To quantify myocardial injury in patients with acute ST-elevation myocardial infarcts (STEMI) by T1-mapping using Shortened Modified Look-Locker Inversion Recovery (ShMOLLI).Acute CMR imaging using late gadolinium (LGE) and T2-weighted imaging (T2W) is used to assess salvageable myocardium in STEMI patients post percutaneous coronary intervention (PCI) . However, current methods of assessing acute myocardial injury are being debated, and a more robust method would be desirable. T1-mapping quantitatively characterizes the myocardium without the need for comparing signal intensities against reference regions (ROI).Seventeen STEMI patients (age 55±8 years) underwent CMR imaging at 3T  12-48 hours post PCI. Forty-seven matching short axis slices were obtained for cine-SSFP, T2prep-SSFP, LGE, and T1-mapping (ShMOLLI). Segmentation was based on the AHA 17-segment model; volumetric fractions of injured myocardium per segment on LGE and T2W images were calculated using a signal intensity threshold 2SD above the mean intensity of a ROI in remote myocardium. Microvascular obstruction (MVO) identified on LGE images was manually segmented. For quantitative T1-mapping analyses, a threshold value of 1272ms (10% above control T1s of 1156±67 at 3T) was used. Wall motion was scored as normal, hypokinetic and akinetic. T1 values were calculated for segments with varying %LGE lesion and/or wall motion abnormalities (WMA) and for areas of MVO.2 =0.51) and by LGE and T1-maps (r2=0.48). A significant relationship was found between the volume of myocardial injury as assessed by T1-mapping, T2W and LGE, and the severity of WMA (p<0.01). (Fig.All patients had positive findings on cine, LGE, T2W and T1-mapping. The regions of myocardial injury assessed by the four modalities co-localized visually. Out of the 282 segments analysed, 39 were rejected for artifacts and 37 were identified as showing MVO and, hence were analysed separately. There was moderate correlation between the segmental damaged fraction assessed by LGE and T2W (rShMOLLI cardiac T1-mapping detects acutely injured myocardium in patients with STEMI and can identify segments with different degrees of damage as assessed by LGE.


The purpose of the study was to compare the accuracy and evaluation time of quantifying left ventricular (LV), left atrial (LA) volume and LV mass using short axis (SAX) and long axis (LAX) methods when using cardiovascular magnetic resonance (CMR).We studied 12 explanted canine hearts and 46 patients referred for CMR  in a clinical 1.5 T CMR system, using standard cine sequences. In standard short axis stacks of various slice thickness values in dogs and 8 mm slice thickness (gap 2 mm) in patients, we measured LV volumes using reference slices in a perpendicular, long axis orientation using certified software. Volumes and mass were also measured in six radial long axis (LAX) views.LV parameters were also assessed for intra- and inter-observer variability. In 24 patients, we also analyzed reproducibility and evaluation time of two very experienced (> 10 years of CMR reading) readers for SAX and LAX.2 = 0.98) and SAX (r2 = 0.88 to 0.98). LA volumes, however, were underestimated by 13% using the LAX views. In patients, there was a good correlation between all three assessed methods . In experienced clinical readers, left-ventricular volumes and ejection fraction as measured in LAX views showed a better inter-observer reproducibility and a 27% shorter evaluation time.In the explanted dog hearts, there was excellent agreement between ex vivo data and LV mass and volume data as measured by all methods for both, LAX (rWhen compared to an ex vivo standard, both, short axis and long axis techniques are highly accurate for the quantification of left ventricular volumes and mass. In clinical settings, however, the long axis approach may be more reproducible and more time-efficient. Therefore, the rotational long axis approach is a viable alternative for the clinical assessment of cardiac volumes, function and mass. Cardiovascular magnetic resonance imaging (CMR) is well recognized as a gold standard for functional imaging and assessment. CMR using state-of-the-art sequences has been shown to be very reproducible, is considered appropriate for many clinical indications  and therLong axis views (LAX) have been proposed as an alternative to SAX-derived methods . We aime®, Siemens Healthcare, Erlangen, Germany). All quantitative CMR parameters were assessed using certified software . All readers had training on drawing contours with special emphasis on how to avoid misinterpretation of the basal slice.All examinations were performed on a 1.5 T system  for an accurate representation of cavities, and then imaged with both radial LAX and SAX orientations for comparison. Three contiguous SAX stacks with full LA and LV coverage were analyzed separately  and six radial LAX slices were obtained as per published protocols [We assessed 46 individuals, . 4 were healthy volunteers without evidence for heart disease, while 42 patients were randomly selected from clinical referrals for functional imaging, tissue characterisation and/or viability. The study was approved by the local ethics committee and informed consent was obtained from each individual.Standard Steady-State-Free-Precession (SSFP) cine sequences were used for all approaches. Typical parameters were: TE 1.1 ms, TR 2.31 ms, FA 75°, matrix 340 × 284 mm, pixel size 1.3 mm × 1.4 mm and an IPAT factor 2. With 25 lines per segment, the effective repetition time typically was 57 ms. SAX acquisition was performed as multiple short axes across the entire LV in an imaging plane perpendicular to the LAX of the LV with a slice thickness of 8 mm and a 2 mm gap. The LAX slices were performed using 6 slices rotating in 30 degree increments around the anatomical LV LAX.42, Circle Cardiovascular Imaging Inc., Calgary, Canada) by well-trained observers. Endocardial and epicardial contours were drawn manually for the LV at end-systole and end-diastole in each data set.CMR image analysis was performed using certified software , end-systolic (ESV), stroke volume (SV), ejection fraction (EF), and LV mass were assessed by three independent observers. LV mass was measured at end-systole by both methods because of the easier definition of the endocardial borders in the contracted myocardium. The time needed to complete assessments was recorded in a randomly selected subgroup of 12 individuals.2). The mean difference between observations was calculated by averaging the absolute value of the difference between methods. Likewise, the difference for inter- and intra-observer variability was calculated as the absolute value of the difference divided by the initial measurement. Both absolute and relative differences between methods were calculated and Bland-Altman plots calculated . LA volumes were significantly correlated with SAX methods  table . There wSeventeen of the 42 patients referred for CMR did not reveal any abnormalities, while 25 had various cardiac conditions. Image quality was good in all cases, none of the patients were excluded from the analysis.There was a good correlation with no significant difference between SAX and LAX evaluation Table .Inter-observer variability was smaller with LAX measurements for LVEDV, LVESV and LV-EF Table . ResultsFor less experienced readers, the time of evaluation for SAX was 13 minutes and 8 seconds, while the time of evaluation for LAX was slightly less, 12 minutes and 42 seconds. Required evaluation times for experienced readers are shown in table Our data indicate that both, cross-referenced short axis and long axis views provide accurate measurements of volumetric LV parameters. This is not specific for CMR and has implications for other imaging techniques such as CT. Furthermore, our data indicate that long axis views take less time for evaluation. Another advantage of long axis views is the low susceptibility to errors induced by misinterpretation of slices close to the mitral valve. In fact, a post-hoc analysis of our data showed that errors of standard short axis data were due to inclusion or exclusion of the most basal slice, while there was no difference between cross-referenced and long axis results. Therefore, long axis planes may be a useful approach in most routine clinical situations.LV mass was larger when calculated by SAX. This could be due to the inclusion of trabeculations and papillary muscles in SAX while only papillary muscles were included in LAX; however, we were concerned that including both trabeculations and papillary muscles in the LAX would lead to an over-estimation in LV mass due to the use of rotational volumetry calculation . AnotherMost validation studies have been performed using SAX measurements of LV mass -10. FurtWe did not systematically assess the impact of ventricular shape criteria on our results. Although this has not been studied systematically, a highly irregular morphology may limit the accuracy of LAX data . In the When compared to an ex vivo standard, both, short axis and long axis techniques are highly accurate for the quantification of left ventricular volumes and mass. In patients, however, the long axis approach may be more reproducible and more time-efficient. For the analysis of left ventricular volumes by tomographic techniques, mass and function in hearts without severe shape alterations, a long axis approach may be a viable alternativeOliver Strohm is an advisor to Circle CV Imaging Inc., Calgary, Canada. and Matthias G. Friedrich is on the board of directors of Circle CV Imaging Inc., Calgary, Canada.LM, MM, MC, and JC were involved with the patient component of the study and assisted in drafting the manuscript. HC completed the ex-vivo component of the study and assisted in drafting the manuscript. JG was involved in both patient and ex-vivo scanning components.MF and OS designed and coordinated this study. All authors read and approved the final manuscript.


Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation, cirrhotic cardiomyopathy, and pulmonary vascular abnormalities. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include neurohumoral and vascular dysregulations. Accumulating evidence suggests that cirrhosis-related cardiovascular abnormalities play a major role in the pathogenesis of multiple life-threatening complications including hepatorenal syndrome, ascites, spontaneous bacterial peritonitis, gastroesophageal varices, and hepatopulmonary syndrome. Treatment targeting the circulatory dysfunction in these patients may improve the short-term prognosis while awaiting liver transplantation. Careful fluid management in the immediate post-transplant period is extremely important to avoid cardiac-related complications. Liver transplantation results in correction of portal hypertension and reversal of all the pathophysiological mechanisms that lead to the cardiovascular abnormalities, resulting in restoration of a normal circulation. The following is a review of the pathogenesis and clinical implications of the cardiovascular changes in cirrhosis. Patients with end-stage liver disease manifest a hyperdynamic circulation characterized by a decrease in the systemic vascular resistance and arterial pressure, and an increase in the heart rate and cardiac output. The clinical manifestations of hyperdynamic circulations include warm skin, spider angioma, palmer erythema, and bounding pulse. These cardiovascular changes were described over 50 years ago by Kowalski and Abelmann in a group of alcoholic cirrhotic patients. These fiDifferent pathophysiological mechanisms including neurogenic, humoral, and vascular dysregulations are implicated in the pathogenesis of these cardiovascular changes. The hyperdynamic circulation is most likely initiated by splanchnic and peripheral vasodilatation, leading to reduction in the effective arterial blood volume. This leads to a diminished renal blood flow in cirrhotic patients, which in turn stimulates the rennin-angiotensin-aldesterone system (RAAS), sympathetic nervous system, and antidiuretic hormone resulting in renal artery vasoconstriction, sodium retention, and volume expansion. WorseninThese circulatory changes lead to the development of multiple life-threatening complications including hepatorenal syndrome (HRS), ascites, spontaneous bacterial peritonitis (SBP), gastroesophageal varices, and hepatopulmonary syndrome.The following is a review of the pathogenesis and clinical implications of the cardiovascular changes in cirrhosis.Arterial vasodilatation is regulated by complex interactions of different vasodilator molecules. Cirrhosis leads to portal hypertension which induces portosystemic collaterals, allowing gut-derived humoral substances to directly enter the systemic circulation without detoxification by the liver. In recent years, nitric oxide (NO) has been recognized as the most important vasodilator molecule in the splanchnic and systemic circulation. NO is overproduced in cirrhosis; measured serum levels are significantly elevated in both cirrhotic patients and in animal models.–10 NO is1114et al demonstrated that the selective inhibition of iNOS causes peripheral vasoconstriction in patients with cirrhosis but not in healthy-matched controls, suggesting the contribution of NOS in the regulation of peripheral vascular tone and the hyperdynamic circulation of end stage liver disease.[Three isoforms of NO synthase (NOS) have been described: endothelial (eNOS), inducible (iNOS), and neuronal (nNOS). However, the leading isoform contributing to these vascular changes remains obscure. Multiple studies using nonspecific NOS inhibitors revealed that diminishing NO production resulted in normalization of the peripheral vascular vasodilatation. Ferguson disease. Other st disease.–19Other agents that are thought to play a role in the peripheral vasodilatation of cirrhosis include endocannabinoids. They areet al, demonstrated that primary afferent denervation by capsaicin, reversed the hyperdynamic circulation in cirrhotic rats. These findings suugest that primary afferent nerves may be the signaling pathway from the periphery to the CNS. Detection of a marker protein (Fos) in the brainstem and hypothalamic cardiovascular-regulatory nuclei of rats, immediately following portal vien ligation, indicates CNS activation. This is followed by hyperdynamic circulation, suggesting that the CNS activation plays a role in the pathogenesis of the hyperdynamic circulation. Additionally, blocking CNS Fos expression in cirrhotic rats resulted in eliminating the development of the hyperdynamic circulation.[More recently, multiple studies have shown a potentially important role of the central nervous system in the pathogenesis of the portal hypertension-induced hyperdynamic circulation.–25 Liu eIn addition to the hyperdynamic circulation, impaired ventricular contractility in response to stimuli was also described in cirrhotic patients.–27 Initi283In the absence of specific diagnostic criteria, the exact prevalence of cirrhotic cardiomyopathy remains unclear. The characteristic features of cirrhotic cardiomyopathy include (a) an attenuated systolic or diastolic response to stress stimuli, (b) structural or histological changes in cardiac chambers, (c) electrophysiological abnormalities, and (d) serum markers suggestive of cardiac stress.The impaired cardiovascular responsiveness in cirrhosis is likely related to a combination of factors that include cardiomyocyte plasma membrane physicochemical changes, attenuated stimulatory pathways, and enhanced activity of inhibitory systems which includes the following:et al. found that β-adrenoceptors signaling pathway is also impaired at different levels, starting with decreased membrane content and function of the stimulatory Gs-protein and ending up with impaired activity of the adenylate cyclase enzyme itself.[β -adrenergic receptor function: The role of β-adrenergic receptors was examined in multiple studies. Heart cell contractility is mainly determined by the stimulatory β-adrenergic receptor system. This syse itself.–34Muscarinic receptor activity: Muscarinic responsiveness was found to be blunted in cirrhotic hearts. MuscarinMembrane fluidity: Membrane fluidity is a term used to describe the degree of motional freedom for lipid moieties in the lipid bilayer of the plasma membrane. It has b34et al. have shown altered control of vascular tone by Ca++ and K+ channels. In their study, potassium channel blockers resulted in a significant increase in the vascular tone in cirrhotic rats compared to normal rats.[+ channels in ventricular myocytes from cirrhotic rats, which could potentially explain the prolongation of the QT interval.[Altered membrane fluidity also affects the function of membrane-bound ion channels. Moreau mal rats.38 Anotheinterval. AdditionNitric oxide: NO plays an important role in regulating the systemic and coronary vascular tone and its effect has been implicated in the pathogenesis of different cardiac dysfunctions including ischemic heart disease.41 Non-seet al. investigated its role in the pathogenesis of cirrhotic cardiomyopathy. They showed that HO-1 mRNA transcription and protein expression are significantly augmented in ventricles of cirrhotic animals compared to controls. They also showed that the hemeoxygenase inhibition significantly decreased the elevated cGMP content and reversed the decreased contractility of isolated BDL papillary muscles with no affect on control muscles.[Carbon monoxide (CO): CO is a known vasodilator that also exerts a negative effect on cardiac contractility through cGMP. CO stimu muscles. Based onet al. showed that the blunted contractile response of isolated left ventricular papillary muscle from cirrhotic rats is restored after preincubation with a CB1 antagonist.[Endocannabinoids: Upregulation of the cannabinoid signaling pathway has been described in chronic liver disease. Endogeno46tagonist.This circulatory dysfunction characterized by arterial vasodilatation and an increase in cardiac output is the proposed pathophysiological mechanism leading to sodium and water retention in patients with liver cirrhosis. Initiall50et al. revealed that octerotide and midodrine therapy significantly improved renal function and 30 day survival in patients with type 1 hepatorenal syndrome.[Several indicators of poor prognosis in liver cirrhosis are those which occur in association with extreme peripheral arterial vasodilatation, including a low mean arterial blood pressure, portal hypertension, and the elevation of different neuroendocrinal substances. Thus, treatment targeting the circulatory dysfunction in these patients may improve the short-term prognosis while awaiting liver transplantation.–57 A recsyndrome.P=0.035).[Transjugular intrahepatic portosystemic shunt (TIPS) insertion in cirrhotic patients leads to significant hemodynamic changes. TIPS causes a sudden increase in the preload in patients who are manifesting a hyperdynamic circulation at the time of the shunt insertion.–62 Multi60P=0.035). These fiP=0.035). These stThe consequences of cirrhosis-related cardiovascular alterations can also be manifested at the time of transplantation. During orthotopic liver transplantation (OLT), the hyperdynamic circulation is further compromised by the effect of anesthesia, mechanical ventilation, and surgical clamping. This results in significant reduction in the preload and subsequently a reduction in the cardiac output.67 RipollPostoperatively, inappropriate fluid management could lead to either hypovolemia or fluid overload, which can also be a strain on the heart. Metabolic derangements in the immediate postoperative period can also impair the cardiac contractility and hence result in significant swings in the systemic hemodynamic parameters.2.[Hemodynamic depression caused by hypocalcemia-induced citrate intoxication from massive transfusion was reversed after the administration of CaCl2. On the oet al. reviewed one hundred and ninety-seven patients to clarify the factors that may be able to predict cardiac complications following OLT, of whom 40% suffered one or more cardiac complications within 6 months of the surgery. Pulmonary edema was the most common complication occurring in 30% of patients; other complications included overt heart failure, arrhythmia, pulmonary hypertension, pericardial effusion, and cardiac thrombus formation. In this study, adverse intraoperative cardiovascular events, previous cardiac disease, and advanced liver disease as quantified by MELD score, predicted post-operative cardiac complications. Other variables including age, sex, OLT indication, body mass index, blood pressure and smoking, had a poor predictive value. Additionally, none of the pre-OLT investigations including chest X-ray, electrocardiogram, echocardiography, coronary angiopgraphy, pulmonary arterial pressure and 2-methoxy isobutyl isonitrile scan, predicted post-operative cardiac complications.[Cardiac complications following liver transplantation are common involving up to 70% of patients; fortunately most of these complications are subclinical. Pulmonar6766Intrapulmonary vascular abnormalities consisting of pulmonary vascular dilatation, intrapulmonary shunting and a low pulmonary vascular resistance, have been described in patients with liver cirrhosis78 This i818386et al. demonstrated in a CBDL model that not only does the macrophage production of of NO increase, but it also has an up-regulating effect on the CO production, contributing further to the pulmonary hemodynamic changes.[Endotoxin, TNF-α, endothelin-1 (ET-1), and CO are among other factors that may contribute to the pulmonary vascular changes. More rec changes. Circulat changes.89 Intrap changes.91Portopulmonary hypertension is another syndrome that has been associated with end-stage liver disease. Portopulmonary hypertension is less prevalent than hepatopulmonary syndrome, with an estimated prevalence of around 5%.93 The pa9498et al, following which multiple imaging studies using various molecules confirmed these findings.[The pulmonary vascular dilatation and the intrapulmonary shunts in patients with liver cirrhosis are the leading contributors to hypoxemia in advanced liver disease. The low pulmonary vascular resistance leads to a reduction in the intrapulmonary transit time. This leads to a decrease in the oxygen diffusion across the dilated pulmonary vessels, and has been labeled as the alveolar-capillary disequilibrium hypothesis. Based on101findings.–105 Despfindings.Liver transplantation is the only definitive treatment for hepatopulmonary syndrome with at least 85% of patients experiencing significant improvement or complete resolution of hypoxemia following surgery. However,et al. compared survival in patients with potopulmonary hypertension versus idiopathic pulmonary hypertension and showed that patients with portopulmonary hypertension have a higher risk of death when compared to patients with idiopathic pulmonary hypertension.[Portopulmonary hypertension is associated with high mortality, ranging between 50-90% in 5 years. Kawut rtension. Postoperrtension.113 Patiertension.et al. examined the hemodynamics of 12 patients at 2 weeks and 2 months following liver transplantation and suggested that most of the hemodynamic changes reverse.[et al. studied the cardiac output in 21 patients before and at 1 or 2 years following transplantation. They showed that the high cardiac output persist at both time periods.[Liver transplantation results in correction of portal hypertension and reversal of all the pathophysiological mechanisms that lead to hyperdynamic circulation. The effect of liver transplantation on the systemic hemodynamics has been studied by different groups. We studied the hemodynamic changes of 66 patients in the immediate postoperative period, comparing patients with viral and alcoholic cirrhosis. We found reverse. On the o reverse.119 Hende periods. Another


T2w-CMR is used widely to assess myocardial edema. Quantitative T1-mapping is also sensitive to changes in free water content. We hypothesized that T1-mapping would have a higher diagnostic performance in detecting acute edema than dark-blood and bright-blood T2w-CMR.We investigated 21 controls (55 ± 13 years) and 21 patients (61 ± 10 years) with Takotsubo cardiomyopathy or acute regional myocardial edema without infarction. CMR performed within 7 days included cine, T1-mapping using ShMOLLI, dark-blood T2-STIR, bright-blood ACUT2E and LGE imaging. We analyzed wall motion, myocardial T1 values and T2 signal intensity (SI) ratio relative to both skeletal muscle and remote myocardium.All patients had acute cardiac symptoms, increased Troponin I (0.15-36.80 ug/L) and acute wall motion abnormalities but no LGE. T1 was increased in patient segments with abnormal and normal wall motion compared to controls . T2 SI ratio using STIR and ACUT2E was also increased in patient segments with abnormal and normal wall motion compared to controls . Receiver operator characteristics analysis showed that T1-mapping had a significantly larger area-under-the-curve (AUC = 0.94) compared to T2-weighted methods, whether the reference ROI was skeletal muscle or remote myocardium . A T1 value of greater than 990 ms most optimally differentiated segments affected by edema from normal segments at 1.5 T, with a sensitivity and specificity of 92 %.Non-contrast T1-mapping using ShMOLLI is a novel method for objectively detecting myocardial edema with a high diagnostic performance. T1-mapping may serve as a complementary technique to T2-weighted imaging for assessing myocardial edema in ischemic and non-ischemic heart disease, such as quantifying area-at-risk and diagnosing myocarditis. T2-weighted cardiovascular magnetic resonance (T2w-CMR) is the standard imaging technique for detecting acute myocardial edema in vivo . It is uT2w-CMR techniques are sensitive to an increase in myocardial water content and/or free water fractions ,5-7. ConT1-mapping may provide a quantitative means to detect myocardial edema without the need for reference ROIs. Each tissue type exhibits a characteristic range of normal T1 relaxation times at a particular magnetic field strength . T1 and In this study, we compared T1-mapping using the novel ShMOLLI sequence , dark-blAll subjects gave written informed consent and ethical approval was granted for all study procedures.Consecutive patients demonstrating CMR features of acute Takotsubo cardiomyopathy or acute myocardial edema without infarction were prospectively enrolled. The diagnosis of Takotsubo cardiomyopathy was based on the proposed Mayo Clinic criteria : (1) an CMR studies were performed using a 1.5 T MR system . CMR scans assessed LV function, T1-mapping, edema and LGE, with matching short-axis images. T1-mapping was performed using the novel sequence ShMOLLI (Shortened Modified Look-Locker Inversion Recovery) ; dark-blo, matrix 192x192; ShMOLLI T1-maps are based on 5-7 images with specific TI = 100-5000 ms, collected using SSFP readouts in a single breath-hold, typically: TR/TE = 201.32/1.07 ms, flip angle = 35°, matrix = 192x144, 107 phase encoding steps, interpolated voxel size = 0.9x0.9x8mm, cardiac delay time TD = 500 ms; 206 ms acquisition time for single image; STIR [o, echo spacing 6.74 ms, TI = 170 ms, dark blood thickness 200 %, dark blood flip angle 180o, turbo factor 25, echo trains per slice = 7; ACUT2E TSE-SSFP: voxel size 1.9x1.5x8.0 mm, matrix = 165x256, TR/TE = 229.70/1.78 ms, effective TE = 98 ms, flip angle 180o, T2 prep duration = 24 ms, segments = 33, 5 shots per slice, bandwidth = 781 Hz/Px); phase-sensitive inversion recovery sequence: voxel size 2.0 x 1.5 x 8.0 mm, matrix 144x256, TR/TE = 800.20/3.36 ms, flip angle 25o).Typical imaging parameters for SSFP cine imaging were: voxel size 2.0x2.0x8.0 mm, TR/TE 39.6/1.12 ms, flip angle 55http://www.ittvis.com) to outline the endo- and epicardium, and then divided into 6 segments per slice using the anterior right ventricular-left ventricular insertion point as reference and for comparing segments amongst sequences.Matching short axis slices were compared across cine, ShMOLLI T1-mapping, STIR and ACUT2E imaging. Short axis images were manually contoured using an in-house software MC-ROI . Semi-quantitative assessment of wall motion abnormality was performed in MC-ROI. Segments were graded as: normal = 1, hypokinetic = 2, akinetic = 3, or dyskinetic = 4.After T1-maps were generated, the LV myocardium was contoured and segmented as described. The average T1 values were calculated as the average of the T1 values of all pixels for that slice or segment using the in-house software MC-ROI as previously described .2 maps; see Additional file 2 maps provide an additional means to identify artifacts and areas with potentially compromised T1 accuracy, which allowed critical assessment of the quality of T1-maps to increase the reliability of T1-mapping compared to some of the standard CMR modalities. Intra- and inter-observer variability of T1 measurements was assessed by two operators blinded to the clinical data; one slice of T1-map per subject was randomly pre-selected and analyzed for all subjects in the study.As T1-maps are derived from non-linear estimation based on a sequential series of SSFP images acquired after an inversion pulse , factorsmyo:remote = SImyocardium/SIremote myocardium and (2) T2 SImyo:skeletal = SImyocardium/SIskeletalmuscle, as previously published [Quantitative analysis was performed by comparing the LV myocardium in short axis against 2 reference regions of interest: (1) in remote myocardium, and (2) within adjacent skeletal muscle in the same slice, verified on a corresponding SSFP image. The T2 signal intensity (SI) ratio was calculated as: (1) T2 SIublished . Care waQuantitative analysis was performed the same way as for STIR images on coil intensity normalized and distortion corrected images. If no suitable reference skeletal muscle were available on a slice (i.e. affected by artifacts), then a ROI with a mean SI and SD similar to that of skeletal muscle of the nearest neighbouring slice is placed on the index slice.http://www.medcalc.org). Intra- and inter-observer reproducibility of T1 mapping measurements were assessed by using the Bland-Altman method [Results are presented as interindividual mean ± SD with differences considered significant when p is <0.05 as assessed by unpaired 2-tailed Student T-tests. Receiver operator characteristic (ROC) analysis was performed to identify cut-off values of T1 and T2-weighted methods for their ability to distinguish between normal and affected myocardial segments. Myocardial segments in patients were considered to be affected by edema if there were acute wall motion abnormalities  in this clinical population as defined above, while segments in controls with normal wall motion were considered unaffected. As patient segments with normal wall motion may or may not be affected by edema, these segments were not included in the ROC analyses in order to identify optimal cut-off values for the methods studied. Significance of ROC analyses was assessed using the method of Delong et al.  . CMR findings are summarized in Tables myo:skeletal by dark-blood and bright-blood T2w-CMR. There was good correlation between mean myocardial T1 values and T2 SI ratios using dark-blood and bright-blood T2w-CMR , T2 SI myo:skeletal by dark-blood T2w-CMR  but not with bright-blood T2w-CMR .Compared to controls, patients as a group had significantly higher mean myocardial T1 values, mean myocardial T2 SI From the 42 subjects, 205 matching slices (111 patient and 94 control slices) across cine, T1-mapping, dark-blood T2 and bright-blood T2 sequences were available  segments corresponding to the LVOT were rejected; on T1-maps, 142/1230 (11.5 %) segments were excluded due to off-resonance artifacts, poor T1 fit as evidenced by the RROC analysis Figure  showed tWe also performed ROC analyses based on patient groups to examine how T1-mapping performed against the T2 methods in detecting regional or global edema when different reference ROIs were used.In acute regional edema, where remote myocardium is more appropriate as a reference ROI for the T2-weighted methods, ROC analysis Figure A showed In Takotsubo cardiomyopathy where an entire myocardial slice may be diffusely edematous, skeletal muscle is a more appropriate reference ROI for the T2 methods, and ROC analysis Figure B showed Finally, to check for bias against any of the methods, when all 1230 segments (including segments affected by artifacts) were used, all of the original relative relationships were preserved, with T1-mapping maintaining a significantly larger AUC of 0.87 compared to the T2-weighted methods Figure . Relativr > 0.991) and agreement between T1 estimates obtained between both blinded operators. Bland Altman analysis of intra- and interobserver variability showed that the percentage difference in T1 values was ± 0.5 % (±5.6 ms) and the 95 % CI for the differences was ± 1.1 % of the average T1 (±11.1 ms). There were no statistically significant differences between intra- and interobserver variability.There was excellent correlation  should be for image analysis; it reports absolute T1 values, obviating the need for a reference ROI, and thus has an excellent performance in different models of edema, whether regional or global. Accordingly, T1-mapping can be useful in pathologies where edema maybe diffuse, patchy or not immediately obvious to the eye. Immediate visualization of the extent of injury may be facilitated by dedicated color schemes based on quantitative thresholds, an example of which is shown in Figure Unlike the T2w methods examined, ShMOLLI T1-mapping does not require 2 maps to ensure that the T1 fit is robust for all segments on the T1-map. The feature of R2 maps is described in detail with examples in the Additional file As our T1-mapping method is novel, we aimed to be as accurate as possible in setting the most optimal cut-off value for detecting edema and thus were stringent on selecting only the best segments  to include in the analysis. This was one of the reasons for the apparently higher rejection rate for T1-mapping compared to other modalities. T1-maps were assessed for quality and reliability in three ways: visual inspection of the T1-map itself, visual inspection of all seven of the raw T1 images for potential artifacts, and the use of RAs presented in the Results section, to check for bias against any of the methods tested, when we re-included all rejected segments affected by artifacts, it was reassuring to note that all of the original relative relationships on the ROC analysis were preserved, with T1-mapping maintaining its superior diagnostic performance with a significantly larger AUC of 0.87 compared to the T2-weighted methods Figure . RelativShMOLLI T1-mapping sometimes demonstrated typical SSFP susceptibilities to off-resonance artifacts and partial volumes effects, especially in very apical slices. These may be circumvented with frequency shifting and potentially by wide-band SSFP. As artifacts may cause falsely high or low T1 values, it is important to have methods for assessing the quality and robustness of T1-maps, such as those used in this study  CARDIAC GATED MAPPING OF T1. September 29, 2010.US patent pending 61/387,591: SKP and MDR. VMF: contributed substantially to the conception and design of the study, acquired and analyzed the data and drafted the manuscript; SKP contributed substantially to data analyses and critical revision of the manuscript; EDA contributed to data acquisition and critical revision of the manuscript; JMF contributed to data acquisition and critical revision of the manuscript; TDK, RPC, MGF, MDR have critically revised the manuscript; SN participated in the design and coordination of the study and critically revised the manuscript. All authors read and approved the final manuscript.Image Post-processing. Quality assessment of T1-maps – the use of R2 maps. Figure 6. Receiver operator characteristic curves according to patient groups for the detection of acute myocardial edema using all segments, including segments previously rejected for artifacts for all methods. (A) Patients with regional edema vs. controls. (B) Patients with Takotsubo cardiomyopathy vs. controls. AUC=area under the curve.Supplemental Material. Click here for file


Heart failure in children is a common cause of morbidity and mortality, with high socio-economic burden. Its pattern varies between countries but reports from Africa are few. The data are important to inform management and prevention strategies.To describe the pattern of congestive heart failure in a Kenyan paediatric population.This was a retrospective study done at Kenyatta National Hospital, Nairobi Kenya. Records of patients aged 12 years and younger admitted with a diagnosis of heart failure between January 2006 and December 2010 were examined for mode of diagnosis, age, gender, cause, treatment and outcome. Data were analysed using the Statistical Programme for Social Scientists version 16.0 for windows, and presented in tables, bar and pie charts.et al. (1992). Diagnosis was made based on symptoms and signs combined with echocardiography (echo) and electrocardiography (ECG) (38%); echo alone (12.7%); ECG, echo and chest X-ray (CXR) (11.4%); and ECG alone (10.8%). The underlying cause was established on the basis of symptoms, signs, blood tests, CXR, echo and ECG results. Common causes were infection (22.8%), anaemia (17.1%), rheumatic heart disease (14.6%), congenital heart disease (13.3%), cardiomyopathy (7.6%), tuberculosis and human immunodeficiency virus (6.9% each); 77.9% of patients recovered, 13.9% after successful surgery, and 7.6% died.One hundred and fifty-eight cases  patients’ records were analysed. The mean age was 4.7 years, with a peak at 1–3 years. The male:female ratio was 1.4:1. All the cases were in New York Heart Association (NYHA) class II–IV. Evaluation of infants was based on the classification proposed by Ross Congestive heart failure is not uncommon in the Kenyan paediatric population. It occurs mainly before five years of age, and affects boys more than girls. The majority are due to infection, anaemia, and rheumatic and congenital heart diseases. This differs from those in developed countries, where congenital heart disease and cardiomyopathy predominate. The majority of children usually recover. Prudent control of infection and correction of anaemia are recommended. Congestive heart failure in a paediatric population is a common cause of morbidity and mortality and is a serious public health concern, with tremendous socio-economic impact.This was a retrospective study at Kenyatta National Hospital (KNH), Nairobi, Kenya, which is a 1 800-bed capacity teaching and eastern African regional referral centre. It receives about 30 000 paediatric in-patients a year, mainly from black Kenyans of middle to lower socio-economic class. This hospital has four paediatric cardiologists and 40 paediatric cardiology beds. Ethical approval for the study was granted by KNH/University of Nairobi Ethics and Research committee.et al. (1992).Records of patients aged 12 years and younger who were admitted to the hospital with heart failure according to New York Heart Association (NYHA) classification II–IV between January 2006 and December 2010 were retrieved from the hospital registry. In infants, diagnosis and classification was based on criteria proposed by Ross Subsequently, the records were examined for cause and sub-cause of heart failure based on clinical, echo, ECG, CXR and laboratory findings. The causes were divided into six categories, namely congenital heart disease (CHD), rheumatic heart disease (RHD), anaemia, infections, cardiomyopathy, and other. In the categories where there were more than 25 patients, they were further subdivided according to specific cause. Those cases in whom some data on the parameters above were missing were excluded from the study.Data obtained were analysed using Statistical Programme for Social Scientists (SPSS) version 16.0 for windows, and presented in tables, bar and pie charts.One hundred and sixty-five cases were retrieved. Seven were excluded from the study: four in whom age, and three in whom the cause of heart disease was not recorded. One hundred and fifty-eight cases  were analysed.Diagnosis was made on the basis of symptoms and signs. In infants, these were feeding difficulties, increased fatiguability, tachynoea, intercostal retraction, dysponoea, grunting, tachycardia, gallop rhythm, cyanosis, rales and hepatomegaly. In older children, the symptoms and signs included exercise intolerance, somnolence, anorexia, tachypnoea, dyspnoea, orthopnoea, cough, wheezing, rales, gallop rhythm, oedema, hepatomegaly, and raised jugular venous pressure. The most common investigations used to complement clinical diagnosis were echocardiography combined with ECG (43.0%), and echo alone (12.6%). Echo, ECG and CXR were done in 11.4 %, and ECG alone in 10.8% Routine laboratory tests done for all patients included total blood count (TBC), peripheral blood film (PBF), and urea, electrolytes and creatinine (U/E/Cs) levels. Specific tests done were brain natriuretic peptide (BNP) (12.6%), C-reactive protein (CRP) (11.4%), tumour necrotic factor (TNF) alpha (11.4%), human immunodeficiency virus (HIV) ELISA (13.8%), CD4 counts (13.8%), and blood cultures (13.3%). The Mantoux test was done in those suspected to have tuberculosis.The mean age of these patients was 4.7 years, peaking at 1–3 years (range: 2 months – 12 years). The male:female ratio was 1.4:1, and the male predominance persisted through all age groups The most common single cause was infections (22.8%). Among these, the infections recorded were pneumonia (50%), upper airway (19.4%), throat (16.7%), and urinary tract (13.9%) infections. Anaemia (17.1%) was the second most common cause. The anaemia was due to malaria (48.2%), helminthiasis (22.2%), malnutrition (14.8%), and sickle cell disease (14.8%). Other causes included rheumatic (14.6%) and congenital (13.3%) heart disease, cardiomyopathy (7.6%), tuberculosis and HIV (6.9%) Eleven (7.0%) of the cases had multiple causes; six more than one, and five more than two. In six cases (3.8%), HIV was combined with tuberculosis. In five cases (3.2%), there were more than two causes: three in which bacterial infection was combined with cardiomyopathy and HIV, and two in which there was malaria, anaemia and infection.Treatment comprised appropriate correction of cause of heart failure, such as treatment of infection with antibiotics, blood on cause.11 Accordingly, age distribution is expected to vary between countries and centres.Observations of the current study reveal that heart failure constitutes about 1:1 000 of paediatric hospital admissions. It is difficult to compare rates among hospitals due to different hospital sizes, paediatric age limit, diagnostic criteria, age distribution and profile of causes.The modes of diagnosis combining clinical symptoms, signs and investigations are concordant with those practiced elsewhere.The mean age at presentation was 4.7 years, comparable to the 3.7 ± 3.5 years reported from Nigeria.The 1.4:1 male-to-female ratio recorded in the present study is comparable to the 1.5:1 for Nigeria,Infection was the leading cause of heart failure, followed by anaemia, and rheumatic and congenital heart diseases. This is at variance with literature reports from developed countries where most causes are congenital heart disease and cardiomyopathy.The infections most frequently associated with cardiac failure were pneumonia, upper respiratory and throat infections. This is concordant with reports from African countries where respiratory infection constitutes a significant cause of heart failure.14A remarkable observation of the present study was that HIV in isolation or combination was associated with heart failure in 12.7% of the patients. This is commensurate with other studies, which reported that heart diseases such as pericarditis, myocarditis, cardiomyopathy and endocarditis were associated with HIV infection.Tuberculosis in HIV-negative patients was associated with heart failure in 6.9% of cases. This appears in tandem with increasing reports of tuberculous pericarditis and myocarditis with no evidence of HIV, and disseminated TB.20Tuberculosis is a common problem in Kenya. Its association with congestive heart failure is important for two reasons. Firstly, patients with TB should be monitored for cardiac involvement. Secondly, in heart failure patients, TB should be considered an important differential diagnosis.Anaemia was the second most frequent cause of heart failure, affecting 17.1% of the children, again in sharp contrast with reports from developed countries (Table 2). This is, however, lower than the 28–46% reported from Nigeria.Rheumatic heart disease is highly prevalent in Kenya, causing 32% of adult heart failure.11Congenital heart disease is the most important cause of infant heart failure in developed countries.Cardiomyopathy is the major cause of heart failure among children with normal hearts in developed countries.26The treatment modalities provided in KNH are in tandem with conventional practice.Congestive heart failure is not uncommon in the Kenyan paediatric population. It occurs mainly before five years of age years and affects boys more than girls. The majority are due to infection, anaemia, and rheumatic and congenital heart diseases. This differs from those in developed countries, where congenital heart disease and cardiomyopathy predominate. The majority of children usually recover. Prudent control of infection and correction of anaemia are recommended.


Increased left ventricular (LV) stimulus intensity has been shown to improve conduction velocity and cardiac output. However, high-output pacing would shorten device battery life. Our prospective trial analyzed the clinical effects of high- versus low-output LV pacing.P<0.01; baseline versus Hi: 43.3 [35.5 to 51.1] versus 23.6 [16.1 to 31.1], P<0.01) and 6-minute walk distance . Although both Hi and Lo arms had some echocardiographic parameters that significantly improved compared to baseline , there were no significant differences observed when comparing the Hi- versus Lo-output arms.Thirty-nine patients undergoing initial cardiac resynchronization therapy device implantation with bipolar LV leads were assigned to 3 months of either high-output LV pacing (Hi) or low-output LV pacing (Lo) in a randomized, blinded crossover fashion. Hi and Lo settings were determined with a rigorous intraoperative protocol specific to each patient. Clinical and echocardiographic data were obtained at randomization, at 3 months, and a subsequent 3 months after crossover. Mean age was 66.4±9.8 years, and mean QRS duration was 159.3±23.1 ms. Compared to baseline, both arms had significant improvements in Minnesota Living With Heart Failure score  (baseline versus Lo: 43.3 [35.5 to 51.1] versus 21.3 [14.6 to 28.0], Low-output LV pacing with a relatively narrow safety margin above capture threshold affords significant improvement from baseline and is clinically equivalent to high-output LV pacing. These data support a strategy of minimizing the programmed LV safety margin to increase battery life in cardiac resynchronization therapy devices.http://www.clinicaltrials.gov. Unique identifier: NCT01060449URL:  Because epicardial pacing tends to have higher thresholds than endocardial pacing, and because those with higher thresholds have been shown to have greater variability in capture threshold over time,10 a relatively narrow margin between capture threshold and stimulus strength can result in occasional LV noncapture and inconsistent resynchronization.Despite the proven benefits of cardiac resynchronization therapy (CRT) with regard to risk of death and quality of life, approximately one third of appropriate CRT candidates fail to respond.11 Increased stimulus intensity expands the virtual electrode of directly excited myocardium beyond local regions of propagation block. Because it results in a larger region of LV myocardium being directly stimulated, it potentially would increase the chance of the most dyssynchronous LV regions being stimulated.13 Additionally, transient failure to capture the LV would be less likely with increased stimulus intensity. We and others have shown faster conduction times and evidence for expanded virtual electrodes in human ventricles when LV stimulus intensity is increased.16One simple yet unexplored way to partially overcome these obstacles is to increase LV pacing stimulus intensity.17 More frequent generator exchanges increase risks for patients.18 Therefore, the present study was designed to compare clinical measures of high (Hi) versus low (Lo) LV stimulus intensity in a double-blinded, prospective crossover in patients undergoing CRT implantation.Nevertheless, the potential benefits of increased LV stimulus intensity suggested by experimental data could be outweighed by the cost of reducing device battery life. Of all approved implantable cardiac devices, the average battery longevity in CRT devices is lowest, and predictions on battery longevity historically have been overestimated.2). The randomized crossover design of the trial was chosen to account for the effects of time on the measured variables, as well as intrapatient differences, given the modest size of the study population (The Stimulus Intensity in Left Ventricular Leads and Response to Cardiac Resynchronization Therapy (SILVeR-CRT) was a single-center, randomized, double-blind, crossover design trial conducted at Emory University Hospital and approved by the Emory University institutional review board. Informed consent was obtained from all patients before enrollment. A single LV lead model  was used in all study patients. The distance between the distal (tip) and proximal (ring) electrode of this lead is 21 mm, and the surface areas of both electrodes are identical  or the Lo setting (bipolar LV pacing or LV tip–to–right ventricular [RV] coil pacing) after implantation. All patients in the Hi group were programmed to LV bipolar pacing, thereby eliminating the potential for RV anodal capture. In those with LV tip–to–RV coil pacing in the Lo group, no cases of RV coil anodal capture were observed.During implantation, intracardiac electrograms during Lo and Hi bipolar LV pacing were obtained, and RV tip–to–ring sensing was obtained to measure acute intracardiac conduction times. The interventricular conduction times (IVCTs) at both Lo and Hi settings were measured between the intracardiac LV stimulus marker and the onset of the bipolar RV electrogram. ECGs were obtained during Hi and Lo LV-only pacing in most cases to analyze surface ECG changes in paced QRS morphology between Hi and Lo settings. Postoperatively, pacing was programmed off for baseline measurements.19 Echocardiographers and researchers involved in data collection were blinded to LV output assignment. Patients were continued on medical therapy as determined by their treating physicians.Baseline demographic data, 6-minute walk test results, Minnesota Living With Heart Failure (MLWHF) questionnaire responses, and transthoracic echocardiographic data were collected. Echocardiographic data included LV ejection fraction, LV end-diastolic volume, and LV end-systolic volume, as determined by Simpson's biplane method of discs. LV internal diameter in diastole and LV internal diameter in systole also were recorded. Finally, mitral regurgitation was quantified. Patients then were randomized by a third party not involved in data collection to the Hi-output arm or Lo-output arm. All patients underwent a single AV and VV optimization algorithm at enrollment with the use of previously published methods, which concentrated on maximizing the diastolic mitral inflow Doppler envelope for AV timing adjustments and maximizing aortic outflow envelopes for VV adjustments.At 3 months, 6-minute walk distance, MLWHF score, and echocardiographic data were collected again. The LV stimulus intensity was reprogrammed to the alternate pacing arm output, and the second 3-month follow-up period ensued. At 6 months (3 months after the crossover), clinical data measurements were repeated and the study was concluded for that patient . At the t test as appropriate. The distribution of all study variables had a reasonably normal distribution on Q-Q plot and histogram analysis. New York Heart Association class variables, MLWHF scores at follow-up, and end-diastolic diameter at low-output setting did meet significance (P<0.05) on Shapiro-Wilk test of normality. For these variables, additional analysis with nonparametric Wilcoxon matched paired tests showed similar results. All data are expressed as mean±standard deviation. P values and confidence intervals were 2 tailed, and a P value <0.05 was considered significant.The trial design resulted in paired data for each patient according to Hi or Lo LV settings. Statistical analysis was performed with SPSS . All the study endpoints were continuous variables and were analyzed with paired or independent-samples A total of 60 patients were screened during CRT implantation between July 2010 and December 2010. Of these, 9 patients were excluded because of screen failure , and 1 patient withdrew. Fifty patients provided written informed consent and were enrolled in the study. Of these, 6 patients were lost to follow-up, 3 patients had diaphragmatic stimulation during follow-up and exited the study, 1 patient exited because of pregnancy, and 1 patient died secondary to worsening heart failure. A total of 39 patients successfully completed the study and were included in final data analysis.The baseline demographic and clinical characteristics of the study group are provided in Of the 39 patients who completed the study, 22 (56.4%) initially were randomized to the Lo arm. At follow-up, 2 patients (both in the Lo arm) had partial loss of capture according to LV capture management monitoring. The thresholds were 0.175 and 0.5 V higher than programmed settings, respectively. These 2 patients were included in the analysis on the basis of intention to treat.P=NS).Transventricular conduction times and 12-lead ECGs for both arms were analyzed. Although there were striking examples of shortened conduction times and visible changes on QRS morphology in the same study participant between Hi and Lo arms , as a grP<0.01; Hi: 3.0±0 versus 2.4±0.6, P<0.001), 6-minute walk distance , and MLWHF  compared to baseline. End-diastolic diameter in the Lo arm and end-systolic diameter in the Hi arm also improved significantly as compared to baseline, and other echocardiographic parameters had nonsignificant trends toward improvement as compared to baseline in both trial arms.Results for the clinical and echocardiographic endpoints between baseline and the 2 study arms are shown in P>0.05) differences among groups, which supports that the sequence of randomization had no effect on the comparison of our experimental arms.In contrast to the improvements from baseline, comparisons of variables between the Hi and Lo arms showed no significant differences or observable trends in echocardiographic results, MLWHF score, New York Heart Association class, and 6-minute walk distance. In a separate analysis, the same comparisons were performed on the subgroup of study participants in whom a decrease in IVCT was observed with Hi LV pacing. Despite the observed shortening of IVCT, no improvement in clinical or echo parameters was seen in this subgroup. A final analysis to account for the effects of time and order of randomization was performed. Clinical and echocardiographic parameters of patients enrolled to Lo settings in the first 3 months were compared to those enrolled to Lo settings in the second 3 months. The same comparison was repeated for the Hi setting. This analysis showed no significant  and nonischemic patients (n=18). There was also no significant different difference in the 6-minute walk distance.P=0.013; Hi group: 15.3±14.9 versus 33.2±27.1, P=0.013). However, even at baseline, ischemic patients had significantly lower MLWHF scores .The ischemic patients had significantly lower MLWHF scores than those of nonischemic patients with both Hi and Lo pacing (Lo group: 13.8±14.0 versus 29.9±24.0, Finally, we considered the possibility that Hi pacing might affect only those who are “nonresponders” to CRT. Subset analysis of 10 patients who failed to respond echocardiographically to “Lo” LV pacing did not show significant improvement in any parameters when patients crossed over to the Hi arm.Our data suggest that, despite preclinical evidence that increased LV stimulus intensity improves conduction times and myocardial contractility, there were no clinical advantages to increasing LV pacing output in patients who have standard indications for CRT. These findings are important for several reasons.20 With our design, we were careful to choose a Hi setting that was sufficient for substantial expansion of the LV virtual electrode. The Hi setting produced simultaneous cathodal capture of the LV tip and anodal capture of the LV ring, which would alter the region of depolarization by a magnitude of ≍2 centimeters, based on the distance between the LV lead tip and ring electrodes.21 In almost all cases, this expansion occurred away from the apex of the LV, which has been shown to correlate with improved clinical response rates compared to more apical lead positions.22 Also, the change in depolarization between Hi and Lo settings was frequently apparent on a surface ECG during LV-only pacing, as seen in the example provided.First, our results indicate that expansion of directly stimulated myocardium on the order of centimeters is insufficient to improve clinical response to CRT implantation. There has been much interest in altering LV lead location to the region of greatest delay to enhance CRT response.We considered that this change in the virtual electrode might affect only those with clear evidence of improvement in transventricular conduction with the Hi setting. Therefore, a subanalysis of patients who showed improvement in IVCT with Hi settings was performed. This likewise showed no clinical improvements in follow-up. These findings suggest that if altering LV virtual electrode size or position alters CRT response, the alteration would have to be relatively large and would be difficult to achieve within a single venous branch.Second, our findings suggest that low programmed LV output to prolong battery life is feasible and that there is no additional clinical benefit of pacing at high output or of having a higher “safety margin” of LV lead capture. The monitored capture management algorithm also suggests that LV lead thresholds obtained on postoperative day 1 are relatively reliable and seem to be stable in the long term, inasmuch as only 2 of the 39 patients had capture loss detected at programmed settings of 1 V above LV tip threshold. These findings have valuable implications for the programming strategy of CRT devices and should aid in prolonging battery longevity.This crossover trial used paired data comparisons to increase power to detect changes, but there is a chance that the trial had insufficient power to detect small improvements in the clinical parameters provided. Nevertheless, the fact that we observed significant improvements from baseline for both groups suggests that clinically relevant differences were detectable in our population. The protocol-derived and blinded LV ejection fractions of the study group at enrollment were occasionally higher than those determined in the clinical setting used to guide decision for CRT referral. This allowed some patients who had protocol-derived LV ejection fractions >35% to be enrolled in the study. Despite continuous capture-monitoring algorithms used in the study period, there still could have been transient loss of capture that was not recognized. Finally, this trial assessed increased LV stimulus intensity in the CRT-eligible population as a whole, and the effect this intervention has on the prespecified subgroup of nonresponders remains to be explored.The results of this prospective crossover trial indicate that low programmed LV output is clinically equivalent to higher outputs and should be used to prolong battery life in patients undergoing CRT implantation.


Pulmonary Regurgitation (PR) accompanying with pulmonary artery dilatation is one of the most common complications after pulmonary valve stenosis repair during the late follow up period. PR is well tolerated first, but later it becomes the reason of the right ventricular dilatation and the morbid effects of it. Decision in the time of performing PVR is vitally important because severe PR ends up with RV volume overload and PVR is shown to be capable in reducing it and ameliorating the systolic activity afterwards. On the other hand PVR should have been performed as late as possible because of its limited time of life.A 57 year old man that underwent an operation of pulmonary comissurotomy for pulmonary stenosis and ASD closure 45 years ago admitted our clinic with the symptoms of congestive heart failure such as dyspnea, peripheral edema and oliguria. Hypertension, DM, hyperlipidemia, smoking and coronary artery disease were the other remarkable points of his medical past. He was hospitalised for a stent implantation of RCA in 2009 and because of atrial fibrillation due to congestive heart failure in 2011. Cardiac MRI findings were; severe PR, 48 mm PA, 101x76x60mm RV, 79x53x56mm LV and EF was 34.6%. Right and left ventriculography revealed that RVP and PAP were 35mmHg whereas PCWP was 24 mmHg. RCA had a lesion of 50% proximally and posterobasal akinesia in LV.PVR , Pulmonary Artery Aneurysmorrhaphy, CABGX1 and Tricuspid Kay Annuloplasty was performed. Aortic clamp time was 119, CPB time was 164 and the operation time was 330 minutes. Intubation period was 14, ICU stay was 46 hours, no (+) inotrope support was needed and he was discharged on the 6th day after.PVR and PA Aneurysmorrhaphy was performed successfully as a reintervention in this case for severe PR and PA dilatation, occurred in the late follow up period of pulmonary comissurotomy.


Coronary artery bypass graft surgery is a well-known and proven method of treatment for coronary artery disease. A modification of this method is complete revascularisation of the right ventricle by sequential bypass grafting of the right coronary artery, the effects of which on ventricular function need to be clarified. We sought to determine the effect of the sequential bypass graft method on right ventricular (RV) function utilising tissue Doppler echocardiography.A total of 35 coronary artery disease patients  were enrolled. Patients were examined pre-operatively with tissue Doppler echocardiography for RV function, and again postoperatively after the first month.p = 0.009 and 1.4 ± 0.2 vs 0.9 ± 0.2, p ≤ 0.01, respectively), while the A wave and isovolumic relaxation times  decreased. Although the S-wave peak amplitude decreased in group A patients, it did not reach statistical significance.Pre-operatively, there were no significant differences with regard to demographics or basal echocardiographic findings. On the other hand, postoperative right ventricular diastolic function was found to have improved significantly as the right ventricular E wave and E/A increased (9.5 ± 1.6 vs 7.6 ± 2.7 cm/s, Sequential, but not single, complete revascularisation of the right coronary artery appeared to improve the diastolic function of the right ventricle. Coronary artery bypass graft surgery (CABG) is a well-known and proven method for myocardial revascularisation. The technique used  may be of importance with regard to long-term patency of these conduits.The technical advantages of the sequential grafting method are the economical use of graft material and the decreased number of proximal anastomoses,In this study we aimed to determine the effects of complete revascularisation of the right coronary artery (RCA) via sequential venous bypass grafting on the RV diastolic function as determined by tissue Doppler echocardiography.n = 20) included patients who had sequential right coronary artery bypass and group B (n = 15) included the remainder who could not have sequential bypass due to anatomical or technical reasons. All patients had significant coronary artery disease (CAD) and were accepted for CABG within two months of the diagnostic coronary angiography. Transthoracic echocardiography was performed before the CABG operation.The study was approved by the local ethics committee and all subjects gave informed consent. Thirty-five (19 men and 16 women) consecutive patients undergoing CABG between 2006 and 2009 were enrolled into this prospective study. Group A  lesions were located proximally.Demographic data, including risk factors were recorded. Presence of hypertension was defined as systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg on two or more occasions, or use of an antihypertensive drug. Patients who were on antidiabetic medication  at the study entry or whose fasting blood glucose levels were higher than 125 mg/dl were considered to have diabetes mellitus. Hypercholesterolaemia was defined as total cholesterol level > 200 mg/dl or any medication being used. Patients were classified as cigarette smokers if they had smoked within the last 10 years. None of the patients had acute coronary syndrome.Exclusion criteria included a history of recent right-side myocardial infarction, left ventricle systolic dysfunction (ejection fraction < 50%), right ventricular ejection fraction < 40%, presence of atrial fibrillation, previous CABG, significant valvular heart disease, pulmonary hypertension (> 50 mmHg), significant pulmonary disease, or left bundle branch block on electrocardiogram.All echocardiographic measurements were performed by a single experienced investigator using an ultrasound imaging system  with a 2.5-MHz transducer equipped with pulsed-wave tissue Doppler. Heart rate during the examination was kept at 60 to 100 beats/min. Measurements were performed according to the recommendations of the American Society of Echocardiography.Pulmonary artery systolic pressure was calculated as the sum of the pressure gradient measured from the tricuspid regurgitation wave and estimated right atrial pressure.With the subjects in the lateral supine position, tissue Doppler recordings were obtained from the standard parasternal and apical views. Three major velocities were recorded at the annular sites: the peak major positive systolic velocity when the annulus moved towards the apex, and two major negative velocities when the annulus moved back towards the base (one during the early phase of diastole and the other during the late phase of diastole). The velocities were recorded online at a sweep speed of 50 mm/s. A mean of five consecutive cycles was used for the calculations of all echo-Doppler parameters. RV ejection fraction was determined using the ellipsoidal shell method. All measurements were performed one month after the operation.in situ LIMA was always the graft of choice for revascularisation of the LAD. The LIMA was harvested with a pedicle and preserved in a sponge with papaverine to avoid spasm. SVGs were used for revascularisation of the remaining coronary vessels. The pericardium was opened, followed by general heparinisation, and aortic and venous cannulation using a double-stage atrial cannula, after which cardiopulmonary bypass was initiated.All operations were performed by the same surgeon who had 10 years of experience of coronary artery surgery. Complete revascularisation was the ultimate goal in all patients. A median sternotomy was performed in all patients. The Cardiac arrest was maintained by warm blood cardioplegia under moderate hypothermia. A sequential venous graft was used for revascularisation of the RCA. The choice between individual and sequential technique was based on the anatomical position of the vessels and grafts. All coronary anastomoses were performed using a double-armed 7-0 polypropylene suture with a continuous suturing technique. Distal anastomosis was done end to side. Side-to-side anastomoses were performed in a diamond shape (graft axis perpendicular to coronary arteriotomy) and end-to side anastomoses parallel to the native coronary vessel axis The length of the graft and the distance between segments to be anastomosed were determined before the initiation of cross-clamping while the size of the right ventricle was optimal, as an ‘empty’ right ventricle would lead to erroneous selection of an over- or undersized graft. Proximal anastomoses were constructed on the ascending aorta with continuous double-armed 6-0 polypropylene sutures using a side clamp during rewarming. Complete revascularisation using the internal thoracic artery for left anterior descending lesions and saphenous vein grafts for other coronary arteries was the goal in all operations.t-test or Mann-Whitney U-test. A p-value < 0.05 was considered statistically significant in all comparisons.Statistical analysis was performed with SPSS software . Clinical data were expressed as mean values ± standard deviation and in percentages unless stated otherwise. Categorical variables were assessed using the Chi-square test. Continuous variables were compared using the unpaired Student’s p > 0.05). Maximum pulmonary systolic pressures did not differ between the two groups . There were no mortalities or complications noted in the postoperative period. RV ejection fractions before and after the operation were not different.The basal clinical and echocardiographic parameters for the patients is shown in p = 0.009 and 1.4 ± 0.2 vs 0.9 ± 0.2, p = 0.01, respectively), while RV mean A-wave peak amplitude and isovolumic relaxation times were found to be significantly decreased . Although the right ventricular S-wave peak amplitude decreased in group A, it did not reach statistical significance . These findings have suggested that RV diastolic function improved in the sequential CABG group of patients.Postoperative RV diastolic parameters are presented in Although the echocardiographic assessment of left ventricular function is simple and well established, there is no gold standard for assessing right ventricular function by standard echocardiography since the evaluation is complicated by the complex anatomy of the chamber. In general practice, physicians rely largely on non-invasive imaging methods for assessment of right ventricular function and two-dimensional echocardiography is still the mainstay for its analysis. Recently, alternative techniques have been proposed such as tissue Doppler imaging techniques, three-dimensional echocardiography, magnetic resonance imaging, and even invasive assessment of pressure–volume loops.12RV systole comprises a complex pattern of contractions of the RV myocardium along its long and short axes as well as rotation along its longitudinal axis. Despite these caveats, decreased RV function after CABG has clearly been demonstrated using the amplitude of tricuspid annular motion assessed by conventional M-mode or two-dimensional echocardiography immediately and six months after the operation.The findings of our study showed that RV diastolic function significantly improved in the patients who underwent saphenous bypass grafting of the RCA using the sequential technique, whereas the systolic function did not improve. To our knowledge, this issue has not been studied before. Decreased RV function is known to occur after CABG operation; both RV filling and RV contraction are impaired after CABG.While the E wave reflects RV relaxation in tissue Doppler examinations, the A wave is associated with atrial activity. The E/A ratio shows the passive elongatory ability of RV myocardial fibres, and a ratio < 1.0 refers to abnormal compliance.et al.On the other hand, the isovolumic relaxation time (IVRT) corresponds to the energy-dependent phase of the cardiac cycle. It was found to be significantly higher in the sequential graft group of patients, which may translate into improved compliance. These improvements may be due to haemodynamic advantages of sequential grafting of the RCA, as O’Neill It has been demonstrated that peak systolic velocity (S wave) < 11.5 cm/s identifies the presence of RV dysfunction with a sensitivity and specificity of 90 and 85%, respectively.This study has some important limitations. The sample size was relatively small. Only one site of the tricuspid annulus was studied. In clinical practice, recording of other tricuspid annular sites might not be feasible in all patients. In addition, no method was included to assess the global RV function. In fact, there is no consensus regarding the echocardiographic assessment of global RV function aside from the gold-standard MRI. Two-dimensional echocardiography using the ellipsoidal shell model for right ventricular volumetry provides usable results for clinical practice, and it has been reported that it yielded data on right ventricular function comparable to those from MRI.In general clinical practice, two-dimensional echocardiography can still be used to assess right ventricular dysfunction. Both systolic and diastolic RV functions are very important parameters in the peri- and postoperative period after CABG. Reducing right ventricular diastolic dysfunction via selecting the sequential, not individual, bypass technique for revascularisation of the RCA could help patients recover more rapidly and possibly improve their prognosis. Large-scale and randomised studies are still needed for assessment of the effect of this technique on long-term morbidity and survival.


P/dTmax and shifted the LV pressure–volume relationship curve to the left. These results show that activated RVLM astrocytes are capable of increasing sympathetic activity via release of ATP while facilitated breakdown of ATP in the RVLM attenuates the progression of LV remodelling and heart failure secondary to myocardial infarction.Heart failure may lead to hypoperfusion and hypooxygenation of tissues and this is often exacerbated by central and obstructive sleep apnoeas associated with recurrent episodes of systemic hypoxia which triggers release of ATP within the CNS circuits controlling sympathetic outflow. Using in vitro and in vivo models we tested two hypotheses: (1) activated brainstem astroglia release ATP and via release of ATP activate sympathoexcitatory neurones of the rostral ventrolateral medulla (RVLM); and (2) ATP actions in the RVLM contribute to sympathoexcitation, progression of left ventricular (LV) remodelling and development heart failure secondary to myocardial infarction. In vitro, optogenetic activation of RVLM astrocytes transduced to express light-sensitive channelrhodopsin-2 activated sympathoexcitatory RVLM neurones in ATP-dependent manner. In anaesthetised rats in vivo, similar optogenetic activation of RVLM astrocytes increased sympathetic renal nerve activity, arterial blood pressure and heart rate. To interfere with ATP-mediated signalling by promoting its extracellular breakdown, we developed a lentiviral vector to express an ectonucleotidase—transmembrane prostatic acid phosphatase (TMPAP) on the cellular membranes. In rats with myocardial infarction-induced heart failure, expression of TMPAP bilaterally in the RVLM led to lower plasma noradrenaline concentration, maintained left ventricular end diastolic pressure, attenuated decline in dThe online version of this article (doi:10.1007/s00395-012-0317-x) contains supplementary material, which is available to authorized users. Congestive heart failure is associated with an increased activity of the sympathetic nervous system. It is generally believed that increased sympathetic tone is maladaptive and detrimental, contributing to the progression of the disease , 26. ThePO2 and may contribute to the increases in sympathetic cardiac and vasomotor activities during systemic hypoxia  with release of ATP i transients evoked by mechanical stimulation of astrocytes expressing EGFP (control) and TMPAP were similar in amplitude, however, astrocytes transduced to express TMPAP displayed rapid [Ca2+]i recovery  to express a potent ectonucleotidase—transmembrane prostatic acid phosphatase (TMPAP) under the control of an elongation factor 1α (EF1α) promoter . To visue of ATP . Primary−1; i.m.)/medetomidine  anaesthesia. Data were sampled using a Power1401 interface and Spike2 software. Control measurements were taken 6–7 days after transmitter implantation for ~1 h every day for 2 weeks. Then, the animals were anaesthetised (ketamine/medetomidine) and a viral suspension containing LVV-EF1α-TMPAP–EGFP (1 × 1010 TU/ml) was microinjected bilaterally into the RVLM using stereotaxic coordinates indicated above. Therefore, the same animal served as its own control. The data acquisition began 7–10 days after LVV-EF1α-TMPAP–EGFP microinjections and continued for up to 7 subsequent days. Blood pressure and heart rate were sampled every first 10 min of every hour. Analysis was performed using a custom-made Spike2 script following previously reported protocols [Rats (250–300 g) were implanted with radio transmitters for chronic monitoring of the arterial blood pressure, as described earlier , 34. Brirotocols , 34.n = 50) were anaesthetised with a mixture of ketamine  and medetomidine , orotracheally intubated, and artificially ventilated with O2-enriched (30 %) air. A left thoracotomy was performed to expose the heart, the pericardium was opened and the heart was exteriorised. The left anterior descending coronary artery was ligated between the pulmonary outflow tract and the left atrium using a 5–0 Merisilk suture. Paleness of the anterior wall of the left ventricle (LV) confirmed successful coronary occlusion. Sham-operated rats were prepared in the same manner but did not undergo coronary ligation. The thoracic cavity was irrigated with 100–200 μl of a solution containing Penicillin  and Streptomycin  and the chest incision was closed. Anaesthesia was reversed with atipamezole (1 mg kg−1). Postoperative mortality within the 48 h after coronary occlusion was 35 % due to sudden cardiac death. Two days after MI or sham surgery, the rats were anaesthetised with a mixture of ketamine  and medetomidine  and LVV-EF1α-TMPAP–EGFP (1 × 1010 TU/ml) or LVV-EF1α-EGFP (1 × 1010 TU/ml), were microinjected bilaterally into the RVLM as described above.MI was induced using the coronary occlusion technique described in detail elsewhere , 35, 36.−1, i.p.), placed on a homeothermic blanket with body temperature kept at 37.0 ± 0.2 °C. The femoral artery and vein were cannulated and ECG electrodes were placed. To evaluate LV contractile function, LV pressure was recorded using a fibre optic pressure sensor  introduced into the LV chamber via the right carotid artery. Following a 30-min stabilisation period, the data were acquired using Power1401 interface, saved and analysed off-line using Spike2 software. The maximum rate of rise of LV pressure (LV dP/dTmax) was derived from the LV pressure recording using the slope function. Average waveforms (10-min data sets) were used to determine systolic blood pressure (SBP), diastolic blood pressure (DBP), LV systolic pressure (LVSP) and LV end diastolic pressure (LVEDP). At the end of the haemodynamic studies, the heart was arrested with KCl and removed. LV pressure–volume relationship curve was obtained using a double-lumen catheter as described in detail previously [Haemodynamic measurements were performed 6 weeks after MI or sham surgery. The animal was anaesthetised . Blood samples were gently mixed and immediately centrifuged at 5,000 rpm (20 min at 4 °C) followed by plasma collection and storage at −80 °C until assayed. Plasma noradrenaline concentration was determined by ELISA using a commercially available kit  according to manufacturer’s instructions.t test, or non-parametric Wilcoxon-Mann–Whitney U test, as appropriate. Data are presented as either mean ± SEM or median and interquartile ranges. Differences between the experimental groups with P < 0.05 were considered significant.The data were analysed by ANOVA followed by the Tukey–Kramer’s post hoc test, Student’s −1) , but was not affected by a P2Y1 receptor antagonist MRS2179  . This allowed patch clamp recordings from C1 neurones identified under green light and optogenetic stimulation of astrocytes using blue light, as previously described , 15. ActP < 0.01; Student’s t test), mean arterial blood pressure , and heart rate  -Katushka1.3 or ChR2-Venus (sympathetic and cardiovascular responses in both cases were similar and the data were pooled) resulted in a significant increases in renal SNA , although we could not test this in conscious rats with MI due to an unacceptable mortality rate.P = 0.3; Table P < 0.05; ANOVA/Tukey–Kramer’s test) and dP/dTmax , elevation in LVEDP   , attenuated decline in dP/dTmax  and shifted the LV pressure–volume curve to the left   . This hypothesis is supported by the evidence that cell-specific optogenetic stimulation of RVLM astrocytes activates presympathetic C1 neurones via an ATP-dependent mechanism.This study was motivated by the clinical evidence of sleep-disordered breathing in heart failure with 27 % of patients experiencing episodes of obstructive sleep apnoea and 38 %, central sleep apnoea . Both sy2+ [2+ waves using mechanisms similar to those described in our recent studies [1 receptor antagonist MRS2179 had no effect. In a similar experimental paradigm, MRS2179 was found to block activation of neurones in the nearby medullary retrotrapezoid nucleus [Astrocytes release ATP in response to various stimuli and previously were shown to respond to hypoxia with elevations in intracellular Ca2+ . It may  studies . Here, w nucleus  indicatiBased on the existing evidence, it might be expected that optogenetic activation of RVLM astrocytes in vivo would trigger an ATP-mediated signalling pathway to C1 neurones. Indeed, we found that optogenetic stimulation of RVLM astrocytes leads to increases in renal sympathetic nerve activity, arterial blood pressure and heart rate. These results, when considered together with the literature data reporting increases in the arterial blood pressure and sympathetic nerve activity in response to microinjections of ATP into the RVLM, suggest that upon activation brainstem astrocytes may release ATP which serves as an excitatory signal to the presympathetic circuitry.2+ excitation. Expression of TMPAP had a significant effect on Ca2+ responses in individual astrocytes and dramatically reduced the spread of Ca2+ excitation propagating among cultured astrocytes. Since Ca2+ ‘waves’ in astroglial cultures are known to be mediated via ATP release [In order to evaluate the role of this mechanism in sympathoexcitation associated with progression of heart failure, we developed a molecular strategy for facilitated breakdown of ATP in the RVLM based on a virally driven expression and insertion into the cellular membranes of a potent ATP-degrading enzyme TMPAP. This molecular tool was first validated in cell cultures using a model of mechanical stimulation-induced propagation of astroglial Ca release , TMPAP eWe next evaluated the effect of TMPAP expression in the RVLM on cardiovascular homeostasis in healthy freely behaving animals. It was found that arterial blood pressure and heart rate were not affected by TMPAP expression in the RVLM during either day or night phase of the circadian cycle.PO2 [It is possible that in healthy animals other mechanisms can compensate for the reduction in purinergic tone in the RVLM. However, this signalling pathway may become particularly important in the developing heart failure since ATP release in the medulla oblongata increases in conditions of low PO2 . A recenPO2 . It is pPO2 , and thiPO2 ). It is PO2 , 25 whicP/dTmax and shifted the LV pressure–volume relationship curve to the left. Decreased dP/dTmax at normal LVEDP in post-MI rats transduced to express TMPAP in the RVLM could be explained by a concomitant slight increase in LV volume leading to normalisation of the LVEDP, as evident from the analysis of pressure–volume relationship activation in heart failure is maladaptive and detrimental, contributing to the progression of the disease. We hypothesise that astrocytes are the main source of extracellular ATP capable of increasing excitability of the RVLM presympathetic circuits. By extension, procedures or treatments which suppress astroglial activation and/or interfere with ATP-mediated signalling in brain regions regulating cardio-respiratory homeostasis might be expected to have a significant beneficial effect on the failing heart.Supplementary material 1 (TIFF 216 kb)Below is the link to the electronic supplementary material.


We report the case of a 42-year-old patient with hypertrophic cardiomyopathy (HCM) who presented to the emergency department with severe shortness of breath one week following uneventful cesarean delivery. Thoracic CT ruled out pulmonary embolus and confirmed pulmonary edema. Asymmetric interventricular septal thickening was clearly identified, demonstrating that the heart may be evaluated even on a non-ECG gated study. Acute pulmonary edema in the postpartum period is an unusual clinical presentation of HCM. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inheritable condition. Only a few prior studies have reported regarding the course of pregnancy in women with HCM. A 42-year-old G4P1 with hypertrophic cardiomyopathy (HCM) presented to the emergency department seven days after uneventful cesarean delivery with severe shortness of breath. Physical exam revealed elevated jugular venous pressure, bilateral leg edema, and bibasilar lung crackles. Chest radiographs demonstrated bilateral pleural effusions and perihilar airspace opacities Figures . Thoracihttp://dx.doi.org/10.1155/2013/802352). Diastolic parameters were abnormal with an E/E′ of 19 mmHg indicating elevated left atrial pressure and a mild provocable left ventricular outflow tract gradient of 33 mmHg with amyl nitrate. Subsequent transthoracic echocardiography demonstrated normal systolic function  is an autosomal dominant inheritable condition with variable penetrance and natural history and is caused by mutations in one of nine genes encoding sarcomeric proteins . The incImaging features are variable given the phenotypic heterogeneity of patients with HCM. Asymmetric septal hypertrophy is the most common variant, accounting for 60–70% of cases . Other pThe differential diagnosis for myocardial hypertrophy includes restrictive etiologies such as amyloidosis and sarcoidosis, as well as the sequela of systemic arterial hypertension. In most cases of HCM, myocardial hypertrophy and thickening are asymmetric and there is an appropriate clinical and/or family history. Cardiac MRI is particularly useful in differentiating HCM from other causes of myocardial hypertrophy due to the ability of late gadolinium enhanced imaging (LGE) to characterize different patterns of enhancement .Heart disease is present in 0.5–1% of all pregnant women and is the most common cause of death among pregnant women in the developed world . CardiacOverall, the risk of a cardiovascular event during pregnancy in women with HCM who experience no or mild symptoms before pregnancy is low. However, careful monitoring is recommended particularly in the immediate peripartum period when large fluid shifts can lead to acute pulmonary edema as occurred in this case , 7. In tAnatomic and morphologic cardiac information may be gleaned even from a non-ECG gated thoracic CT performed for another indication. Acute pulmonary edema in the postpartum period is an unusual clinical presentation of hypertrophic cardiomyopathy.Supplementary Material: 42 year old female with hypertrophic cardiomyopathy and acute pulmonary edema. Transthoracic echocardiography  and short axis (Video B)), demonstrate asymmetric septal thickening in keeping with the diagnosis of hypertrophic cardiomyopathy, and normal systolic function. Diastolic parameters were abnormal with an E/E' of 19 mmHg indicating elevated left atrial pressure. There was no resting left ventricular outflow tract (LVOT) gradient. There was a mild provocable LVOT gradient to 33 mmHg with administration of amyl nitrate.Click here for additional data file.Click here for additional data file.