreased with grade 1 and increased with grades 2-3 DD. Diastolic filling intervals, measured by DVRAutomated cine-CMR segmentation can discern LV filling changes that occur with increasing severity of echo-evidenced DD. Impaired relaxation is associated with prolonged filling intervals whereas restrictive filling is characterized by increased filling rates. Left ventricular (LV) diastolic dysfunction (DD) has important consequences following acute myocardial infarction (MI) as heart failure and mortality risks are linked to severity of diastolic impairment -3. DD alCardiovascular magnetic resonance (CMR) is a standard for LV chamber volumes and ejection fraction (EF) based on quantification of cine images acquired at end-diastole and end-systole ,12. CineThe current study employed LV-METRIC among a broad post-MI population with variable systolic function. In all patients, dedicated echo imaging was prospectively done within one day of CMR to provide a uniform reference for diastolic performance. The aim of this study was to test whether automated segmentation of routine cine-CMR can discern LV filling changes that occur with graded severity of diastolic impairment.The population comprised consecutive patients enrolled in a post-MI imaging registry  who underwent CMR and echo within one day. Patients were excluded if echo characterization of diastolic performance was incomplete due to absence of tissue Doppler or pulmonary vein inflow patterns (n = 6), arrhythmia prohibiting echo/CMR assessment of LV filling (n = 2), or intolerance of CMR (n = 1). No patients were excluded based on clinical characteristics or CMR processing results.To minimize the impact of post-MI stunning and transient volume shifts on LV performance , imagingTransthoracic echoes were performed using commercial equipment . Echo measurements, adjudication of diastolic filling patterns, and classifications of diastolic grade were made by an experienced echocardiographer (RBD) blinded to CMR results. Mitral inflow parameters and tissue Doppler profiles were acquired in an apical 4-chamber view. Linear measurements of chamber size and systolic function were performed in accordance with consensus guidelines . DD was Normal: E/A ≥ 0.8, septal e' ≥ 8 cm/s, lateral e' ≥ 10 cm/s, deceleration time (DT) 140-240 msec• Grade 1 (mild): E/A < 0.8, septal e' < 8 cm/s, lateral e' < 10 cm/s, DT > 240 msec• Grade 2 (moderate): E/A 0.8-1.5, septal e' < 8 cm/s, lateral e' < 10 cm/s, DT 140-240 msec• Grade 3 (severe): E/A ≥ 2, septal e' < 8 cm/s, lateral e' < 10 cm/s, DT < 140 msec• In patients with equivocal tissue Doppler indices , e'/a' reversal (< 1) and pulmonary vein profiles were used to establish presence of DD ,5.CMR was performed using 1.5 Tesla scanners . Cine-CMR used a commercially available 2D steady state free precession pulse sequence. Images were acquired in contiguous short-axis slices from the mitral annulus through the LV apex. Typical parameters were repetition time 3.5 msec, echo time 1.6 msec, flip angle 60°, in-plane spatial resolution 1.9 mm × 1.4 mm, slice thickness 6 mm, inter-slice gap 4 mm, reconstructed temporal resolution 36.5 ± 9.2 msec. Delayed enhancement CMR (DE-CMR) was performed in all patients for assessment of LV infarct size.Automated quantification of LV volumes and myocardial mass was performed using LV-METRIC. User input included identification of the slice range to be segmented and definition of the mitral and aortic valve annulus. Optional corrections comprised manual contouring to restrict region-growth and adjusting blood sensitivity. LV volumes were quantified as the sum of short axis chamber volumes (2D area * slice thickness) measured during end-diastole (EDV) and end-systole (ESV). Ejection fraction (EF) was calculated as EDV-ESV]/EDV*100. Automated border detection of end-diastolic endocardial and epicardial contours quantified LV mass, calculated as the product of myocardial volume and specific gravity ([EpiEDV-EDV]*1.05) .CMR images were analyzed to quantify other structural indices that can impact LV diastolic performance. Left atrial volume was quantified in accordance with guidelines for biplane chamber planimetry . LV wallLV-METRIC segmentation was performed for all LV short-axis slices across all temporal phases Figure  to assesPeak Filling Rate [PFR] - maximal LV filling rate defined by maximal change in LV volume between sequential temporal phases (Δ volume/Δ phase). This index was also normalized for LV stroke volume [nPFR]• Time to Peak Filling Rate [TPFR] - time interval between end-systole and peak filling rate• Diastolic 80% Volume Recovery [DVR80] - proportion of diastole required to recover 80% LV stroke volume, a cutoff based on prior validation data [• ion data Figures Comparisons between groups were made using analysis of variance (for multiple group comparisons) or Student's t-test for continuous variables, with results expressed as mean ± standard deviation. Categorical variables were compared using the Chi-square test. Bivariate correlation was employed to evaluate associations between continuous echo and CMR parameters. Multinomial logistic regression was used to assess relations of CMR parameters to echo DD grade. Two-sided p < 0.05 was considered indicative of statistical significance. Statistical calculations were performed using SPSS 12.0 .The population consisted of 115 post-MI patients who underwent echo and CMR within a one day interval (97% same day); 65% had echo-evidenced DD. Diastolic dysfunction was mild (grade 1) in 28% (n = 21), moderate (grade 2) in 60% (n = 45), and severe (grade 3) in 12% (n = 9) of affected patients.As shown in Table LV-METRIC successfully generated filling curves in all cases, yielding multiple diastolic parameters Table . Figure 80, TPFR, and PFR. Mean processing time was 2:09 ± 0:51 minutes for the initial reader (175 ± 34 images per exam), with similar processing time (2:15 ± 0:50) for the second reader (p = 0.12).Repeat LV-METRIC processing was performed in 30 sequential patients to assess reproducibility .Table 0 Figure  manifestE:A filling ratios by CMR and echo Table  also yie80  and lower PFR  when compared to normals.Among patients with echo-evidenced grade 2 DD, cine-CMR demonstrated E:A ratios > 1 in 68% . For echo, magnitude of E:A ratios was similar between patients with grade 2 DD and normal diastolic filling . For cine-CMR, E:A ratios were slightly lower among the DD group , consistent with decreased volumetric filling during early diastole. As further evidence of impaired early diastolic filling, patients with grade 2 DD had longer DVR80, the previously established normative threshold of < 77% diastole (to recover 80% stroke volume) was applied based on our prior research among controls with normal systolic/diastolic function [80.To evaluate diagnostic performance of CMR indices in relation to echo DD severity, parameters were tested among each discrete group of echo-assigned diastolic grade and the common group of patients with normal echo-evidenced diastolic filling. For DVRfunction . For all80 yielded a sensitivity of 71% for patients with grade 1 but did not identify any patients with grade 3 DD  of affected patients.Diagnostic performance of CMR indices varied according to graded severity of echo-evidenced DD. DVRDD Table . ConversDD Table . Whereas80 was associated with presence of grade 1  with a similar trend for grade 2 , whereas high PFR was associated with grade 3 DD .Consistent with diagnostic performance results, multinomial logistic regression demonstrated that prolonged diastolic filling intervals and increased diastolic filling rates were associated with different aspects of echo-evidenced diastolic dysfunction. As shown in Table 80), and filling rates (PFR) paralleled echo findings relative to DD grade. Diastolic filling (DVR80) was prolonged in patents with grade 1 and shortened with grade 3 DD, paralleling echo-evidenced DT. Diastolic filling rates  increased with DD grade, similar to E/e' by echo. At matched specificities of 83%, DVR80 identified 71% of patients with grade 1 but no patients with grade 3 DD, while nPFR identified a similar proportion (67%) with grade 3 but no patient with grade 1 DD.This study demonstrates that automated processing of routine cine-CMR can discern physiologic changes that occur with graded severity of DD. LV-METRIC generated LV filling curves within an average processing time of 2 minutes and yielded highly reproducible indices. Diastolic filling ratios (E:A), timing intervals  were prolonged in grade 1 and correlated with echo-evidenced DT. PFR was increased and TPFR decreased among patients with grade 3 DD, consistent with augmented early diastolic filling in restrictive physiology.Diastolic indices generated by LV-METRIC were concordant with established concepts regarding filling changes that occur with graded DD severity ,22,23. FLV filling indices derived from invasive angiography and radionuclide imaging have been used to assess diastolic performance -10,24. COur results extend upon prior studies that have demonstrated feasibility of DD assessment by cine-CMR. Maceira et al reported age-associated decrements in PFR among a normative cohort . However80, TPFR, PFR). Second, while LV-METRIC is a novel segmentation algorithm, the actual cine-CMR data required is a standard component of nearly all clinical CMR exams and requires no tailored pulse sequences or imaging hardware. This enables our approach to be widely applied to both prospective and pre-existing exams. Our prior study demonstrated feasibility among a retrospective dataset of patients with normal systolic function [While multiple techniques can be used to assess LV filling, there are several potential advantages to cine-CMR. First, unlike radionuclide imaging, CMR entails no ionizing radiation and is thereby well-suited for serial assessment of diastolic performance. Our results demonstrated that cine-CMR indices were highly reproducible, with ≤ 1% inter-reader differences for multiple parameters ; nPFR: normalized peak filling rate (stroke volume adjusted); TPFR: time to peak filling rate; DVR: diastolic volume recovery;The authors' institution has submitted a patent for the automated segmentation algorithm (LV-METRIC) described in this study.DDM participated in the study's design and coordination, image analysis, data collection, and manuscript preparation. NCFC and YW developed the automated CMR segmentation software (LV-METRIC) used for image analysis. SS, KK, SJM, JKM, TML, MRP and RBD contributed to image/data analysis and study design. JWW conceived of the study, participated in its design and coordination, and drafted the manuscript. All authors read and approved the final manuscript.


In less than two decades, first-pass perfusion cardiovascular magnetic resonance (CMR) has undergone a wide range of changes with the development and availability of improved hardware, software, and contrast agents, in concert with a better understanding of the mechanisms of contrast enhancement. The following review provides a perspective of the historical development of first-pass CMR, the developments in pulse sequence design and contrast agents, the relevant animal models used in early preclinical studies, the mechanism of artifacts, the differences between 1.5T and 3T scanning, and the relevant clinical applications and protocols. This comprehensive overview includes a summary of the past clinical performance of first-pass perfusion CMR and current clinical applications using state-of-the-art methodologies. This agent reversibly binds to albumin in the plasma, effectively resulting in a macromolecular, intravascular MR contrast agent. While intravascular gadolinium-based contrast agents were initially developed for MR angiography, several groups have identified advantages of these agents for first-pass perfusion imaging -14.To test new contrast agents and validate new imaging sequences, phantoms and animal models of human cardiovascular disease are often employed. First-pass perfusion imaging of the heart using contrast agents on clinical scanners has only been performed in larger animals, e.g., dogs, sheep, and pigs, due to their lower heart rates and larger cardiac size than murine models.When considering animal models for human cardiovascular disease, one of the biggest concerns is whether the degree of collateral circulation mimics man. Maxwell et al. demonstrated that dogs and cats possess the greatest coronary collateral flow after acute ischemia, with pigs possessing the least, and rats, rabbits, and sheep intermediate between dogs and pigs. There aThe imaging pulse sequence is critical in determining the image contrast, spatial resolution, and coverage and influences the potential for quantification and/or the presence of artifacts. This section reviews the basics; a more comprehensive review of perfusion imaging sequences was recently published by Kellman and Arai . The basTo provide T1 contrast, inversion recovery (IR) was the first contrast preparation to be used, but was limited to one or a few slices and proved sensitive to heart rate variation. Saturation recovery (SR) has emerged as the current standard because contrast is theoretically independent of the magnetization "history," e.g., heart rate and previous acquisitions, and a higher numbers of slices (such as six to eight) can be provided with interleaved acquisitions. SR is typically implemented using a non-selective 90 degree radiofrequency (RF) excitation followed by a gradient crusher. This approach can be sensitive to variations in the transmitted RF field, which hCoverage of relevant myocardial segments is achieved using an interleaved acquisition of arbitrarily oriented slices. In Figure In multislice perfusion imaging, the slice thickness is typically 5 to 10 mm, and in-plane resolution is typically 1.5 to 3 mm. Depending on the resolution, field-of-view (FOV), and use of acceleration, image acquisition of each slice can take on the order of 50 – 200 ms. This requires an ultra-fast acquisition, usually based on gradient echo (GRE), gradient echo-planar (GRE-EPI),24, or bth or 1/20th the dose) prior to the full-dose injection used for the measurement of myocardial enhancement and 2) the "dual-sequence" method . Ho. Ho37]. Usually the perfusion sequence is acquired at rest and stress. The DRA may be altered by faster cardiac motion and a more concentrated Gd bolus due to increased cardiac function at stress, leading to increased left ventricular (LV) blood pool signal and more artifact at the margin of the blood pool. However, the rest scan should not be taken as a guarantee against DRA. The effect of residual contrast agent in the second perfusion series should also be considered.Several possible causes have been suggested for DRAs. Di Bella et al . and othThe work done by Arai, Fenchel Banding artifacts at tissue boundaries may occur when the object moves between the acquisitions of different phase encode lines and could be another possible origin of the DRA . ParalleAnother possible origin for DRA is the non-uniform raw k-space data weighting in the phase-encode direction, i.e., signal variations during the acquisition . DistortPartial volume effects may also produce a DRA at the border between the LV blood pool and the endocardium. Using an inversion recovery preparation at certain inversion delays, the phases of both tissues can be opposite, resulting in signal cancellation at this boundary. However, this artifact would be expected to appear around the entire border ,40. A laThe most frequently used pulse sequences for myocardial perfusion studies have been studied to determine which are most prone to DRA. Elkington et al. comparedRecently, Klem et al. described a method for diagnosis of coronary artery disease (CAD) where adenosine-stress and rest perfusion cardiovascular magnetic resonance (CMR) are combined with late gadolinium enhancement (LGE) CMR . This meAlthough DRAs represent the most serious artifact in myocardial perfusion imaging, several other types of artifacts may also occur. Semiquantitative and quantitative analyses of myocardial perfusion studies assume a perfect magnetisation preparation; qualitative analysis will also improve with a complete saturation. Saturation pulses are, in general, not perfect, due to B0 and B1 field inhomogeneities, leaving regional magnetisation residues that alter the apparent T1 relaxation times and eventually lead to errors in quantifying perfusion in those areas. Kim et al evaluateA common artifact seen in perfusion studies is wrap artifact, where one part of the anatomy might be encoded in the same position as another, creating signal interference. Several solutions exist, such as in-plane rotation of the phase/frequency encode direction or increasing the phase-encode field of view. Parallel imaging techniques can also produce artifacts, particularly spatially variant noise, which is related to the position of the coils on the patient, and aliasing due to errors in the sensitivity estimation of the coils. Chemical shifts and N/2 artifacts can also be problematic for GRE-EPI sequences. Therefore these sequences usually incorporate fat suppression pulses and phase correction reference scans, respectively.Whole body 3T scanners are increasing in availability, prompting comparison between 1.5T and 3T for CMR. Higher field strengths have the advantage of higher SNR, but there are also a number of possible disadvantages that could lead to artifacts in perfusion imaging. Firstly, both the B0 and B1 field inhomogeneities are increased and greater care has to be taken to reduce the impact of these. Secondly, the T1 is increased and this, coupled with a shorter T2*, could lead to a reduced signal and perfusion contrast. The relaxivity of the commonly used Gd-DTPA is 3.7 mmol/L/s at 3T versus 4.1 mmol/L/s at 1.5T; therefore, the T1 shortening effect of the contrast agent is reduced at 3T. Nevertheless, precontrast T1 is higher for higher fields, making the difference of T1 before and after contrast larger for high fields and enabling an overall better contrast to noise ratio (CNR) for myocardial enhancement ,47. HoweAn SNR increase of 109% was obtained by Gutberlet et al. using a T1-weighted segmented EPI with an echo train length of 4 at 3T when compared to 1.5T . Araoz eSNR increase comes with the penalty of an increase in the artifact-to-noise ratio (ANR). Artifacts that were already present at 1.5T become more prominent at 3T, such as errors in parallel imaging and a deficient crusher gradient . An incrAnother current problem with high-field systems is the fact that imaging parameters, RF pulse profiles, and RF coil designs have been extensively optimized at 1.5T whereas 3T optimization is now only being performed,52 As 3TCurrently, the two major clinical indications for use of MR perfusion imaging are: 1) the detection and sizing of microvascular obstruction in patients after acute myocardial infarction, and 2) the detection of ischemia in patients with suspected coronary artery disease. In both cases, perfusion imaging pulse sequences will likely be used in combination with other pulse sequences, such as segmented k-space cine sequences to allow assessment of myocardial function, and inversion recovery sequences to allow assessment of myocardial viability. However, since the clinical objectives of CMR in these two groups of patients are different, most investigators will use different study protocols for each type of patient. Also, the image parameters for each group of patients will likely differ to accommodate for the different requirements in these two clinical situations.In patients with acute MI, the main purpose of myocardial perfusion imaging is the precise estimation of the size of microvascular obstruction (no-reflow area), if preseSuspected coronary artery disease can be most dramatically demonstrated during stress-induced ischemia on MR perfusion imaging performed during maximal coronary vasodilation. Vasodilatation can be induced by infusion of either dipyridamole or adenosine. Both agents act through stimulation of A2 receptors in the microvasculature. Adenosine is the direct agonist of this receptor. On the other hand, dipyridamole is a pro-drug, whose liver metabolite exerts its effect by an indirect mechanism on the endothelium – blocking the cellular reuptake of adenosine and inhibition of adenosine deaminase in endothelial cells, which leads to increased extracellular concentrations of adenosine. The stimulation of the A2 receptors relaxes the resistive arterioles, which normally autoregulate myocardial perfusion relative to coronary perfusion pressure. In normal non-ischemic myocardium, this results in maximal hyperemic vasodilation with an increase of myocardial perfusion without changes in myocardial blood volume . In myocTwo different protocols are currently used for the infusion of dipyridamole. The low-dose injection protocol consists of an infusion of a total dose of 0.56 mg/kg dipyridamole in 4 minutes, with imaging started immediately after completion of the 4 minute infusion. The high-dose injection protocol adds a second injection of 0.28 mg/kg dypyridamole for 2 minutes duration, commencing at 8 minutes after the beginning of the first injection. Thus, a total dose of 0.84 mg/kg dipyridamole is administrated in this high-dose dipyridamole infusion protocol. Imaging is initiated at the end of the second infusion, i.e., 10 minutes after the beginning of the first dipyridamole infusion. The advantage of the high-dose dipyridamole infusion protocol is a more intense, longer lasting and more predictive vasodilatation response than that obtained by the low-dose protocol.For the adenosine infusion protocol, adenosine is injected at a rate of 0.14 mg/kg/min, typically for 3–6 minutes for a total dose of 0.48 to 0.84 mg/kg, with imaging during the terminal portion of the adenosine infusion. Adenosine and contrast are administered via separate IVs to avoid large bolus drug delivery that increases risk of heart block. The adenosine infusion can be stopped when the contrast is completed. Both dipyridamole and adenosine can cause similar side effects, which may include light flushing, mild chest discomfort, and headache. Patients with significant coronary artery disease may experience angina pectoris. More serious side effects include atrioventricular (AV) conduction block, bronchospasm or cerebral hypoperfusion with potential neurological symptoms in the presence of significant carotid stenosis.The advantage of dipyridamole over adenosine is the lower cost and longer duration of vasodilation with a half-life of ~30 minutes versus < 10 seconds for adenosine, which gives a longer time period for performing the perfusion imaging. This longer half-life of dipyridamole can be associated with a longer duration of potential side effects that are not as self-limiting as adenosine. On the other hand, the short half-life of adenosine may give less time to respond to potential side effects. Because of the potential side effects, patients need to be monitored before, during, and after stress protocols, and equipment and qualified personnel for life support and resuscitation needs to be available. Since the vasodilating effects of both dipyridamole and adenosine can be abolished by ingestion of xanthine inhibitors, patients should withhold caffeinated beverages and theophylline for 24 hours prior to imaging . Dipyridevery heart beat.After induction of vasodilation by either adenosine or dipyridamole, first-pass perfusion imaging is performed during intravenous bolus injection of a gadolinium-based contrast agent. The objective of the test is the detection of perfusion defects in the ischemic area. Due to the extravascular distribution of most clinically approved contrast agents, such perfusion defects persist very briefly after bolus injection, before disappearing due to redistribution into the extravascular space. Hence, stress MR perfusion imaging requires very rapid image acquisitions. The focus of the pulse sequence will thus be maximal temporal resolution, at the cost of left ventricular coverage and spatial resolution. The best available perfusion sequences typically allow 3–4 short and/or long-axis slices to be acquired in a dynamic mode with a temporal repetition rate of Typical MR stress perfusion protocols are illustrated in Figure Patient safety during myocardial perfusion assessment requires appropriate staffing and technical considerations. The three types of staff typically involved in performing a stress CMR examination include technologist, nurse, and physician. The nurse and physician should be certified in basic and advanced cardiac life support with experience in anticipating, recognizing, and managing cardiac events that may occur secondary to or independently of pharmaceutical-induced effects. This is facilitated by having MR-compatible monitoring equipment in the scanner room with an additional display outside the room if needed. The minimum monitoring needs include continuous electrocardiographic display and heart rate measurement as well as periodic blood pressure recording. Capabilities for noninvasive oximetry are often helpful, particularly for the patient with obstructive lung disease of uncertain severity undergoing stress with vasodilators that may produce bronchoconstrictive effects. Weight-based vasodilator doses for stress are typically prepared by the pharmacy staff and delivered to the MR lab at the start of the procedure. In the MR lab area, there is also a point-of-care automated medication storage unit accessible by the clinical staff that is stocked with medications such as aminophylline, metoprolol, and lidocaine that may be needed for acute reversal or therapy of complications. In instances requiring defibrillation or resuscitation, there should be a plan in place that clearly delineates individual responsibilities when a patient needs to be brought out of the scanner room. One individual is typically responsible for patient transferal, another goes to get the resuscitation equipment or "crash cart", and the physician is responsible for directing appropriate inteventions. Such events may trigger the arrival of many individuals, who arrive to help with resuscitation but may not be facile with principles of MR safety. Thus, vigilance by the MR staff is required.Prior to the exam, the nurse typically screens the patient for clinical history that would preclude administration of adenosine or dipyridamole. This is done in conjunction with screening for MR contraindications, such as presence of ferromagnetic foreign body, aneurysm clip, intraorbital metal, or non-MR compatible implant. As noted earlier, a history of obstructive airway disease or conduction abnormalities should prompt the discussion of whether adenosine or dipyridamole stress testing is appropriate. A baseline electrocardiogram (ECG) is acquired prior to the MRI examination.After the exam, the patient is returned to the preparatory/recover area outside the scanner room where the nurse repeats a 12-lead ECG. The yield of this tracing is fairly low, given the rarity of ST changes due to adenosine. However, ischemic ECG changes resulting from adenosine portend a high likelihood of significant obstructive coronary artery disease. A post-procedure blood pressure measurement should also be documented, particularly if there was any significant blood pressure deviation during the exam.Qualitative interpretation of perfusion CMR images remains the mainstay of clinical reporting in 2007. Furthermore, stress perfusion interpretation almost always requires concomitant acquisition and interpretation of LGE images. A step-wise algorithm that begins with review of LGE images, followed by stress and rest perfusion images works well for overall classification of presence or absence of epicardial coronary disease in most cases . After cIn analyzing first-pass contrast enhancement images for quantitative assessment of cardiac perfusion, we need to be able to position a region of interest (ROI) within the wall, in order to follow the dynamic changes in MRI signal intensity. While in principle this is straightforward, there are some relevant issues that may need to be considered. First, we need to position the ROI carefully, so as to avoid contaminating the wall signal with signal from the adjacent blood. Another potential problem with ROI positioning can arise if there are premature ventricular beats, leading to variability of the size of the ventricular cavity and thus the position of the wall. Also, since patients are often unable to hold their breath for the full duration of the sequence of dynamic enhancement images, interactively repositioning of the ROI on sequential images may be needed to track a consistent portion of the heart wall.One frequent method of segmentation is the 17-segment model proposed by the American Heart Association, corresponding to the typical blood flow distributions of the coronary arteries . The epiAs there is no absolute scale of image intensity in MR, and there are many potential sources of variability of the image intensity, an approach to standardize and reproducibly quantify dynamic intensity changes is needed. One approach is to acquire additional calibration images, whose intensities must also be measured. For example, acquiring a "proton density" image at the same location can be used both to provide an "absolute" intensity scale and to correct for shading due to the use of local surface coils ,60. A seIn any attempt at quantitative analysis of dynamic first-pass perfusion images, we need to be able to account for the effect of potential variations in the rate, amount, and timing of the delivery of the contrast agent in the blood  on the resulting enhancement of the heart wall. One way to estimate the arterial input function (AIF) is to position an ROI within the left ventricular cavity, while minimizing contamination due to volume averaging, and follow the sequential signal changes in the blood.There are many potential problems associated with the determination of contrast concentrations from serial MR intensity measurements. First, the relationship between contrast concentration and signal is nonlinear, and also depends in a nonlinear way on the imaging parameters, such as the time between the saturation pulse that produces the T1 weighting and the image data acquisition. This nonlinearity can be particularly problematic when the concentration of contrast agent is high, as during the peak enhancement phase, as the response of the signal intensity may be effectively saturated, leading to a tendency to underestimate the concentration. Regional variations in the RF excitation field (B1) and the main magnetic field of the MR system (B0) can produce a corresponding variation of the amount of residual magnetization left after the nominal saturation pulse, with a resulting uncertainty of the amount of the contrast agent-induced signal increase . FinallyAssuming that we can determine the time course of the contrast agent concentrations in the arterial blood and the myocardium, calculation of the corresponding perfusion blood flow and related parameters can then be done. A hypothetical instantaneous bolus input ("impulse") of contrast agent at the tissue arteriolar level would produce a corresponding transient increase in the tissue concentration that would depend on the blood flow into the tissue, and would last for at least the duration of the transit of the labeled blood through the tissue. The mean transit time (MTT) of an instantaneous bolus is given by the ratio of the fractional blood volume of the tissue and the flow. As conventional contrast agents can diffuse from the vascular space into the extravascular space , the observed transit will be longer than the nominal vascular MTT. Obviously, any delay or prolongation of the delivery of the contrast agent to the tissue will be directly reflected in the observed tissue response, effectively being combined ("convolved") with the ideal impulse response, and will also need to be accounted for.A variety of approaches have been proposed to approximately correct the observed tissue enhancement for the effects of the AIF. These include calculating various parameters of the observed tissue enhancement curves, such as the time of arrival of the contrast agent, the time of the peak enhancement, and the slope of the enhancement curve, and correcting them by subtracting or scaling by the corresponding AIF parameters. The presence of noise in the data and other experimental limitations can lead to problems in reliably defining these parameters in practice. Furthermore, these empirical estimates don't allow a full calculation of the tissue transit effects or extravascular exchange of the contrast agent. A potentially better approach is to approximately mathematically undo ("deconvolve") the effects of the AIF from the observed tissue response, in order to estimate the corresponding underlying MTT and calculate the blood flow; a variety of approaches have been proposed for carrying out such calculations ,62,63.In light of the numerous obstacles outlined above, no quantitative perfusion analysis technique has gained widespread clinical use at this time. However, in research endeavors and in some clinical settings, one may use a relative index of myocardial perfusion reserve ,57,64,65Cardiovascular MR perfusion imaging with rest and stress acquisitions also helps answer a variety of clinical questions in the subacute or chronic setting. For example, the patient with atypical chest pain in whom ischemic heart disease is suspected may undergo rest/stress CMR perfusion imaging with LGE to define the presence or absence of flow-limiting coronary artery disease as the cause of symptoms. This is particularly helpful if there is known coronary artery disease and prior infarction. The superiority of CMR to delineate infarct scar becomes critical in providing this information in addition to extent of ischemia . In patiDetection of microvascular obstruction can assist in the distinction of chronic from acute infarcts, since microvascular obstruction occurs exclusively in acute myocardial infarction and disappears progressively over time . The preThe results of nine studies of 618 patients, which reported diagnostic accuracy on per-patient basis for detection of coronary artery disease versus detection of invasive coronary angiography, are summarized in Table At present, two multicenter studies have examined the influence of contrast agent dose on diagnostic accuracy. ,79 Most A few studies have compared diagnostic accuracy of CMR versus other techniques for detection of coronary artery disease. Ishida et al. showed aIn a study of 135 patients, who presented to the emergency department with chest pain, but without acute myocardial infarction, Ingkanisorn et al. reportedPanting et al. employed79 evaluated the prognostic value of this technique in 533 patients with chest pain or dyspnea and suspected coronary artery disease in comparison to dobutamine stress MR. Over a median follow-up of 2.3 years, ischemia by perfusion CMR was found to be the single best predictor of cardiac death or nonfatal myocardial infarctions and was superior to ischemia on dobutamine stress CMR. Presence of a normal perfusion test was predictive of 99% chance of a 3 year event-free survival.Finally, perfusion CMR has also been shown to have predictive value in patients with coronary artery disease. Indeed, Jahnke et al.1, allows a brief, single CMR exam to provide comprehensive assessment for etiologies of cardiovascular signs and symptoms that might otherwise require multiple testing and, therefore, less cost-effective healthcare.It should be remembered that clinicians have choices among several modalities when deciding whether or not to refer individual patients for perfusion CMR examination, particularly stress perfusion imaging. The value added by LGE imaging comes from its proven reliability in delineating extent of infarcted myocardium as well The authors declare that they have no competing interests.Gibbs artifact. This cine shows signal intensity profile resulting in dark rim artifact caused by Gibbs ringing.Click here for fileLAD-territory ischemia with adenosine stress perfusion. This cine shows myocardial ischemia in the distribution of the left anterior descending coronary artery. Stress perfusion images in basal, mid and apical short axis planes as well as a horizontal long axis plane are shown across the top, and rest perfusion images in the same planes are shown across the bottom. Ischemia appears as dark regions (hypoperfusion) in the stress images.Click here for fileSubendocardial ischemia with adenosine stress perfusion. This cine shows diffuse subendocardial perfusion abnormality, most prominent along the lateral wall, with adenosine stress. Stress perfusion images in apical, mid and basal short axis planes are shown across the top and rest perfusion images in the same planes are shown across the bottom. Ischemia appears as dark regions (hypoperfusion) in the stress images.Click here for file


A 59-year-old woman with a history of lung sarcoidosis developed general edema and exertional dyspnea. An electrocardiogram showed first-degree atrioventricular block with complete right bundle branch block. Chest X-ray showed cardiomegaly. Echocardiography showed diffuse and severe hypokinesis of the left ventricle (LV) and biventricular enlargement with severe tricuspid regurgitation. Myocardial scintigraphy disclosed a perfusion defect at the ventricular septum and hypoperfusion at the posterior wall and the apex. On cardiac catheterization, pulmonary capillary wedge pressure, right ventricular, and right atrial pressures were elevated. Coronary angiograms were normal. Myocardial biopsy of the right ventricle histologically revealed epithelioid cell granuloma with infiltration of fibrous cells. The patient's symptom and LV function were improved with conventional medical therapy for heart failure. This is a rare case of cardiac sarcoidosis resulting in biventricular failure. Sarcoidosis is a granulomatous disease of unknown etiology that primarily affects the lung and infrequently myocardium. Myocardial sarcoidosis is known to cause cardiac arrhythmias, electrical conduction disturbance, and rarely congestive heart failure . In cardA 59-year-old woman was admitted to the hospital in January 2001 due to exertional dyspnea and general edema with a functional class III of New York Heart Association (NYHA), which started from October 2000. She had suffered lung sarcoidosis in 1987, when bilateral hilar lymphadenopathy was noted on chest X-ray. She received no medication due to absence of symptoms and organ dysfunctions.On physical examination, blood pressure was 142/90 mm Hg and pulse was regular with 120 bpm. Pretibial and facial edema was noted without swelling of superficial lymph nodes. Heart and respiratory sounds were normal. Chest X-ray showed cardiomegaly with a cardiothoracic ratio of 0.67 but normal lung field. Computed tomography of the chest and ultrasound of the abdomen disclosed enlarged lymph nodes at the mediastinum and the hepatic hilus, respectively. An electrocardiogram (ECG) showed sinus tachycardia and first-degree atrioventricular block with complete right-bundle-branch-block. A Holter ECG monitoring during 24 hours showed 1275 beats of ventricular extrasystole with Lown grade 4B and 21 beats of supraventricular extrasystole. Two-dimensional echocardiography showed enlarged biventricles; left ventricular (LV) and right ventricular (RV) end-diastolic dimension were 58 mm and 45 mm, respectively . Diffuseμg/mL and 500.9 pg/mL, respectively, while the concentration of angiotension-converting enzyme was normal. Right heart catheterization revealed elevations of pulmonary capillary wedge pressure (mean 30 mm Hg), pulmonary artery pressure , RV ventricular pressure , and right atrial pressure (mean 23 mm Hg). Coronary angiograms were normal but left ventriculography showed a diffuse reduction in LV motion, especially in the anteroseptal and apical wall motion. A His-bundle electrocardiogram showed prolonged AH (164 msec) and HV (60 msec) intervals.On laboratory data, complete blood count and C-reactive protein level were normal. Liver, renal, and thyroid functions were also normal. Serum concentrations of lysozyme and brain natriuretic peptide were increased to 12.9 99mTc-tetrofosmin showed a perfusion defect at the ventricular septum and hypoperfusion at the posterior wall and apex, whereas 67gallium scintigraphy showed no myocardial uptake. Myocardial biopsy of the RV septum histologically showed epithelioid cell granuloma with infiltration of fibrous cells into the area of lost myocytes (Myocardial scintigraphy using myocytes , which cGeneral edema disappeared with furosemide, spironolactone and losartan, while exertional dyspnea and cardiomegaly were sustained. Thus, beta-blocker therapy with carvedilol was started with pimobendan and the dose was step wisely increased to 10 mg/day. When the patient was discharged, exertional dyspnea disappeared and cardiac function was improved to NYHA class II. One year later, echocardiography showed an increment in LVEF to 34% and a shortening of LV end-diastolic dimension to 53 mm, but no change in RV dimension. Right-sided heart catheterization showed pressure reductions in mean pulmonary capillary wedge pressure to 15 mm Hg, RV end-diastolic pressure to 15 mm Hg, and mean right atrial pressure to 17 mm Hg. Three years later, her cardiac function was further improved to NYHA class I. Echocardiography showed further restored LVEF to 54% and LV end-diastolic dimension to 45 mm with moderate tricuspid regurgitation. Throughout the clinical course until then, corticosteroid therapy was not conducted.The prior history of lung sarcoidosis, the atrioventricular block and the localized myocardial perfusion defect and histologically identified epithelioid cell granuloma have confirmed a diagnosis of cardiac sarcoidosis in this case. Clinical manifestations of cardiac sarcoidosis generally consist of cardiac arrhythmia, electrical conduction disturbance, and congestive heart failure, which occur in less than 5 percent of the patients with sarcoidosis –4. CongeWe initially considered that RV enlargement and dysfunction were secondary to LV dysfunction and tricuspid regurgitation. After the conventional medical therapy for heart failure, LV dimension and function were significantly improved, while RV dimension was unchanged despite the reduction in right-sided heart pressure. This suggested that RV enlargement and dysfunction were in part due to RV involvement by sarcoidosis.


Opening of an occluded infarct related artery reduces infarct size and improves survival in acute ST-elevation myocardial infarction (STEMI). In this study we performed tissue Doppler analysis ) and compared with visual assessment for the study of the correlation of measurements of global, regional and segmental function with final infarct size and transmurality. In addition, myocardial risk area was determined and a prediction sought for the development of infarct transmurality ≥50%.Twenty six patients with STEMI submitted for primary percutaneous coronary intervention (PCI) were examined with echocardiography on the catheterization table. Four to eight weeks later repeat echocardiography was performed for reassessment of function and magnetic resonance imaging for the determination of final infarct size and transmurality.On a global level, wall motion score index (WMSI), ejection fraction (EF), strain, and displacement all showed significant differences  between the two study visits, but MAM did not (p = 0.17). On all levels  and both pre- and post PCI, WMSI showed a higher correlation with scar transmurality compared to strain. We found that both strain and WMSI predicted the development of scar transmurality ≥50%, but strain added no significant information to that obtained with WMSI in a logistic regression analysis.In patients with acute STEMI, WMSI, EF, strain, and displacement showed significant changes between the pre- and post PCI exam. In a ROC-analysis, strain had 64% sensitivity at 80% specificity and WMSI around 90% sensitivity at 80% specificity for the detection of scar with transmurality ≥50% at follow-up. The treatment of acute myocardial infarction has undergone dramatic changes in the last decade. For ST-elevation myocardial infarction (STEMI), mechanical opening of the infarct related artery has gained widespread acceptance and the health care systems in many countries have adopted this policy for proper care of STEMI. Several studies have shown that short time to primary percutaneous coronary intervention (PCI) in patients with myocardial infarction reduces mortality -4, is asResearch has tried to elucidate the relative importance of various time delays ,9-11, diEcho wall motion analysis of myocardial ischemia is built on the concept that ischemia and scar confer a reduction in wall thickening and in longitudinal wall displacement and induce a delay in the onset of myocardial contraction. Various methods have been suggested for objective measurement of wall motion abnormalities ,14 and eLate gadolinium enhancement (LGE) MRI accurately determines infarct size  and has In this study, we performed echocardiography with tissue Doppler imaging simultaneously with primary PCI, on the catheterization table, to determine myocardial area at risk and to study whether wall motion score index (WMSI) and tissue Doppler parameters correlated globally, regionally and segmentally with the size of the final scar and its transmurality.Twenty-six patients (23 men) average age 65 ± 8 years (range 50 - 78), table Approval was obtained from the Regional ethical review board in Linköping. The study complied with the Declaration of Helsinki and with agreements on Good Clinical Practice. All patients gave written informed consent.At least three apical views were obtained with tissue Doppler (two-beat loops) while the patient was draped and prepared for acute PCI (GE V7 or GE V5 with 3 MHz transducers using harmonic imaging technology). At follow-up, a minimum of three apical loops were recorded, preferably in end expiration to minimize translational movement of the heart. The left ventricle was divided into 16 segments  . The myoTissue Doppler images were acquired with a frame-rate exceeding 90/s. Off-line analysis was performed using Echopac software . In each of the three apical views, six segments were defined and regions of interest (ROI) using sample volumes of 6 × 12 mm were applied. Tissue Doppler values in the apical anteroseptal and inferoseptal segments were averaged into an apical septal segment and in the anterolateral and inferolateral averaged into an apical lateral segment thus allowing conversion from 18 segments into a 16 segment model. After checking for aliasing in the velocity mode, myocardial strain and displacement curves were drawn and the peak values, regardless of delay time, were measured on two consecutive beats, if possible figure . Long axTo obtain global measurements of wall motion and strain, measurements from each segment were added and the sum divided by the total numbers of segments. To assess regional measurements of wall motion and strain in relation to infarct transmurality, numbers for the three segments of each wall  were averaged.The patients were placed in the magnet  in supine position. A circular polarized body-array surface coil was used in all measurements. ECG-triggered MR images were obtained during repeated breath-holds.Cine-MR imaging was performed with a balanced steady state free precession turbo field-echo (b-SSFP TFE) sequence that covered the entire left ventricle with on average 18 (range 10 - 23) short-axis slices and three long axis planes . Temporal resolution ranged between 26 - 41 ms (30 acquired phases). The inversion recovery turbo field echo (IR-TFE) sequence was a segmented 3D spoiled gradient echo sequence with TE = 1.3 ms, TR = 4.4 ms and TFE factor 43, leading to an acquisition phase time of 188 ms acquired during diastole. Slice thickness was 10 mm, intersection gap -5 mm (i.e. slices were overcontiguous), field-of-view 350 mm and image matrix 128 × 256. The contrast-enhanced images were acquired at the same slice positions as the cine-images, about 20 min after the administration of gadopentetate dimeglumine (Gd-DTPA) 0.2 mmol/kg bodyweight . Optimal contrast between hyperenhanced areas and normal myocardium was maintained by continually adjusting the inversion time to null the signal from the healthy myocardium.http://segment.heiberg.se, [Scar size was measured by two different observers on short-axis images using a freely available software "Segment" berg.se, . Infarct® Version 6.10 . The interaction between WMSI and strain on the detection of segments with a transmurality ≥50% was analysed with logistic regression.All heart-related parameters were reasonably well normally distributed and presented as mean ± (SD). The difference on global level between pre- and post PCI exams was analysed by two-sided t-test for paired observations. Spearman's rank correlation was used for global-, regional-, and segmental functional parameters vs. infarct size and infarct transmurality. The difference between normal segments  and segments with transmurality ≥ 50% on regional level was analyzed with Mann-Whitney's U-test. Receiver-operator-characteristics (ROC) curve analyses were performed using the statistical software MedCalcmethod) using the formula, first proposed by Dahlberg [method = √(∑di2/(2n)), where di is the difference between the i:th paired measurement and n is the number of differences. Smethod was also expressed as % over all means when applicable.Interobserver variability of the functional measures was expressed as standard error of a single determination . Two-tailed Left ventricular myocardial volume was 167.8 ± 36.9 ml (range 88 - 254 ml). Infarct size, determined at follow-up 4 - 8 weeks after PCI, was on average (± SD) 14.9 ± 5.6 ml (8.7 ± 7.4% of the volume of the left ventricular myocardium). Mean transmurality of affected segments was calculated for each of the 24 patients with follow-up scars ≥ 1%, giving a patient average of 44.3 ± 18.0% (range 8.5 - 76). At follow-up, WMSI improved from an average (± SD) of 1.6 ± 0.3 to 1.4 ± 0.3 .Corresponding numbers for ejection fraction were 38.5 ± 8.5% to 46.8 ± 8.5%  and for global strain -13.2 ± 3.3% to -15.7 ± 3.5% . Displacement changed from -5.4 ± 1.8 mm to -6.1 ± 1.4 mm . The change in MAM did not reach statistical significance .There were statistically significant correlations between infarct size and percent transmurality post-PCI (assessed by MRI) on the one hand and systolic ultrasonic measures pre and post PCI on the other table . The higWall motion score correlated moderately with transmurality in the acute phase and at follow-up  while the correlation for longitudinal strain vs. transmurality was lower at both time points  and for MAM still lower . In a comparison between walls with transmurality ≥ 50% and normal walls, WMSI, strain and MAM all displayed values that were significant. The change post-pre was not significant for any of the three measures, see table In the initial study, 390 out of 416 segments (94%) were successfully visualised and at follow up 410 of the 416 segments (99%). Wall motion score correlated moderately with transmurality in the acute phase and at follow-up  while longitudinal strain correlated weakly with transmurality at both time points . Displacement, regardless of the position of the segment  also correlated weakly with transmurality .The segmental values were analysed from two approaches. One was based on the evaluation of WMSI  and transmurality in regard to strain for segments that either deteriorated, improved or remained unchanged between the acute event and follow-up table . In the Initially, 231 out of 390 visible segments displayed wall motion abnormalities. 97 of these developed scar with transmurality > 1%, i.e. final scar affected 42% of the segments at risk table . Howevermethod) between three observers were for WMSI 0.50 (coefficient of variation (COV) = 32%) and 0.42 (COV = 30%) calculated for the pre- and post-PCI investigations. Corresponding methodological errors for the two observers of the MAM were 1.30 mm (12.4%) and 1.04 (9.3%), respectively. The methodological error in absolute numbers was for strain pre-PCI 5.4 and for post-PCI 4.5. Corresponding values for displacement were 1.59 and 1.43, respectively. COV for these measurements is of no interest since the values include zero. No significant differences were found, in regard to these measurements, between pre- and post PCI examinations. Smethod for scar assessed by MR post-PCI was 1.6 ml (11%) or related to myocardial volume 1.1% (12%).The calculated error  . Strain By averaging measurements from the three segment levels in each wall, regional measurements could be correlated with regional scar. This was done to allow a comparison of strain and wall motion scoring with the regional motion amplitude of the mitral annulus, which could easily be obtained from tissue Doppler velocities integrated over time ("tissue tracking"). We found a rather low correlation for regional MAM vs. transmurality, higher for regional strain and the highest for WMSI vs. transmurality.Evaluation of wall motion is very important in the clinical setting but draw-backs are the subjectivity  and the To determine myocardial salvage, an initial measure of myocardial area-at-risk is required. Myocardial oedema determined with MRI and myocardial perfusion determined with SPECT have been used, mainly because imaging can be delayed for several days for MRI and for 6-8 hours in regard to SPECT. In the present study, we selected wall motion assessment, either visual or by tissue Doppler, because of its low cost, availability at bedside, and the possibility to perform assessment in immediate relation to the intervention. We found that both methods identified segments that were to develop scar transmurality in excess of 50%. However, wall motion scoring performed better than strain measurement both in terms of detecting initially threatened segments and in avoiding false positive results. In total, 42% of threatened segments according to wall motion scoring developed significant myocardial scar. This result is in line with guidelines suggesting that the goal of acute infarct treatment is a final scar size < 40% of the initial risk area .The first echocardiographic examination was performed under difficult scanning conditions, while preparing the patient for acute PCI resulting in a compromised image quality. However, correlations were in the same range as for measurements performed at follow-up, when the imaging conditions were favourable. Strain measurements are known to be load dependent ,43, whicIn this study we have used a 16 segment model of the left ventricle in favour of the newer 17 segment model proposed by AHA . HoweverRegistration  is a major problem when studies are performed on patients at different time points and with different modalities. However, WMSI, strain, displacement and infarct transmurality were all assessed in the long axis view and care was taken to align the imaging plane with that used for measuring transmurality.Echocardiography, acutely performed while preparing patients for primary PCI, detected myocardial area at risk using two methods: subjective assessment of wall motion as well as objective measurement of deformation (strain). These measurements, repeated at follow-up 4-8 weeks later, correlated with the development of scar transmurality in excess of 50%, which is considered to be the limit for the return of useful wall motion post intervention. Analysis based on receiver-operator-characteristics curves showed WMSI to be superior to peak longitudinal strain in this prediction. Thus, advanced technological analysis of wall motion did not contribute additional value compared with a careful visual assessment by an experienced observer.The authors declare that they have no competing interests.LR performed a major part of all measurements and in writing the manuscript. PB participated in evaluating some of the patients and reviewed the manuscript. LB participated in the statistical analysis of the results and in writing of the manuscript. TT participated in planning the study, was responsible for the angiographic evaluation and reviewed the manuscript. JE planned the study, investigated some of the patients, performed measurements and analyses and took a major part in writing the manuscript. All authors have read and approved the final manuscript.This project was supported by Futurum - the academy for healthcare, Jönköping County Council, the Swedish Heart Lung Foundation, the Swedish Research Council, the Medical Research Council of Southeast Sweden, the Centre for Medical Image Science and Visualization, Linköping University Hospital, and the faculty of Linköping University.Gray scale 4-chamber view. Patient at follow-up, with thinning and akinesia in the distal part of the septum and in the apex.Click here for fileDoppler strain imaging 4-chamber view. The same patient as above. The blue trace displays low and delayed peak longitudinal strain (5%) from the apical septal segment while the yellow trace from the normal middle segment of the septum displays normal peak longitudinal strain at about 30%.Click here for fileTissue tracking 4-chamber view. The same patient as above. Tissue tracking of the mitral annular excursion is somewhat low at 8.5 mm in both the septal and the lateral wall. It is not reduced in the septum despite the apical myocardial infarct.Click here for file