R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking–derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group . In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group . For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices ( Premature cardiovascular disease is the leading cause of death in patients with end-stage renal disease (ESRD). Excessive cardiac mortality is thought to be secondary to nonatherosclerotic processes, with sudden cardiac death being a predominant feature.Cardiac magnetic resonance (CMR) imaging is a useful tool in the detection of cardiac disease. One of the advantages of CMR imaging is tissue characterization.19Although increased myocardial native T1 times have been demonstrated in early CKD,In this study, we compared native myocardial global and septal T1 relaxation times as potential markers of diffuse myocardial fibrosis in incident HD patients with those of healthy volunteers (HVs). Ejection fraction is often preserved late into the development of cardiomyopathy.In the incident HD group, we examined the relationship between these variables and an emerging blood biomarker, galectin-3, which is potentially a surrogate of myocardial fibrosis.A total of 61 aged- and sex-matched subjects were enrolled: 28 HVs and 33 HD patients. Baseline demographic characteristics of the HD population and the prevalence of traditional cardiovascular risk factors in this group are shown in 2  versus the HV group (55.0 g/m2)  (P < 0.001). One participant in the HV group had LVH .P = 0.001).Left ventricular (LV) mass was significantly greater in the HD group: the median LV mass indexed to body surface area (LVMI) in the HD group was 69.8 g/mP = 0.056). LV end-diastolic volumes and end-systolic volumes were similar between the groups. Full cardiac parameters of both groups are detailed in LV ejection fraction was similar between the groups . Five paP = 0.025; septal T1 time in the HD group, 1184 ± 29 ms versus the HV group, 1163 ± 30 ms, P = 0.007 , for septal T1 with an LVMI = 0.449 (P = 0.009) (P = 0.003). Septal T1 times positively correlated with end-diastolic volumes: Pearson’s R for global T1 = 0.323, P = 0.067, for septal T1 = 0.380 (P = 0.029), for midseptal T1 = 0.462 (P = 0.007). T1 times did not relate to ejection fraction.In the HD group, LVMI correlated consistently with all measures of T1 times: Pearson’s = 0.009) , for midP = 0.008).Peak GLS was reduced in the HD group compared with the HV group  and negatively correlated with ejection fraction . In the HD group, GLS also correlated with increasing end-systolic volume , which is associated with a poorer prognosis in HD.In the HD group, GLS correlated with LVMI . LVMI did not correlate with hs-tropT or galectin-3. Septal T1 correlated with predialysis hs-tropT  but not with NT-proBNP or galectin-3. GLS showed a trend toward correlation with galectin-3 . There was no correlation between GLS and NT-proBNP or hs-tropT.In the HD group, LVMI correlated with NT-proBNP  and NT-proBNP . There were no demonstrated relationships between LVMI or strain and QTc.Twenty-eight (85%) HD participants had a pre-HD electrocardiogram available for analysis, and 27 of these subjects (96.4%) were in sinus rhythm. One participant had right bundle branch block. The median corrected QT interval was 435 ms. Significantly, there were interrelations of the Q-T interval time (QTc) with septal T1 . There was no correlation between T1 times and this postdialysis weight gain . Strain also was not related to this weight change. An average of participants’ HD ultrafiltration volumes for the 30 days before imaging correlated with LVM, but not LVMI (Spearman’s R = 0.422 P = 0.015). There was no relationship between any measure of T1 time and 30-day mean ultrafiltration . There was no correlation demonstrated between any measure of strain and ultrafiltration volumes.The weight difference between the “dry weight” at the end of dialysis the day before imaging and the weight at the time of scanning correlated with LVM (but not LVMI) . There was no correlation demonstrated between global, septal, or midseptal T1 times or strain and blood pressure. There was a negative correlation between dialysis urea reduction ratio and LVMI . Further supporting the implication that HD adequacy was strongly correlated with LVMI, there were correlations between adjusted calcium and phosphate values and LVMI .In the HD group LVM (but not LVMI) correlated with diastolic blood pressure, correlation of LVM with systolic BP did not reach statistical significance . T1 times and strain were not related to calcium or phosphate.T1 times did not relate to the urea reduction ratio. GLS negatively correlated with dialysis urea reduction ratios (Spearman’s 2 compared with 65.7 g/m2 in those with a hemoglobin ≥100 mg/dl (P = 0.008). Our study was not powered to detect a potential small difference in T1 times in anemic patients. Median global T1 time in patients with anemia was 1190 ms  versus 1171 ms  (P = 0.189). GLS was reduced in anemic patients: GLS: anemia = −13.5 ± 3.9% versus −18.6 ± 5.1% (P = 0.025).HD patients with anemia (defined as hemoglobin <100 mg/dl) had a higher LVMI than those without. The median LVMI in the 6 anemic HD patients was 92.1 g/mOf the HD participants, 81.8% were receiving dialysis through an arteriovenous fistula. There was no demonstrated difference in LVMI, strain, or T1 times across different types of dialysis access. No correlation was seen between age or dialysis vintage and LVMI, strain, or T1 time; 24.2% of participants were diabetic. There was no statistical difference in LVMI, any T1 measurements, or strain between those HD participants with and without diabetes.P < 0.001); for septal T1, it was 0.941 ; and for midseptal T1, it was 0.901 .Of a total 976 T1 regions of interest , 808 R = 0.885, P < 0.001). We analyzed midseptal T1 times alone on the assumption that the apical short-axis slice might be more susceptible to motion artifact than the midslice; however, midseptal T1 times were not of any greater value than septal T1 time. Furthermore, using only 2 segments to calculate midseptal T1 increases the risk of regional ischemia influencing results.Therefore, in order to ensure that we did not falsely assume that a localized high septal T1 time was representative of a diffuse process, we measured T1 times throughout 3 short-axis slices: basal, mid, and apical. Using the 16-segment model of the American Heart Association,Native T1 times are known to be locally higher in areas of cardiac injury, for example, after a chronic myocardial infarction.Interestingly, we saw a relationship between septal T1 and predialysis hs-tropT. Septal times also related to QTc. Increased corrected Q-T interval times are associated with an increased risk of sudden cardiac death.Our study showed no difference in ejection fraction between HV and HD groups. It is well-known that ejection fraction is often preserved until late in the development of cardiomyopathy, and thus it is not a reliable primary end point for renal clinical trials.23R = 0.344, P = 0.05). Given our small sample size, we consider this result to be of some interest. Galectin-3 is an established biomarker of myocardial fibrosis. The trend identified makes sense as GLS measured by speckle tracking echocardiography is predictive of histologic findings of uremic cardiomyopathy and cardiac fibrosis in rats with CKD.In this study, there was a trend toward a correlation of GLS with galectin-3  was less than that in many typical HD populations, and our study population was not racially diverse. We were unable to perform multivariable adjustments to assess for independence of any of our findings.Our study would have been strengthened by the addition of a control population of hypertensive patients with LVH and without renal disease. However, there is some evidence from other studies that included a control group that in contrast to LVMI, T1 times are independent of blood pressure.Without biopsy confirmation, we cannot be certain that the cardiac abnormalities identified in this population are representative of fibrosis. It is recognized that water content can prolong T1 times, and this is undoubtedly a limitation of our study as we cannot be sure of the precise influence of this on our results.T1 times are a potentially novel way to quantify cardiac tissue abnormalities in ESRD. In the future, they may be conclusively demonstrated to be a surrogate marker of fibrosis. Nephrologists should note that normal values will vary from scanner to scanner. The next steps for development of T1 mapping as a widely applicable clinical tool will involve each center developing robust normal values for each of their scanners. Phantom work will be required before any future multicenter collaborations run successfully.We showed that T1 times are abnormally high in the HD population. Perhaps in the future, change in T1 times could potentially be a primary outcome measure in renal clinical trials. However, a number of questions need to be answered before this can happen: what is the natural history of T1 times throughout the progression of CKD, do T1 times change after renal transplantation, how exactly are T1 times affected by fluid status variation, and are increased T1 times associated with increased risk of future cardiovascular events and mortality. To date, increased T1 times have been shown to be predictive of mortality in amyloidosisNCT01951404). A total of 28 age- and sex-matched healthy volunteers were recruited from a Glasgow-based study examining variations in native T1 relaxation times in healthy adults.Sixty-one participants were included in the study. All participants were older than 18 years of age and had no contraindications to CMR scanning. HD participants were eligible if they had commenced dialysis within the past 12 months; baseline scans for all eligible patients in 2 concurrent studies recruiting in Glasgow were used. In total, 33 HD patients were recruited from the Cardiac Uraemic fibrosis Detection in DiaLysis patiEnts study , and the ALTERED study .The HV group had no cardiovascular or systemic disease and had normal electrocardiograms. They were not treated for hypertension or hypercholesterolemia and were taking no regular medications. HD patients were excluded if they had atrial fibrillation (as this makes magnetic resonance imaging and electrocardiographic gating difficult). All HD patients had been receiving renal replacement therapy for less than 1 year. ALTERED patients were not taking allopurinol, had a life expectancy >1 year, and did not have echocardiogram-defined LV systolic dysfunction.All participants underwent 3-T CMR imaging  at the British Heart Foundation Clinical Research Centre, University of Glasgow. In the HD patients, CMR imaging was consistently performed on a postdialysis day. Baseline ALTERED study magnetic resonance imaging scans were used before any study intervention. A double radiofrequency coil array (anterior and posterior) was used. The scans were electrocardiographically gated. The imaging protocol included cine magnetic resonance with steady-state free precession and T1 mapping sequences.Basal, mid, and apical T1 maps were acquired in 3 short-axis slices using a motion-corrected, optimized, modified Look-Locker inversion recovery investigational prototype sequence without contrast administration . T1 imaging parameters included 267.84-ms repetition time, 35° flip angle, 1.06-ms echo time, 100-ms T1 of the first experiment, 80-ms T1 increment, 124 × 192 pixel matrix, 2.2 × 1.8 × 8.0-mm spatial resolution, 930-Hz/pixel bandwidth, and 17-heartbeat  scan time.A single observer analyzed anonymized images in a random order to determine cardiac indices including LVM and function by manually tracing endocardial and epicardial borders at end-systole and end-diastole on the short-axis cine images as according to well-established protocols.On the raw T1 images, LV contours were defined and copied onto the color-enhanced spatially coregistered maps. Using the anterior right ventricular-LV insertion post as a reference, T1 maps were segmented according to the American Heart Association 16-segment model.Each individual segment was assessed for the presence or absence of susceptibility and motion artifacts. After removal of any segments affected by artifact, a global T1 time was calculated from the mean of all remaining segments. A septal T1 time was calculated by averaging the acceptable anteroseptal, inferoseptal, and septal American Heart Association segments . Midseptal T1 time was derived from an average of included septal segments from the midshort-axis slice (segment numbers 8 and 9). T1 map reproducibility was assessed by blinded reanalysis of 25 randomly selected images by the same observer.n = 20).Dedicated feature-tracking software  was used on the horizontal long-axis cine acquisition. In a method previously described,In the HD group, predialysis 12-lead electrocardiograms were obtained for 28 participants. The underlying rhythm was recorded. Corrected QTc was noted from the electronic print out of each electrocardiogram.Frozen stored predialysis blood samples were obtained in the HD group for analysis of hs-tropT, NT-proBNP , and galectin-3 . All were analyzed using the manufacturer-recommended protocols and calibrations. Available collected blood tests from the time of imaging, including hemoglobin, urea reduction ratios, albumin, C-reactive protein, phosphate, parathyroid hormone, glucose, predialysis creatinine and potassium, lipid profile, as well as each HD participant’s medical and dialysis history including ultrafiltration volumes and postdialysis weights were obtained from electronic records.t tests (for parametric data) and Mann-Whitney U tests (for nonparametric data) were used to compare continuous indices between HVs and HD patients. Categorical data were assessed using the χ2 test or the Fisher exact test, as appropriate. Correlations within each group between continuous indices were assessed using Pearson’s and Spearman’s correlation coefficients for parametric and nonparametric data, respectively.All statistical analyses were performed using SPSS version 22  and STATA 13 . Paired At the time of the start of this study, there were few data to inform a power calculation using native T1 times at 3-T CMR imaging. Based on our normal volunteer study,The University of Glasgow holds a research agreement with Siemens Healthcare (UK). All the other authors declared no competing interests.


Previous MRI and US studies have shown the existence of functional and biochemical alterations in the myocardium after prolonged endurance exercise, demonstrating transient diastolic dysfunction . SimultaWe prospectively studied 50 runners enrolled on the 2014 « Tor des Géants » edition , without clinical evidence of personal history of cardiac or pulmonary disease. Subjects were studied before, at arrival, and after 3 days recovery. Imaging protocol included global and regional LV function analysis and quantitative MRI : T1, T2 and ADC values were obtained using respectively a MOLLI sequence, a radial multi-echo sequence, a Stejskal-Tanner diffusion sequence [27 finishers (54%) completed the longitudinal study.T2, T1 and ADC values significantly increased immediately after the race. ADC quickly normalized after recovery while T1, T2 markers remained higher than baseline (Figure It is the first study investigating the role of quantitative MR diffusion to explore human acute stress in humans together. ADC, T1 and T2 were all able to identify changes in subjects and related to several plasmatic biomarkers and therefore appear as valuable MR biomarkers of myocardial inflammation at least for this specific type of acute stress. Prior to a deeper understanding of the impact of ultra-endurance, this study hightlights an added value of ADC, that differ from T1 and T2 markers, to scrutinize acute stress phenomena in the myocardium. ADC represents a novel information, revealing more about water redistribution leading to ultraexercise-induced reversible myocardial inflammation. Overal it illustrates the usefulness and complementary nature of ADC as an emerging cardiac biomarker, foreseen to be deployed at short-term in the evaluation of innovative therapeutic strategies targeting inflammation.


Background: Exaggerated beat-to-beat variability of ventricular action potential duration (APD) is linked to arrhythmogenesis. Sympathetic stimulation has been shown to increase QT interval variability, but its effect on ventricular APD in humans has not been determined.Methods and Results: Eleven heart failure patients with implanted bi-ventricular pacing devices had activation–recovery intervals  recorded from LV epicardial electrodes under constant RV pacing. Sympathetic activity was increased using a standard autonomic challenge  and baroreceptor indices were applied to determine changes in sympathetic stimulation. Two Valsalvas were performed for each study and were repeated, both off and on bisoprolol. In addition sympathetic nerve activity (SNA) was measured from skin electrodes on the thorax using a novel validated method. Autonomic modulation significantly increased mean short-term variability in ARI; off bisoprolol mean STV increased from 3.73 ± 1.3 to 5.27 ± 1.04 ms (p = 0.01), on bisoprolol mean STV of ARI increased from 4.15 ± 1.14 to 4.62 ± 1 ms (p = 0.14). Adrenergic indices of the Valsalva demonstrated significantly reduced beta-adrenergic function when on bisoprolol . Corresponding increases in SNA from rest both off  and on  bisoprolol were also seen.Conclusions: Beat-to-beat variability of ventricular APD increases during brief periods of increased sympathetic activity in patients with heart failure. Bisoprolol reduces, but does not eliminate, these effects. This may be important in the genesis of ventricular arrhythmias in heart failure patients. Exaggerated beat-to-beat variability of repolarization (BVR) is strongly associated with pro-arrhythmia and is modulated by sympathetic activity . Informed consent was obtained in writing from all subjects.Studies were performed in 11 ambulatory heart failure patients  who were recipients of a CRT device . Patient characteristics are shown in Table Heart rate was fixed by constant right ventricular pacing using their implanted CRT device. The rate was chosen as the minimum rate required to maintain continuous capture at a fixed cycle length. A minimum adaptation period of 10 min took place prior to any recordings. The cycle length remained constant throughout the entire study and the same cycle length was chosen when studies were repeated on beta-blockade. The left ventricular epicardial lead was used to record unipolar electrograms, sampled at 512 Hz . The signals were digitized by the MP150 System using AcqKnowledge software  and sampled at 1 kHz.In addition sympathetic nerve activity (SNA) recordings were made using a novel method from a pair of bipolar skin electrodes in the Lead II position as in Doytchinova et al. . The sigRecordings were made with the subject seated upright. Physiological recordings were made simultaneously using multiple recording channels. Beta-adrenergic blocking agents (bisoprolol) were discontinued for 5 days prior to the study, which was sufficient wash-out time for all drugs in this population . Three patients could not be included as beta-blockers were not part of their regular medication.Each 30 s output from the CRT device was digitized and truncated to form one long data sequence of ~150 s in length. Any possible overlap between successive 30 s sequences was found by searching for matching traces at the start/end of successive traces and was removed. Raw, digitized electrogram (EGM) traces were then lowpass filtered at 80 Hz which removed high-frequency noise, but maintained the sharp activation gradients required to identify activation times. Figure ith) beat were then computed as.Activation times (ATs) were defined as the point of maximum negative downslope of the unipolar electrogram following the R-wave. Repolarization time (RT) was defined using the Wyatt method as the point of maximum upslope of the T-wave  of ARIs was computed, as previously defined . Here, SNAav values were computed over a 20 s window during the Valsalva and during a corresponding 20 s period of rest.Changes in SNA during sympathetic stimulation were quantified as in Doytchinova et al.  by comput-tests. Results were considered significant at P ≤ 0.05.For all subjects mean values of Systolic BP, SNA, and STV were averaged across both Valsalva maneuvers. Change following stimulus and comparison between off and on beta-blocker was assessed using two-tailed, paired, In the absence of beta-blockade mean baseline systolic blood pressure prior to the Valsalva was 129.6 ± 19.2 mmHg. Mean systolic blood pressures during each phase of the Valsalva were: Phase I = 152.3 ± 23.3 mmHg, Early Phase II = 92.7 ± 25.9 mmHg, Late Phase II = 97.5 ± 25.7 mmHg, Phase III = 65.9 ± 17.3 mmHg, Phase IV 142.8 ± 23.5 mmHg. Analysis of indices of sympathetic function demonstrated a mean overshoot in phase IV from baseline of 13.2 ± 11.1 mmHg and mean PRT of 5.26 ± 4.08 s.p < 0.01). Mean SNA increased from a resting value of 2.3 ± 1–3.7 ± 1.7 uV (p < 0.01). Individual blood pressure responses and changes in STV of ARI are presented in Table Without beta-blockade all 11 participants demonstrated an increase in mean STV of ARI following the Valsalva. Mean STV increased from 4 ± 1.22 ms at rest to 5.25 ± 0.9 ms (p = 0.05 and 0.04 respectively) . When repeated on established bisoprolol mean STV of ARI demonstrated a smaller magnitude of increase from 4.15 ± 1.14 ms at rest to 4.62 ± 1 ms (p = 0.14) following the Valsalva, which is also noted to be statistically non-significant. Figure p = 0.04). When repeated on bisoprolol mean rest SNA was 1.9 ± 0.8 uV and increased to 2.6 ± 0.8 uV (p = 0.05).A sub-group of eight participants additionally undertook repeated studies during established beta-blockade . Direct comparison of phases of the blood pressure response and indices of beta-adrenergic function are shown in Table p = 0.02). Although the observed increases in SNA were higher whilst off beta-blocker (2 ± 1.1 uV) compared to on bisoprolol (0.7 ± 0.4 uV) this was not statistically significant (p = 0.07). Figure Any relative reductions in the magnitude of the changes when on (compared to when off) beta-blockers were specifically analyzed by performing a direct pair-wise comparison of changes from rest during the Valsalva. Following the Valsalva a significantly greater increase in STV of ARI was seen when off beta-blockade (1.54 ± 1.29 ms) compared to when on bisoprolol (0.46 ± 0.78 ms) (Our study employed a novel methodology whereby ventricular APD was measured directly from the epicardium (as ARIs) in ambulatory patients with heart failure during an autonomic challenge induced by the Valsalva maneuver. The main findings were (1) The Valsalva was associated with an increase in BBV-APD; (2) The haemodynamic indices were consistent with increased sympathetic activity as is characteristic of the Valsalva; (3) The Valsalva increased SNA in skin recordings in keeping with a recent validation study .The Valsalva maneuver is an established method of increasing sympathetic activity whereby forced expiration impedes venous return resulting in a reduction in ventricular pressure and volume, and a baroreflex increase in sympathetic activity  beat-to-beat variability of ventricular action potential duration was increased during an autonomic challenge associated with increased sympathetic activity. These results accord with observations on ECG-QT variability. Our study on ventricular APD in ambulatory heart failure patients provides insight on mechanisms of known importance in the genesis of serious and fatal ventricular arrhythmias.BP, MB, JG, and PT conceived and designed the experiments. All authors took responsibility in collecting, analyzing and interpreting the data, with particular individual input in the following areas: electrophysiology (PT), analysis (MB), experimentation (BP). All authors contributed to drafting or revising the manuscript and all authors approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Heart failure is a common clinical syndrome caused by a variety of cardiac diseases. We report a rare case of familial transthyretin amyloidosis cardiomyopathy to heighten the awareness of this rare but lethal cause of heart failure, as therapeutic interventions such as liver or heart transplant could be curative in selected patients. Amyloidosis refers to the extracellular deposition of insoluble fibrils that are composed of low molecular weight subunits of a variety of serum proteins. The three most common types of amyloidosis that can affect the heart are light-chain (AL) amyloidosis, familial or senile transthyretin amyloidosis (ATTR) and secondary (AA) amyloidosis . TransthA 62-year-old Afro-Caribbean male was diagnosed with congestive heart failure with left ventricular ejection fraction (LVEF) 35% two years ago at his home country and presented with progressing shortness of breath, paroxysmal nocturnal dyspnea, orthopnea. Other comorbidities included well-controlled type two diabetes mellitus and hypothyroidism. His home medications included furosemide, metformin, and levothyroxine. He has two family members who passed away from unknown heart disease after their 50s. Vital signs were significant for chronic borderline hypotension. Examination showed elevated jugular venous pressure, decreased breath sounds at the left base, and S3 heart sound. The electrocardiogram (EKG) showed low QRS voltage, but no ischemic changes Figure .Troponins were equivocal. The N-terminal pro-B-type natriuretic peptide (NT-proBNP) was elevated. Chest X-ray showed a moderate left pleural effusion with basilar atelectasis and mild pulmonary edema. Transthoracic echocardiography (TTE) revealed global hypokinesis with LVEF 16% and severe concentric biventricular hypertrophy Figure .The patient was started on IV diuretics, dobutamine drip and had left-sided therapeutic thoracentesis with symptomatic improvement. Cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement revealed diffusely enlarged concentrically thickened ventricles with increased myocardial signal suggestive of amyloid deposition by appearance Figure .Left and right heart catheterization showed single-vessel coronary artery disases (CAD) isolated to the first obtuse marginal artery. Serum and urine immunofixations were negative. Right ventricular endomyocardial biopsy was obtained with amyloid subtype staining indicating ATTR Figures -5.Further genetic sequencing analysis showed pathogenic Val122Ile mutation and confirmed familial ATTR cardiomyopathy. The patient developed several runs of asymptomatic non-sustained ventricular tachycardia during the hospital stay. Due to high risk for deadly arrhythmias, the patient underwent single-chamber automatic implantable cardioverter-defibrillator (AICD) placement. He was started on warfarin for long-term anticoagulation due to nearly immobile atriums and ventricles. He was evaluated for heart and liver transplants. The liver transplant was postponed due to his heart condition, and ideally, should be pursued after the heart transplant in order to preserve the transplant heart from amyloid deposition. Due to severe hypertrophy with significantly decreased chamber size, left ventricular assisted device was not feasible. Eventually, he was deemed not to be a candidate for the heart transplant due to increased pulmonary vascular resistance. He is currently on palliative care.In patients without hypertension or valvular disease, biventricular hypertrophy on TTE should raise suspicion for infiltrative cardiomyopathy particularly when associated with low voltage on EKG, as hypertensive left ventricular hypertrophy or hypertrophic cardiomyopathy will usually have high/normal QRS voltage. The cardiac MRI with late gadolinium enhancement is very helpful in supporting the diagnosis of amyloid cardiomyopathy with a sensitivity of 80% and specificity of 94%, positive and negative predictive values of 92% and 85%, respectively . EndomyoWe presented a rare case of familial ATTR cardiomyopathy. Unfortunately, by the time of definitive diagnosis, the patient was no longer a candidate for heart or liver transplant, which are potentially curative interventions. Assessment of African American or Afro-Caribbean patients with unexplained heart failure should include a differential diagnosis of transthyretin amyloidosis, as early diagnosis is important to initiate appropriate therapeutic interventions.


Isolated ventricular noncompaction (IVNC) occurs because of interruption of trabecular morphogenesis in the myocardium leading to ventricular noncompaction. Patients present with heart failure or with systemic complications secondary to thromboembolism or arrhythmias. High index of suspicion is necessary for early diagnosis. We present a case of 48-year-old male with unexplained recurrent syncope who was eventually diagnosed with IVNC.  Cardiomyopathies have been classified based on morphological and functional phenotypes and each phenotype is further subdivided into genetic or nongenetic types. It is a rare disease that occurs due to the interruption of normal endomyocardial morphogenesis leading to noncompaction cardiomyopathy. It is almost always associated with other congenital anomalies like cyanotic heart disease or coronary artery anomalies. By contrast, isolated ventricular noncompaction (IVNC), is persistence embryonic isolated myocardial sinusoids in the nonexistence of other cardiac anomalies. Establishing correct diagnosis is pertinent for proper management and improving prognostic outcomes.A 48-year-old white male presented to our hospital with three-month history of shortness of breath and recurrent syncope episodes. He reported that his shortness of breath has been gradually progressive limiting his activity up to the level of walking short distances only. He denied history of hypertension or diabetes. Family history was significant for his sister in her fifties who died of heart disease. On examination, blood pressure was 118/87 mmHg, pulse was 96 beats/min, and respiratory rate was 18 breaths/min. On auscultation, there was normal S1, S2 with no gallops, or murmur noticed. Other physical examination was unremarkable. Chest X-ray was unremarkable as well. Electrocardiogram (EKG) showed sinus rhythm with premature ventricular complexes and nonspecific T wave changes . He repoFor further evaluation, echocardiogram was done that showed appearance of trabeculations and deep intertrabecular recesses , blood fTo further evaluate this cardiomyopathy, coronary catheterization was performed that revealed 50% stenosis of proximal left anterior descending, 50% stenosis of mid circumflex artery, and 50% stenosis of proximal right coronary artery which did not explain the aforementioned severely reduced cardiomyopathy. Patient was started on maximal medical management for treatment of his heart failure and was discharged on lifevest initially. He was then considered as a candidate of single chamber automated implantable cardioverter defibrillator (AICD) after repeating echocardiogram after 3 months with no improvement in ejection fraction. Following AICD implantation, he reported resolution of syncope on follow-up at 3- and 6-month interval.During embryology, human heart is the first organ to start functioning even before structural development is complete . Human hNoncompaction cardiomyopathy is more common in men as compared to women. The real prevalence is still unknown, but based on echocardiogram reports, its prevalence is 0.014% . Both faClinical features vary depending upon the severity of disease. The main clinical feature is heart failure and others include arrhythmias and thromboembolic events. Both systolic and diastolic heart failure can occur. In a cohort study of IVNC, systolic dysfunction is noticed in about 63% of cases . DiastolAppearance of prominent trabeculations and deep intertrabecular recesses principally in apical, mid-lateral, and mid-inferior regionDirect blood flow from the ventricular chamber into intertrabecular spaces, seen on color Doppler imagingAbsence of coexisting cardiac abnormalitiesThe maximal end systolic ratio of noncompacted layer of myocardium to compacted layer of myocardium above 2The end diastolic ratio of noncompacted layer of myocardium to compacted layer of myocardium above 2 in apical four chamber viewThe fact that systolic thickness of compacted layer of myocardium less than 8 mm may aid the differentiation of IVNC from normal heart as well as hypertrophic oneInitially, various echocardiographic diagnostic criteria . Cardiac MRI is helpful in diagnosing subendocardial perfusion defects, assessing the size as well as localization of noncompaction . AnotherThe treatment focuses on underlying symptoms and prevention of complications. Supportive care for both diastolic and systolic heart failure along with educating patient should be considered. Standardized treatments include the use of beta blockers, angiotensin converting enzyme inhibitors, and aspirin. Oral anticoagulation therapy is warranted in patients with history of atrial fibrillation and thromboembolism and those with ejection fraction of less than 40% . SymptomRecurrent syncope in patients with IVNC is a relatively rare presentation. We propose that IVNC should be considered in the differential diagnosis of unexplained recurrent syncope particularly in young patients. Also, AICD implantation is a feasible option for patients with heart failure or low ejection fraction or maybe with recurrent syncope.


Because of the increased bleeding risk, people with hemophilia (PwH) were advised to avoid physical activity (PA) until the 1970s . NeverthIn order to assess this question, 70 Turkish PwH with hemophilia A (84.3%) and B (15.7%) aged 19-61 years (mean: 38.0±11.8) were asked to complete a questionnaire that included questions on the sociodemographic characteristics and bleeding patterns of the patients, their attitudes towards exercise and sports, and their levels of involvement in PA.The study strikingly showed that Turkish PwH had a low level of awareness about PA. Less than one-fifth of the patients reported being sufficiently involved in PA. The level of involvement was highest (35%) in young adults (18-29 years) and lowest (0%) in patients aged 50-69 years (p<0.05). Conversely, in a German study , more thHowever, the present results might be associated with the severity of hemophiliac arthropathy, which is significantly more prevalent in older age groups (p<0.05).Despite the low awareness of PA, more than 40% of the patients met the current World Health Organization recommendations for PA , with yoOur results indicate that most of the patients avoid sportive activities (60%). Those who are physically active reported preferring moderate-intensity PA like walking or climbing stairs, instead of vigorous-intensity activities. As expected, the level of sportive activity significantly declined with increasing age (p<0.05).What are the reasons underlying the low level of PA in adult PwH in Turkey? Pain, fear of being injured, and lack of motivation were the most frequently reported reasons for avoiding PA. This is not surprising, given the late implementation of prophylaxis in Turkey (in 2005) and the resultant high prevalence of hemophilic arthropathy among elderly Turkish PwH causing pain and immobility.A multidisciplinary approach for implementation of suitable/safe physical exercises associated with less or no pain would help patients overcome the fear of being injured and thus increase their involvement in PA. The risk of injury can be minimized by following the recommendations for safe PA for hemophiliacs [6], which are often ignored, as shown by the patients .In conclusion, a reasonable treatment program for hemophilia should include much more than just factor replacement. PwH should be educated on the positive impact of PA on their physical, social, and psychological well-being. Furthermore, they should be well instructed about the recommendations for safe PA and what happens if they ignore the safety issues. PA should be considered as an integrated part of modern hemophilia treatment, which requires the collaboration of experts from various scientific fields.


Serial assessment of right ventricular ejection fraction (RVEF) predicts the clinical outcome of patients with pulmonary hypertension (PH). Cardiac magnetic resonance imaging (CMRI) enables RVEF monitoring, but its applicability is limited in clinical practice. This study aimed to examine the correlation between changes in CMRI-derived RVEF with those in echocardiographic indices in patients with precapillary PH.CMRI and echocardiographic indices of RV systolic function were evaluated at baseline and follow-up in 54 consecutive patients with precapillary PH , n = 23; non-PAH, n = 31). During follow-up, medical treatment was optimized according to the guidelines for PH. Using CMRI-derived RVEF as the gold standard, we examined the accuracy of five echocardiographic indices by correlation analysis and receiver operating characteristic (ROC) analysis and by calculating sensitivity, specificity, and positive and negative predictive values.After an average period of 9.5 months, CMRI-derived RVEF improved from 30.2% ± 10.6% at baseline to 41.4% ± 11.3% at follow-up. These changes significantly correlated with those in the five echocardiographic indices, i.e., %RV fractional shortening (r = 0.27), %RV area change (r = 0.46), tricuspid annular plane systolic excursion (TAPSE) (r = 0.84), RV myocardial performance index (RVMPI) (r = −0.72), and systolic lateral tricuspid annular motion velocity (TVlat) (r = 0.66). Of these indices, %RV area change, TAPSE, and TVlat significantly correlated with those of CMRI-derived RVEF in both PAH and non-PAH subgroups. ROC analysis showed that improvement in echocardiographic indices predicted a pre-specified improvement in CMRI-derived RVEF (>2.9%), with TAPSE and TVlat showing better accuracy over the other three indices.Echocardiographic indices modestly correlate with the changes in CMRI-derived RVEF in precapillary PH patients. Comparison among the five echocardiographic indices revealed that TAPSE and TVlat provide better accuracy than %RV fractional shortening, %RV area change, and RVMPI. In pulmonary hypertension (PH), chronic elevation of pulmonary arterial pressure (PAP) causes right ventricular (RV) dysfunction with its related symptoms and signs, as well as premature death.–3 TherefEchocardiography is a noninvasive and accessible modality suitable for repeated evaluation of RV morphology and function. Dedicated echocardiographic guidelines for RV assessment recommend the use of %RV area change, tricuspid annular plane systolic excursion (TAPSE), and/or Doppler parameters for evaluating RV systolic function. More recIn this retrospective study, we sought to examine the accuracy of echocardiographic indices for monitoring RV systolic function in medically treated patients with precapillary PH using CMRI-derived RVEF as a gold standard.We retrospectively analyzed consecutive patients with precapillary PH diagnosed by right heart catheterization (RHC) between April 2010 and February 2013. Inclusion criteria were mean PAP of ≥25 mmHg and pulmonary artery wedge pressure of ≤15 mmHg.[This study was approved by the ethics committee of the Hokkaido University Hospital, and written informed consent was obtained from all patients.Echocardiograms were obtained using Vivid q and Vivid S6  and images were analyzed offline after recording. Five echocardiographic parameters were obtained as previously reported;, 21–24 tity time. SystolicImage acquisition and analysis were performed by an experienced cardiologist (T.S.) who was blinded to the CMRI measurements.CMRI studies were performed on a 1.5-Tesla Philips Achieva MRI system  using master gradients (maximum gradient amplitude 33 mT/m and maximum slew rate 100 mT/m/ms), as reported in our previous study.[Offline image analysis of the RV was performed using commercially available software , according to the methods reported by Alfakih. Briefly,Within a week of being clinically stable, patients who met the inclusion criteria were assessed at baseline using World Health Organization (WHO) functional classification, plasma brain natriuretic peptide (BNP) concentration, echocardiography, and CMRI. During this period, all patients were hospitalized and were studied only when their PH-related symptoms  and vital signs  were stable.Patients with PAH were treated according to the goal-oriented strategy introduced in the PH guidelines published in 2009. The treaWe first analyzed the correlation between CMRI-derived RVEF and the five echocardiographic measurements at baseline and follow-up then examined the correlation between changes in both measurements.Receiver operating characteristic (ROC) analysis was performed to examine the ability of the echocardiographic indices to detect significant improvement in CMRI-derived RVEF. The cut-off level for significant improvement of CMRI-derived RVEF was determined as 2.9% based on the standard deviation (SD) of the interobserver variation reported by a previous study that used the same methodology of calculating RVEF.Using CMRI-derived RVEF as a gold standard, we calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the five echocardiographic indices of RV contraction. Similar to the ROC analysis, an increase of > 2.9% was used as the cut-off value for significant improvement in CMRI-derived RVEF. To obtain the cut-off values for the echocardiographic indices, we used our previously reported SDs of interobserver variations of each index, as folloCorrelation and ROC analyses and the calculations of sensitivity, specificity, PPV, and NPV were conducted in all precapillary PH patients and in the PAH and non-PAH subgroups, considering the possible differences in the demographics and the PH-related clinical data between the PAH and non-PAH subgroups.® Version 12  was used for statistical analyses and a p value of < 0.05 was considered statistically significant.JMPIn total, 82 Japanese patients were diagnosed with precapillary PH by RHC during the study period. Among these, 54 patients (66%) underwent baseline and follow-up RHC, CMRI, and echocardiography. %RV area changes at baseline and follow-up were not calculated in two patients  because of poor image quality, whereas the other four echocardiographic indices were evaluated in all 54 patientsThe baseline clinical characteristics of the 54 patients are shown in As shown in As shown in The changes in all five echocardiographic indices were significantly correlated with the changes in CMRI-derived RVEF . Among tThe ROC analysis  indicateThe present study demonstrated significant correlations between the changes in five echocardiographic parameters of RV systolic function and those in CMRI-derived RVEF in precapillary PH patients. Among the five echocardiographic indices, TAPSE exhibited the highest correlation coefficient (r) with the changes in CMRI-derived RVEF. The diagnostic performance of TAPSE and TVlat were higher than that of %RV fractional shortening, %RV area change, and RVMPI in the overall and subgroup analyses. The ability of the echocardiographic indices to identify improvements in CMRI-derived RVEF varied, with TAPSE and TVlat having the highest ability.Studies have shown a promising clinical role of serial assessment of RV function in PAH., 27, 28 Among the five echocardiographic parameters, TAPSE and TVlat appeared to provide better accuracy in monitoring of RV systolic function. Such superiority of TAPSE and TVlat has been reported in cross-sectional studies and the In a recent report by Spruijt et al., associations between changes in echocardiographic and CMRI indices were examined in 38 PH patients. Similar The clinical relevance of serial assessment of RV function has been less frequently reported for non-PAH PH patients than PAH patients. Recent studies, however, suggested there is clinical value in serial RV evaluation, particularly in CTEPH patients. Mauritz et al. and others have reported improved RV structure and/or performance in CTEPH patients after interventional procedures, such as pulmonary endarterectomy and balloon pulmonary angioplasty.–39 In adThe reproducibility of the echocardiographic indices should be discussed because the indices are likely to have substantial variation depending on the examiner and/or the condition of the patients. In this regard, we performed a Bland–Altman analysis, calculated the intraclass correlation coefficients, and reported the intraobserver and interobserver variabilities of the five echocardiographic indices in a previous study. In brieIn the correlation analysis of the changes in the CMRI and echocardiographic indices , the corThere were several limitations to this study. First, the present study included only a small number of patients with diverse etiologies of PH, which may have caused inconsistent results. For example, there was a significant association between ΔRVFS and ΔCMRI-RVEF in the overall analysis of the 54 participants, but the association did not reach statistical significance in the subgroup analysis of either the PAH (n = 23) or non-PAH group (n = 31). In addition, regarding the correlation between ΔRVFS and ΔCMRI-RVEF, the weak correlation between the two indices  may have also contributed to the lack of statistical significance in the subgroup analysis. Second, PAH and non-PAH groups were not matched in demographics and pulmonary hemodynamics. This, along with the limited reproducibility/variability of the echocardiographic indices, may have caused inconsistent results between the two groups, i.e., Δ%RV area change correlated with ΔCMRI-derived RVEF in the non-PAH subgroup, but it was not in the PAH subgroup. Third, this was a retrospective observational study with varying reasons and timing of follow-up. Fourth, although some of the PAH-approved drugs may have affected the myocardial function of the patients, the treaSerially measured echocardiographic indices of RV systolic function significantly correlated with CMRI-derived RVEF. In particular, the changes in TAPSE and TVlat are better correlated with those in CMRI-derived RVEF compared with %RV fractional shortening, %RV area change, and RVMPI in pharmacologically treated precapillary PH patients. The clinical relevance of serial echocardiographic evaluation of RV systolic function of PH patients needs to be further addressed in future adequately-powered prospective studies.


Gestational disruptions are linked to the risk of schizophrenia; but in most cases, there is a lack of a clear history or observable anomaly indicating that the disruptions are likely to be subtle . The time-locked development of cortical sulci in a human embryo is highly sensitive to developmental disruptions . We can retrospectively infer the likely timing of embryonic/fetal disruption in schizophrenia by studying the structure of major cortical sulci that represent lobar development in adults with schizophrenia.http://brainvisa.info/). Following the construction of 3-dimensional models of cortical folds, various sulci were automatically classified using a probabilistic algorithm with maximum depth computed for each identified sulcus. The 5 sulci were consistently labeled automatically across all subjects. The identified sulci were visually inspected to ensure that the boundaries are in accordance with Ono’s Atlas of Cerebral Sulci .Anatomical T1 MRI scans from a publicly available dataset (COBRE) of 68 patients with schizophrenia and 72 controls were used to evaluate the sulcal depth. 5 major primary sulci that are invariable, representing lobar development  with formation representing distinct developmental periods ) were chosen. Sulcal depth was measured using Morphologist interface of BrainVISA 4.5 . Gender  and age  also had significant effect in the model. Parameter estimates revealed a significant effect of diagnosis (Controls>Patients) for left superior temporal , right superior temporal , right inferior frontal  and left calcarine  sulci. 5 non-collinear factors representing the 5 bilateral sulci were obtained using varimax rotation, and related to overall MATRICS standardized composite score in patients using multiple regression. The depth of the superior frontal sulcus was the only predictor of the variation in the cognitive score .The above findings suggest that the gestational cortical disruption underlying schizophrenia is likely to predate, if not, coincide with the appearance of calcarine sulcus  and affects frontal, temporal and occipital lobes. Nevertheless, the burden of cognitive deficits may relate specifically to aberrant superior frontal development occurring in late second trimester.


Diastolic dysfunction is a major cause of morbidity in obese individuals. We aimed to assess the ability of magnetic resonance imaging (MRI) derived left atrial (LA) strain to detect early diastolic dysfunction in individuals with obesity and type 2 diabetes, and to explore the association between cardiac adipose tissue and LA function.Twenty patients with obesity and T2D (55 ± 8 years) and nineteen healthy controls (48 ± 13 years) were imaged using cine steady state free precession and 2-point Dixon cardiovascular magnetic resonance. LA function was quantified using a feature tracking technique with definition of phasic longitudinal strain and strain rates, as well as radial motion fraction and radial velocities.2, p < 0.001). There were significant correlations between LA functional indices and both BMI and EFV (p ≤ 0.007).Systolic left ventricular size and function were similar between the obesity and type 2 diabetes and control groups by MRI. All patients except four had normal diastolic assessment by echocardiography. In contrast, measures of LA function using magnetic resonance feature tracking were uniformly altered in the obesity and type 2 diabetes group only. Although there was no significant difference in intra-myocardial fat fraction, Dixon 3D epicardial fat volume(EFV) was significantly elevated in the obesity and type 2 diabetes versus control group (135 ± 31 vs. 90 ± 30 mL/mLA MRI-strain may be a sensitive tool for the detection of early diastolic dysfunction in individuals with obesity and type 2 diabetes and correlated with BMI and epicardial fat supporting a possible association between adiposity and LA strain.Trials Registration Australian New Zealand Clinical Trials Registry No. ACTRN12613001069741 Obesity and diabetes are strong risk factors for heart failure with preserved ejection fraction (HFpEF), a clinical syndrome that affects nearly half of patients with symptoms of heart failure . DiastolObesity and type 2 diabetes mellitus (ObT2D) commonly co-exist and together they contribute to a wide range of metabolic complications; importantly, they are increasingly recognised to be major contributors to the global burden of cardiac disease. The paucity of reliable early, non-invasive detection of diastolic changes on ObT2D population is therefore a key limitation of our current clinical and research capacity.The changes associated with the mid and late stages of diastolic dysfunction in individuals with obesity and T2D include a complex spectrum of adipose infiltration , fibrosis and electrophysiological alterations. Of these factors, intra-myocardial and epicardial fatty changes have received considerable attention. However, the relationship between cardiac fat and early dysfunction remains poorly understood. This deficit is largely attributable to the difficulties in detecting very early alterations in cardiac function.LA functional and volumetric changes are amongst the first imaging changes seen in ObT2D, and therefore may be a useful marker of early disease –8. RecenAlthough echocardiography is the generally accepted gold standard for measurement of atrial function and other diastolic functional or structural changes, in the setting of obesity the practical difficulties of imaging obese patients make routine acquisitions problematic. Cardiovascular magnetic resonance (CMR) may present a good alternative for reproducible, accurate and sensitive quantification of LA function. The recent development of feature tracking algorithms that can be applied in a semi-automated manner to CMR data permits myocardial strain measurements to be obtained from cine functional images –14. CMR In this study, we applied a novel MRI method for measuring atrial strain to detect subclinical evidence for diastolic dysfunction in a cohort of obese individuals with type 2 diabetes and no clinical evidence of heart failure. As a secondary aim, we assessed the association between abnormal atrial function and both intra-myocardial and epicardial fat.2 and known T2D (HbA1c ranged from 7 to 10% at study entry). Subjects were excluded if there was a contraindication to MRI or weight in excess of 150 kg (MRI table limit). Nineteen age and gender matched controls  with no history of cardiac disease were recruited. The local ethics committee approved the study and all patients provided written consent.The first 20 consecutive patients from the study entitled “The combined Effect of Liraglutide and Sleeve Gastrectomy on Metabolic, Cardiac, Neurological and Sleep Function in Obese Diabetes”  with a diagnosis of obesity and type 2 diabetes mellitus were recruited via the Department of Endocrinology, Diabetes and Metabolism at Royal North Shore Hospital, Australia. Inclusion criteria included BMI >30 kg/m2: 2.4, 4.8 ms). One patient and one healthy volunteer were excluded from the analysis as the Dixon images were not available.CMR data were acquired using a 1.5T Siemens Avanto scanner at North Shore Private Radiology, St Leonards, Australia. Cardiac volumes and left ventricle (LV) mass were quantified using 2-chamber (LVLA), 4-chamber (4CH), 3-chamber (LVOT) views and a short axis stack of cine SSFP images . 2-point Dixon data was also acquired  . LV end-t.The analysis and feature tracking algorithm has previously been described in details . It was R, SlC, SlA),  respectively. Longitudinal strain rates  and radial relative velocities  were computed, as the time derivatives of longitudinal and radial indices, for the three atrial functional phases: reservoir (S′), conduit (E′) and LA contraction (A′).Figure To further investigate the radial motion fraction modifications in term of LV related and LA standalone motions, this parameter was decomposed into two orthogonal components relative to the centre of the mitral valve (MV). The first, in the direction of the MV, was termed centric (cMr) and the other, normal to this direction . All continuous variables are expressed as mean ± standard deviation (SD). Normality was checked using the Shapiro–Wilk test. Differences between groups were considered significant for p < 0.05. Intra-observer was assessed using intra class correlation coefficient (ICC). Groups were compared using the independent-samples 2, range: 30–51 kg/m2); all individuals within the control group had a BMI < 30 kg/m2. At study entry, the ObT2D group had an average duration of T2Dof 11.4 ± 6.2 years and a mean HbA1c of 8.4 ± 1.1%.Table Echocardiographic diastolic data for the ObT2D group are presented in Table Table R), longitudinal strain rate (SRlS′), and radial motion fraction (MrR), were slightly reduced during reservoir phase in the ObT2D group compared to control and slightly increased for the atrial contraction phase . Both longitudinal strain and radial motion fraction were significantly reduced in the conduit phase . Expressed as an E′/A′ ratio, there was a 28.5% reduction in the longitudinal strain rate ratio . When radial motion was expressed as a relative velocity, the group difference was accentuated, with a 38.2% reduction in the VrE′/VrA′ ratio . The radial motion ratio was also increased by 12.7% .LA longitudinal strain . The increased cMrA in the ObT2D group corresponded to a magnitude change of +28% relative to controls . During the atrial relaxation (reservoir) and contraction phases, the MV centric radial components were higher in the ObT2D group compared to control . Following correction for BMI, these differences were attenuated but remained significant (p = 0.001).Intra-observer assessment resulted in an intra-class correlation coefficient of 0.95. Slight differences in intra-myocardial fat fraction were present between groups , VrE′/VrA′ and BMI (panel b), and VrE′/VrA′ and epicardial fat volume indexed to BSA (panel c). These demonstrated tight clustering of the VrE′/VrA′ values in the ObT2D group, with all of the subjects falling into the lowest two quartiles of VrE′/VrA′ , and 70% within the lowest quartile of the normal range. There was no overlap in BMI and almost no overlap in epicardial fat. Significantly, all subjects with a BMI over 30 kg/m2 had low values of VrE′/VrA′– below or near 1 standard deviation from the control group average value. Other significant associations between Dixon 3D epicardial fat fraction and functional LA indices are presented in Fig. E/SRlA, VrE/VrA, MrA, MrA/MrR). Correlation coefficients between functional indexes and BSA or Dixon 3D epicardial fat fraction are reported Table Figure E′/VrA′ in the control group . No other significant correlations were seen in either controls or in the ObT2D group . Figure E′/VrA′ in the ObT2D group, with values tightly clustered together. Therefore, linear correlation between BMI or epicardial fat was not performed to further analyse for any linear relationship. The ObT2D and control groups clearly did not form a normal distribution hence a pooled analysis was not performed.By univariate analysis, intra-myocardial fat was correlated to VrR and BSA  and between cMrR and BMI . Significant correlations were also found for indexed and non-indexed Dixon 3D epicardial fat volumes with cMrR  and pMrA . No significant correlations were present between atrial parameters and duration of diabetes or HbA1c.The correlations between MV centric radial motion fraction and adipose tissue quantifications and patient biology were highly significant between cMrOur data demonstrates that MRI-derived LA strain may be sensitive to early diastolic dysfunction. Our cohort of patients with obesity and T2D had an almost normal echocardiogram and non-enlarged LA volumes by standard imaging techniques . FurtherE′/SRlA′ and relative velocity VrE′/VrA′ ratios were significantly altered in the obese and diabetic group compared to matched controls, consistent with early stage diastolic dysfunction. Our data demonstrated a diminution of the conduit phase of LA function. A possible explanation for this finding could be elevated LV pressure, which is well described to be an early change in diastolic dysfunction. Coronary flow reserve has also been associated with LV filling pressure [E′/SRlA′) and radial (VrE′/VrA′) ratios depicted the change in the LA wall deformation, the passive conduit phase relative to the active phase of the LA. When radial motion was decomposed into cMr and pMr parts, the amplification of MV centric motion fraction during the LA contraction phase in the ObT2D group was consistent with the anticipated response of an early decrease in ventricular compliance impairing LV early filling. The observed reduction of reservoir MV corrected perpendicular motion fraction may related to LV contraction alterations as reported by Mochizuki et al. [Alterations of LA function in the ObT2D population are considered to be secondary to pressure overload and are associated with poorer LV systolic function and higher LV mass . Consistpressure  in ObT2Di et al. . An incri et al. , 20.An association between BMI and LA function has been previously described –23. In oThere are several proposed mechanisms by which the tissue alterations in obesity may influence the properties or mechanical load experienced by the LA. These include increased ventricular stiffness, inflammation mediated by adipokines, direct lipotoxicity or a metabolic effect mediated by insulin resistance . Diastolquantity. It is insensitive to other myocardial tissue organisational alterations occurring in obesity and T2D. Further data regarding other ultra-structural analysis  may be MRI is an attractive alternative to the routine use of echocardiography as it overcomes the practical problems of image attainment in obese patients and simultaneously characterises LA and LV functions as well as cardiac structure. The determination of cardiac fat volume by Dixon images has been previously reported . HoweverThis study has several limitations, including the relatively small sample size, slightly age range difference between patients and healthy volunteers, and uniform diagnosis of obesity and diabetes, which did not permit deconvolution of the contributions of these conditions. Additional studies are required on the decomposition of radial motion into centric and perpendicular motions. Our clinical evaluation of the control subjects was also limited and measured blood pressures were not available, a clinical diagnosis of any cardiovascular disease including hypertension was excluded for all controls. The quality of the myocardial characterisation could be improved with the addition of T1 mapping or magnetic resonance spectroscopy data. In order to explore the nature of the early changes occurring in obesity and T2D, prospective studies are needed that include longitudinal imaging time points combined with objective clinical and metabolic measures (e.g. glucose tolerance test) of the progressive metabolic disorders over time. Although the control echocardiographic data was not available in this study, from a methodological perspective, it would be useful to directly compare diastolic assessment by echocardiography between the controls and ObT2D groups.MRI-derived strain measurements may be a useful tool to detect early abnormal LA function. Our cohort of patients with obesity and T2D had near normal echocardiograms and MRI-derived LV systolic function and volumetric measures of the LA and LV, and we demonstrated clear reductions in the conduit to LA contraction ratios (E/A) for longitudinal strain rate and radial motion fraction. Importantly these atrial measures correlated to both epicardial fat and to BMI. Further work in larger cohorts with a greater dynamic range of these parameters is required to understand the full implications of these findings.


Scleroderma, known also as systemic sclerosis (SSc), is a severe disease associated with high mortality rates, and right ventricular (RV) remodeling and dysfunction, along with pulmonary artery hypertension (PAH), are among the most important internal organ manifestations of this disease. PAH has a higher prevalence in patients with SSc compared to the general population and represents a significant predictor of mortality in SSc. In patients with SSc, the morphological remodeling and alteration of RV function begin even before the setting of PAH and lead to development of a specific adaptive pattern of the RV which is different from the one recorded in patients with IAPH. These alterations cause worse outcomes and increased mortality rates in SSc patients. Early detection of RV dysfunction and remodeling is possible using modern imaging tools currently available and can indicate the initiation of specific therapeutic measures before installation of PAH. The aim of this review is to summarize the current knowledge related to mechanisms involved in the remodeling and functional alteration of the RV in SSc patients. Scleroderma, known also as systemic sclerosis (SSc), is a severe disease associated with high mortality rates, and right ventricular (RV) remodeling and dysfunction, along with pulmonary artery hypertension (PAH), are among the most important internal organ manifestations of this disease .The mortality of SSc depends primary on the burden of the internal organ involvement. Pulmonary hypertension (PH), pulmonary fibrosis, and kidney damage are the most frequent causes of death in SSc , 3. MyocSSc is a complex autoimmune disease characterized by a marked chronic inflammation, which leads to increased connective tissue fibrosis and vascular involvement causing severe damage of internal organs  and the skin .Activation of the immune system, linked with fibroblast dysfunction, T lymphocyte, macrophage, and mast cell disturbances induce the alteration of the extracellular matrix by secretion of cytokines, chemokines, growth factors, and other potent mediators resulting in excessive collagen deposit in the tissues . The exaThe various clinical form of SSc varies from limited cutaneous systemic sclerosis (lcSSc) or CREST  syndrome, to diffuse, sometimes fulminant forms with extended involvement of internal organs. The incidence of SSc greatly varies between different geographical regions and ethnic groups, with higher numbers among the African American population , 14. TheThe aim of this review is to summarize the current knowledge related to mechanisms involved in the remodeling and functional alteration of the RV in SSc patients.PAH has a higher prevalence in patients with SSc compared to the general population, being more commonly observed in patients with lcSSc form, and represents a significant predictor of mortality in SSc , 17. Curp = 0.01]), no such gain was observed in SSc-PAH patients, who also exhibited a worsening trend in tricuspid regurgitation jet velocity, right atrium (RA), and ventricular size , end-diastolic volume , and reduced ejection fraction (p < 0.0001) determined by 3DE. Doppler measurements showed increased systolic pulmonary artery pressure (sPAP) and pulmonary vascular resistance (tPVR) in SSc patients compared to the control group. These changes were more pronounced in patients with lcSSc form [Several studies tried to characterize RV involvement that occurs in SSc patients before development of PAH. Proper echocardiographic assessment of the RV function and volume estimation has been bound by its crescent shape, presence of intense trabeculations, and different contraction pattern, but novel techniques overcame these limitations . PigattoSSc form .p = 0.002), accompanied by decreased RV systolic function with significantly lower TAPSE and tissue Doppler maximum systolic myocardial velocity (RVS′), but no correlation was observed between these parameters. Right ventricle global longitudinal strain (RVGLS) was also significantly lower in SSc patients compared to the control group (p < 0.001). An inverse correlation was observed between duration of the disease and TAPSE and RVGLS [Durmus et al. used 2DSTE for the assessment of RV function in patients with SSc without PAH. Significantly higher sPAP  was recorded in SSc patients . No significant differences were recorded in terms of RV mass, RV-EDV, RV ejection fraction, stroke volume, or TAPSE between the two groups . It has p = 0.03). The abnormal RV-PA coupling and diminished force-frequency responsiveness (FFR) of these patients during exercise, along with reduced contractile and diastolic reserve, plead for the depletion of RV functional reserve of SSc-PAH patients. These results highlight the importance of intrinsic RV dysfunction, which ultimately leads to RV failure in SSc-PAH patients [The functional reserve of RV may also play an important role in the adaptive remodeling of the RV in SSc. Hsu et al. assessed RV function and morphology during exercise  testing in 15 SSc-PAH and 9 IPAH patients with comparable resting RV parameters. The RV contractility of the IPAH group was significantly increased during exercise, while the SSc-PAH group did not display improved contractility leading to important increase of RV-EDV and RV-ESV. The authors attribute these changes to decreased calcium cycling in the myocytes of SSc-PAH group (patients .p = 0.02) and PVR (p = 0.002) during exercise, with no changes in resting mPAP values. These findings illustrate the progressive nature of the disease and point out that alterations of exercise hemodynamic parameters precede the routinely determined resting values. The aforementioned changes might be related to the distinctive morphological and functional remodeling pattern of the RV in SSc patients [Kovacs et al. determined the pulmonary exercise hemodynamics of SSc patients with a 4-year follow-up period, observing significant increase of mPAP  .Given the high prevalence of RV impairment in scleroderma patients, current guidelines recommend early echocardiographic screening of SSc patients at risk for PAH. Immediate initiation of optimal therapy and prevention of right heart failure can improve the prognosis and survival of patients with SSc-PAH . TransthDifferent echocardiographic biomarkers have been proposed for characterization of RV function and can serve for evaluation of ventricular dysfunction in patients with SSc. TAPSE is an easily determinable parameter which is considered the most accurate in the assessment of the global RV contractility . It correlates with the parameters obtained from right heart catheterization and was proved as a prognostic factor in SSc-PAH , 54. AnoNovel echocardiographic modalities based on speckle tracking technology allow a better identification of subclinical heart failure. The technique is a software-based method that allows the calculation of tissue velocity and deformations of the myocardium derived from 2D images, tracking pixels (speckles) of a certain myocardial sector along the cardiac cycle. It can detect the changes in length of the tracked segment during systole and diastole with calculation of strain and strain rate (SR) parameters. These parameters offer an accurate, operator, and angle-independent view of the segmental and global (systolic and diastolic) function of the ventricles. Multiple studies suggest that RV longitudinal strain values and patterns are helpful in the assessment of RV function in SSc and PAH patients and correlate well with the prognosis of this patient category –61.The evaluation of the right ventricular function with nuclear imaging and scintigraphy can determine myocardial damage caused by SSc in early stages by identification of small perfusion defects. A ten-year survival study conducted by Steen et al. showed that SSc patients that presented perfusion defects upon scintigraphy examination with thallium presented a higher rate of cardiac disease and mortality . FurtherAlthough scintigraphy has been proven to be a sensitive method for detection of early perfusion defects in systemic sclerosis patients with no cardiac symptomatology, further studies are needed to elucidate its role in establishing prognosis and therapeutic management, which may be a hard task, since nuclear imaging methods present high costs and are not widely available.p < 0.001 and p < 0.009, resp.), and the RV ejection fraction matched for body surface area was significantly reduced in subjects with diffuse compared to limited cutaneous SSc [cMRI is a noninvasive imaging modality that faced a tremendous development in the last decade, being able to provide high quality images on the anatomy and function of the heart –68. cMRIeous SSc . Tzelepieous SSc . Their reous SSc .Hachulla et al. found that 75% of SSc patients presented cMRI abnormalities in their study population and that 21% of patients presented an altered RV ejection fraction, while 17% showed RV dilation in the absence of PAH. Moreover, they observed the thinning of the left ventricular myocardium that affected primarily patients with diffuse cutaneous SSc and those with no PAH, suggesting that this might be caused by disease's chronic effect on the microvasculature of the heart, being similar to the thinning that occurs during the ventricular remodeling process secondary to infarction .Magnetic resonance imaging of the heart is also a useful tool in evaluating the effects of various therapies in patients with PAH, as well as for prognosis implications. Allanore et al. have evaluated the effect of bosentan on the perfusion and function of the myocardium by performing cMRI and Tissue Doppler Echocardiography on 18 SSc patients with no PA and no symptoms of impaired cardiac function. The study found that cMRI perfusion index and the echocardiography parameters were improved after 4 weeks of bosentan administration . This shIn patients with SSc, the morphological remodeling and alteration of RV function begin even before the setting of PAH and lead to development of a specific adaptive pattern of the RV which is different from the one recorded in patients with IAPH. These alterations cause worse outcomes and increased mortality rates in SSc patients. Early detection of RV dysfunction and remodeling is possible using modern imaging tools currently available and can indicate the initiation of specific therapeutic measures before installation of PAH.


Several small studies have suggested that left atrial end-diastolic volume (LAEDV) is associated with adverse outcomes in patients with non-ischemic dilated cardiomyopathy (NICM). However, left atrial function, assessed through either LA end-systolic volume (LAESV) or the LA ejection fraction (LAEF) may provide incremental predictive utility. We sought to evaluate the prognostic value of LA volume and LAEF by Cardiovascular Magnetic Resonance (CMR) in a cohort of patients with NICM.117 patients  with NICM clinically referred for CMR were studied. Long axis cine images of the 2 and 4 chamber view were used to determine LAESV and LAEDV by a blinded reader using the area-length method. Values were indexed to body surface area using the Mostellar formula. Calculation of left ventricular (LV) volumes and EF were performed and the presence of any LV late gadolinium enhancement (LGE) was scored by an independent reader. All patients were followed for the composite outcome of cardiac death or appropriate implantable cardiac defibrillator (ICD) therapy. Cox proportional hazards models and Kaplan-Meier analysis were used to examine associations between LA measurements and the composite outcome.2 , LAESVi: 1.52 per 10 ml/m2 , and LAEF: 0.66 per 10% . These measures remained independently associated with the composite outcome following adjustment for ICD implantation and LVEF with HRs of 1.33 (p = 0.01), 1.51 (p < 0.01), and 0.66 (p < 0.01), respectively. A multivariable model that replaced LVEF with presence of LGE as an independent variable showed similar results with HRs of 1.30 (p = 0.04), 1.47 (p < 0.01), and 0.68 (p = 0.01), respectively. Kaplan-Meier analysis showed only LAEF to have significant predictive value for event free survival (p = 0.04).Mean age was 57.1 ± 14.0 years and mean LVEF 31.8 ± 12.1%. Over a median follow-up of 689 days, 19 patients developed the composite outcome. In univariable analysis, ICD implantation, presence of LGE, LVEF, LAEDV, LAESV and LAEF were significantly associated with the composite outcome. Following adjustment for ICD implantation, hazard ratios (HRs) for each of the LA measurements were; LAEDVi: 1.32 per 10 ml/mBoth LA volume and LAEF are associated with the occurence of cardiac death or appropriate ICD therapy among patients with NICM. However, LAEF is superior for the discrimination of event free survival and may therefore be a preferred measure of risk in this population.


The tricuspid annular plane systolic excursion (TAPSE) increased from 16.5 mm to 18.9 mm after 12 months. MitraClip implantation improves pulmonary artery pressure, tricuspid regurgitation, and TAPSE after 12 months. At the same time, there is a decrease in the RVOT diameter without significant changes in other right ventricular and right atrial dimensions.Positive results of MitraClip in terms of improvement in clinical and left ventricular parameters have been described in detail. However, long-term effects on secondary pulmonary hypertension were not investigated in a larger patient cohort to date. 70 patients with severe mitral regurgitation, additional pulmonary hypertension, and right heart failure as a result of left heart disease were treated in the heart centers Hamburg and Göttingen. Immediately after successful MitraClip implantation, a reduction of the RVOT diameter from 3.52 cm to 3.44 cm was observed reaching a statistically significant value of 3.39 cm after 12 months. In contrast, there was a significant reduction in the velocity of the tricuspid regurgitation (TR) from 4.17 m/s to 3.11 m/s, the gradient of the TR from 48.5 mmHg to 39.3 mmHg, and the systolic pulmonary artery pressure (PAPsyst) from 58.6 mmHg to 50.0 mmHg. This decline continued in the following months (V Mitral regurgitation is the second most common cause of heart valve failure in Europe  and leadWhile an acute pressure increase in the pulmonary veins leads to pulmonary edema, chronic congestion often ends in reactive pulmonary vasoconstriction with consecutive secondary pulmonary hypertension. Alongside the degree of mitral regurgitation, other factors, such as severe impaired left ventricular ejection fraction, may also have an impact on secondary pulmonary hypertension –4.Previous published data demonstrate an important prognostic effect on perioperative course of right ventricular function and hemodynamics in patients with impaired left ventricular ejection fraction and pulmonary venous hypertension , 6. EchoPatients with chronic heart failure due to ischemic or dilated cardiomyopathy often undergo surgical revascularization or cardiac valve surgery to improve the left ventricular function. In large surgical cohorts, an influence of the secondary right heart failure solely by correction of mitral valve insufficiency was often associated with inconstant outcomes and increased mortality and morbidity –12.Positive results of a MitraClip implantation in terms of an improvement in clinical and left ventricular parameters have been described in detail in the current literature , 14. PulPatients with severe mitral regurgitation have been treated in the heart centers of Hamburg and Göttingen since 2009, using the MitraClip procedure. Anonymized clinical and epidemiological data were scientifically evaluated after written informed consent by the patient. The current study was done in accordance with national and international guidelines and the Declaration of Helsinki after approval by the local ethical committees.Between 2009 and 2015, 70 patients with severe mitral regurgitation were treated in both cardiac centers, using MitraClip where additional pulmonary hypertension was present due to left heart disease. In addition, clinical signs of right heart failure, for example, edema or aszites, had to exist. Patients with pulmonary hypertension or right heart failure from other causes such as chronic thromboembolism (CTEPH) or unclear or multifactorial mechanisms were excluded from the current analysis.To estimate the pulmonary artery pressure, the presence of a measureable tricuspid regurgitation was necessary. Additionally, evaluable echocardiographic data for each patient had to be available, prior the MitraClip implantation, before hospital discharge after successful implantation, and again after twelve months.All transthoracic echocardiography readings were made during clinical routine and digitally stored, so that subsequent measurements and evaluations were possible. A retrospective echocardiographic analysis took place in accordance with the recommendations of the American and European scientific societies , 18. ParRV dimensions and tricuspid valve parameters were quantified from the apical four-chamber view. LVOT diameters were measured in the parasternal outflow view and inferior vena cava diameters in the subcostal view.Vmax) and this value was used in the modified Bernoulli equation . For the right atrial pressure (RAP), a value of 5 mmHg at complete collapse of the inferior vena cava was applied as well as a value of 10 mmHg at a partial collapse and a value of 15 mmHg in the absence of collapse [P + RAP [The estimation of systolic pulmonary artery pressure (PAPsyst) was carried out by a continuous-wave Doppler determination of the maximum velocity of the tricuspid regurgitation . Differences in echocardiographic measurements were calculated using Wilcoxon paired signed-rank test. A value of P < 0.05 was considered statistically significant.Statistical analysis was performed with the Statistical Computing Software R , yet without becoming significant again compared to the values determined at discharge (The systolic and diastolic distance measurements of the TV annulus and the determination of the TR-Regurgitation area compared to the other time points remained unchanged within the observation period. Immediately after successful intervention, the vena contracta of the TR diminished from 0.88 cm to 0.82 cm, according to the RVOT. But a statistically significant value of 0.77 cm was reached after 12 months. In contrast, immediately after the intervention, there was a significant reduction in the maximum velocity of the TR from 4.17 m/s to 3.11 m/s, of the maximum gradient of the TR from 48.5 mmHg to 39.3 mmHg, and of the systolic pulmonary artery pressure from 58.6 mmHg to 50.0 mmHg. This decline continued in the following months (ischarge . Though,ischarge . HoweverOur results demonstrate that a significant reduction in systolic pulmonary artery pressure and the flow velocity of the tricuspid regurgitation follows immediately after successful MitraClip implantation. A Swiss research group observed a comparable immediate effect on the pulmonary artery pressure . Both thHowever, in contrast to the above parameters, no significant decrease of the remaining right ventricular and atrial diameters could be documented in our patient cohort, even in the extended follow-up period of twelve months. The width of the tricuspid valve ring and the diameter of the inferior vena cava did not change in our group either. The reason for this is not clear. To what extent an even longer follow-up period of two or more years would result in significant changes remains speculative and should be investigated by further multicenter long-term studies.Mitral Valve Repair by MitraClip improves the pulmonary artery pressure and tricuspid regurgitation in preexisting secondary pulmonary hypertension after 12 months. At the same time, there is a decrease in the diameter of the right ventricular outflow tract without significant changes in other right ventricular and right atrial dimensions. The TAPSE as a sign of right ventricular function also improves significantly within the follow-up period.


We report the first patient experiences with the CardioMEMS device in the Erasmus MC Thorax Center in the Netherlands. In line with clinical trial evidence, the device is applicable in patients with chronic heart failure in functional New York Heart Association class III with at least 1 admission for heart failure in the past 12 months. CardioMEMS has been shown to be safe and reliable, and effective in reducing the number of hospitalisations for heart failure by guided therapy based on pulmonary artery pressures. We present a case of a 59-year-old male patient with a history of diabetes mellitus and an anterolateral myocardial infarction in March 2016 for which a percutaneous coronary intervention (PCI) of the left anterior descending artery and left circumflex artery was performed. Initial echocardiogram demonstrated a severely depressed left ventricular function with an ejection fraction of 15% and severe mitral insufficiency. The patient was decongested with diuretics and treated with standard heart failure medication according to guidelines. He developed low cardiac output syndrome with prerenal renal insufficiency with minor changes in angiotensin converting enzyme (ACE) inhibitor dosages and orthostatic symptoms. The balance between stable heart failure, renal insufficiency and adequate dosages of heart failure (HF) treatment was delicate but finally achieved. We performed a Swan-Ganz right heart catheterisation with no pulmonary hypertension and normal pulmonary capillary wedge pressure. At the outpatient clinic, heart failure medications were titrated to maximum tolerance. Due to development of dry cough, we switched Ramipril to valsartan with relieve of cough but prerenal renal insufficiency remained, with an estimated glomerular filtration rate (eGFR) of 35–45. Six months later, follow-up echocardiogram demonstrated a severely depressed left ventricular function and signs of elevated right heart pressures. Due to progressive renal insufficiency, we switched valsartan to hydralazine and intensified isosorbide dinitrate and diuretics. The patient’s functional New York Heart Association (NYHA) class was III and a VO2max was performed with a score of 16 ml/kg/min. At this stage, we admitted the patient to examine the pulmonary hypertension. There were no options to increase diuretics as the patient was euvolemic and suffered from prerenal moderate renal insufficiency. Invasive Swan-Ganz measurement confirmed the estimated pressures on echocardiogram with a pulmonary artery (PA) systolic pressure of 87 and a PA diastolic pressure of 34 (mean PA pressure 52 mm Hg). We decided to offer the patient a new device (CardioMEMS) to monitor his pulmonary pressures remotely with respect to treatment alterations which were previously difficult to achieve based on physical examination, weight and blood values alone.The CardioMEMS device is an implantable wireless system for continuous monitoring of PA pressures which has been shown to be safe and reliable and clinically effective in reducing HF associated hospitalisations in the CHAMPION trial . Complicp-value < 0.0001). Several centres in the Netherlands have been asked to participate in a post-marketing surveillance programme from Germany. The Erasmus Medical Center has performed multiple procedures, so far successfully, with comparable clinical outcome as presented by the example in this case. CardioMEMS is currently only available in a study environment and not available as standard care in the Netherlands, nor is it covered by medical insurance.The CHAMPION trial included patients with chronic heart failure NYHA class III, irrespective of left ventricular ejection fraction and a previous HF hospitalisation. The trial randomised 560 patients to wireless implantable haemodynamic monitoring versus standard care alone. In 6 months, a significant reduction in hospitalisations for HF was demonstrated compared with the control group , individualised patient care via telemonitoring can change the clinical practice for physicians, specialist heart failure nurses and, most importantly, patients.


In diabetic cardiomyopathy (DCM), ventricular remodelling consists in a progressive impairment of myocardial contraction (evolving from diastolic to combined diastolic-systolic dysfunction) occurring regardless of ischemic heart disease, hypertension or other macrovascular complications, which ultimately leads to heart failure. Early stages of DCM are asymptomatic and characterised by initial contractile disfunction and various degree of myocardial fibrosis, that may not be recognised by traditional cardiology tests. Our purpose was to detect myocardial fibrotic infiltration in DM-II patients by using T1-mapping technique with extracellular volume fraction (ECV) measurement.Forty diabetic patients  with preserved ventricular function and no history of ischemic cardiopathy and 20 controls underwent to CMR. Imaging protocol included: modified Look-Locker sequence before and 20 minutes after 0.2 mmol/kg gadoterate meglumine injection; T2 mapping; ventricular function module; conventional T2-weighted and late gadolinium enhanced (LGE) imaging. Global native T1 (nT1), T2 and ECV values were calculated and correlated to clinical features such as symptoms, glycated haemoglobin (HbA1c), duration of disease and therapy. Pearson Correlation, Mann-Whitney test and unpaired T-test were used for statistical analysis.Patient group had higher nT1 and ECV values compared to controls , whereas no significant differences occurred in T2 measurements .nT1 and ECV showed direct correlations with HbA1c  and disease duration  in diabetic patients. An inverse correlation was found between T2 and HbA1c .Areas of ischemic LGE were found in two patients as marker of silent infarction.Diabetic patients with preserved ventricular function have increased nT1 and ECV as reflection of silent slight inflammation and diffuse myocardial fibrosis, which degree correlates with HbA1c and disease duration.


Acute heart failure is a common reason for hospital admission and is usually caused by decreased cardiac output either as a result of an intrinsic cardiac issue or as a result of severe hypertension with elevated afterload. We present a patient with a history of HFrEF who presented with acute heart failure, found to have hypotension requiring Dobutamine support and an elevated systemic vascular resistance requiring Nicardipine drip, with subsequent recovery of cardiac function. Heart failure is a clinical syndrome characterized by a decrease in cardiac output with or without an increase in intracardiac pressure, which can be caused by structural or functional pathologies. One of the determinants of cardiac output (CO) is afterload, which is the force that the heart must overcome to pump blood to the body . SystemiA 53-year-old lady with history of HTN, initially characterized by HFpEF which progressed to HFrEF, presented with heart failure exacerbation secondary to medication noncompliance. Vital signs on admission included temperature 98.6F, BP 127/83, HR 92, RR 18, and O2 sat 93% on 2 L nasal cannula. Echocardiogram showed a LVEF of 25–30% with Grade 2 diastolic dysfunction. Intravenous diuresis was initiated with development of hypotension. Dobutamine was started but was unable to be weaned off. Left heart catheterization revealed no evidence of CAD. Right heart catheterization results are shown in Heart failure has a prevalence of over 5.8 million people in the United States and greater than 23 million people around the world [∗ SVR.This patient's profile is a unique blend between a patient with hypertensive emergency presenting with heart failure exacerbation requiring vasodilators such as Nicardipine and someone in a low cardiac output state requiring inotropic support. The likely pathophysiology of this patient's presentation is that she had a “hypertensive emergency,” because of her baseline reduced EF, resulting in the inability to compensate for the elevated SVR, which, in turn, resulted in hypotension. This is in line with the formula for Mean Arterial Pressure: MAP = CO Vasodilators help with heart failure as they decrease left ventricular filling pressures. This can increase cardiac output as the stroke volume will increase due to decrease in SVR and then result in decreased myocardial oxygen demand . CalciumAroney et al. studied the inotropic effect of Nicardipine in acute heart failure. The study included 15 patients with heart failure with reduced ejection fraction (0.15 ± 0.02), NYHA II to IV. These patients received equihypotensive doses of IV Nitroprusside and IV Nicardipine. The patient's baseline values were obtained followed by infusion of Nitroprusside, returning to a second baseline, followed by Nicardipine infusion. LV pressure volume loops showed a rightward shift with Nicardipine, suggestive of negative inotropic effect. Overall this study suggested an increase in Cardiac Index, decrease in SVR, and increase in LV ejection fraction with Nicardipine .Management of patients with such heart failure requires the use of vasodilators which help increase CO by decreasing SVR, with the aid of inotropes to maintain the BP as the SVR decreases. The above combination helped our patient to avoid chronic inotropic support and further advanced heart failure care including mechanical assist devices or heart transplant. To the best of our knowledge, this is the first case in which a patient with acute heart failure exacerbation with cardiogenic shock benefited from the combination of Dobutamine for inotropic support and Nicardipine for improvement in SVR.In patients with a known history of hypertensive heart disease presenting with acute heart failure and cardiogenic shock, a low cardiac output due to increased systemic vascular resistance may exist. Measurement of the SVR may lead to the use of vasodilator therapy, in combination with inotropes, which may lead to resolution of the heart failure.