Athletic cardiac remodeling can occasionally be difficult to differentiate from pathological hypertrophy. Detraining is a commonly used diagnostic test to identify physiological hypertrophy, which can be diagnosed if hypertrophy regresses. We aimed to establish whether athletic cardiac remodeling assessed by cardiovascular magnetic resonance is mediated by changes in intracellular or extracellular compartments and whether this occurs by 1 or 3 months of detraining.Twenty-eight athletes about to embark on a period of forced detraining due to incidental limb bone fracture underwent clinical assessment, ECG, and contrast-enhanced cardiovascular magnetic resonance within a week of their injury and then 1 month and 3 months later.P<0.0001), increase in native T1 , and extracellular volume fraction  with no further changes by 3 months. The decrease in LV mass was mediated by a decrease in intracellular compartment volume  with no significant change in the extracellular compartment volume. High LV mass index, low native T1, and low extracellular volume fraction at baseline were all predictive of regression in LV mass in the first month.After 1 month of detraining, there was reduction in left ventricular (LV) mass (130±28 to 121±25 g; Regression of athletic LV hypertrophy can be detected after just 1 month of complete detraining and is mediated by a decrease in the intracellular myocardial compartment with no change in the extracellular compartment. Further studies are needed in athletes with overt and pathological hypertrophy to establish whether native T1 and extracellular volume fraction may complement electrocardiography, echocardiography, cardiopulmonary exercise testing, and genetic testing in predicting the outcome of detraining. Regular athletic training leads to physiological cardiac adaptation, namely biventricular dilatation and left ventricular hypertrophy, sometimes termed athlete’s heart. Cross-sectional studies using cardiovascular magnetic resonance T1 mapping imply that athletic left ventricular hypertrophy is mediated by an increase in the intracellular compartment (predominantly myocytes), with a relatively constant extracellular compartment (extracellular matrix and capillary vasculature). We studied athletes who were about to embark on a period of forced detraining due to incidental limb bone fracture within a week of their injury and then 1 month and 3 months later. On complete detraining, athletic left ventricular hypertrophy regressed within a month, which was mediated by decrease in the size of the cellular compartment with no change in the extracellular compartment. T1 mapping is a powerful tool to investigate mechanisms and reversibility of hypertrophy in athletes and may have a role in predicting the outcome of detraining. However, it remains to be validated in athletes with abnormal ECG and suspected cardiomyopathy.1 LV hypertrophy that overlaps into the pathological range is relatively rare although it does occur more commonly in participants of certain sports such as rowing and cycling and in male and black athletes.2The regular training that is required to participate in competitive sport leads to physiological cardiac adaptation, namely biventricular dilatation and left ventricular (LV) hypertrophy, sometimes termed athlete’s heart.4 These cross-sectional findings imply that athletic LV hypertrophy is mediated by an increase in the intracellular compartment (predominantly myocytes), with a relatively constant extracellular compartment (extracellular matrix and capillary vasculature). Conversely, areas of hypertrophy in hypertrophic cardiomyopathy (HCM) have increased ECV, and initial data suggest that this divergent pattern might be useful to differentiate it from athlete’s heart.5Cardiovascular magnetic resonance (CMR) is commonly used in the assessment of athletes with LV hypertrophy because it allows both visualization of the LV in multiple imaging planes and detection of focal scar by late gadolinium enhancement (LGE) imaging. T1 mapping by CMR has been proposed to investigate cardiac tissue characteristics in athletes. Athletes have lower cardiac extracellular volume fraction (ECV) than sedentary controls, and the fittest athletes have the lowest ECV.7Neither native T1 nor ECV has been validated histologically in athletic hypertrophy. However preclinical models of athlete’s heart have shown that increase in LV mass in exercise-trained rats is not associated with increase in collagen fraction, therefore, implying it is mediated by increase in myocyte mass.8 A minimum of 3 months of detraining is typically required to demonstrate regression of LV hypertrophy albeit with reduction in training rather than complete cessation.10 Compliance with detraining is often poor, and it is unpopular with athletes of all levels. There is, therefore, a need to improve the identification of athlete’s heart by noninvasive imaging and predict the outcome of detraining.Detraining is a commonly used test to diagnose athletic remodeling, although data supporting its use are limited. After long-term cessation of training, regression of hypertrophy and dilatation occurs in 80% of athletes with cardiac dimensions outside the normal range.We hypothesized that in athletes who completely stop all forms of training, regression of LV hypertrophy occurs in 1 month and is mediated by a decrease in intracellular compartment volume. We aimed to investigate whether T1 mapping findings at baseline are predictive of the cardiac consequences of detraining.The data that support the findings of this study are available from the corresponding author on reasonable request. We prospectively recruited athletes presenting to the Emergency Department in Leeds Teaching Hospitals NHS Trust with a limb bone fracture for which they were advised to stop training for a minimum of 6 weeks. Only athletes aged 18 to 45 years who trained for >4 hours a week for >2 years were recruited. Exclusion criteria were any significant medical history, any regular medication, or self-reported use of anabolic steroids. Some athletes were able to recommence light training (fewer hours and lower intensity than preinjury levels) before their 3-month appointment, and this was not prohibited by the research team. The study was approved by the National Research Ethics Service (16/EM/0399), and all participants gave written informed consent.11 LV mass was estimated from ECG by the Sokolow-Lyon product, the voltage sum of the greatest S wave in V1/2 and R wave in V5/6.12 A full blood count, for measurement of hematocrit, was taken at the time of intravenous cannulation before each CMR study.Appointments occurred within a week of the injury, 1 month and 3 months later. At each appointment, athletes underwent clinical assessment, contrast-enhanced CMR, and 12-lead ECG. Twelve-lead ECG  was analyzed by 2 physicians blinded to clinical details according to international guidelines for ECG interpretation in athletes.Participants underwent CMR on a dedicated cardiovascular 3-Tesla Philips Achieva system equipped with a 32-channel coil and MultiTransmit technology. Data were acquired during breath holding at end expiration. Balanced steady-state free precession cine images covering the entire heart in the LV short axis were acquired before contrast administration .T1 maps were acquired in 3 short-axis slices. Native T1 mapping used a breath-held modified Look-Locker inversion recovery acquisition  3 s; single-shot, SENSE factor 2; prepulse delay, 350 ms; trigger delay set for end diastole [adaptive]; flip angle, 20°; matrix, 400×400; slice thickness, 10 mm; giving a reconstructed voxel size of 1.17×1.17 mm).Gadobutrol (0.15 mmol/kg) was administered through an intravenous cannula with a 10-mL saline flush .3; tag separation, 7 mm; ≥18 phases; repetition time, 5.8 ms; echo time, 3.5 ms; flip angle, 10°; typical temporal resolution, 55 ms) was acquired in the 3 short-axis slices.13Tissue tagging by spatial modulation of magnetization  3 s (3 s) 2 s modified Look-Locker inversion recovery acquisition with identical positioning and planning to the native T1 map.14 LGE imaging was analyzed visually to assess for the presence of scarring.CMR data were assessed quantitatively using commercially available software blinded to detraining status . Epicardial and endocardial borders were traced offline on the short-axis cine stack at end diastole and end systole to calculate LV and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume, stroke volume, ejection fraction, and LV mass. Papillary muscles were excluded from all measurements. Indexed cardiac parameters were divided by body surface area calculated by the Mosteller equation at baseline.15Pre- and postcontrast myocardial T1 values with a 3-parameter exponential fit with Look-Locker correction were measured from short-axis slices in the septum. Average measurements from the basal and mid ventricular slices were used. Data from the apical slice was not used because it was vulnerable to partial volume effects because of decreased wall thickness. ECV was calculated from native and postcontrast T1 times of myocardium and blood pool and hematocrit as reported previously.16Intracellular compartment volume was calculated by multiplying (1−ECV)×(LV mass/1.05). Extracellular compartment volume was calculated by multiplying ECV×(LV mass/1.05).13 Peak LV circumferential strain was measured for the 3 slices.Tagging analysis was conducted using inTag . Endocardial and epicardial contours were drawn on the short-axis spatial modulation of magnetization sequences using a semiautomated process as reported previously.t test. When comparing 3 paired groups, ANOVA with repeated measures was used. P<0.05 was considered statistically significant.Statistical analysis was performed using IBM SPSS Statistics 22.0 . Continuous variables were expressed as mean±SD or median (interquartile range) depending on normality. Categorical variables were expressed as n (%). Paired data at baseline 1 and 1 month were compared by paired 17Receiver operating characteristic analysis was used to determine the diagnostic accuracy baseline imaging parameters to predict regression of LV hypertrophy (>10 g) or cavity dilatation (>10 mL). The diagnostic accuracy is expressed as area under the curve and 95% CI. Optimal sensitivity and specificity were calculated using Youden index. Variables were combined by binary logistic regression. Areas under the curve were compared by using validated methods described by DeLong et al.2, a minimum sample size of 25 athletes would be required .3The study was powered to detect a 7.5% decrease in indexed intracellular compartment volume after 1 month of detraining. Assuming that baseline indexed intracellular compartment volume would be comparable to low-performance athletes in our previous study, which was 47±6 mL/mThirty-five athletes agreed to take part in the study between November 2016 and March 2018. One athlete was unable to complete the study because of claustrophobia, 1 withdrew because of possible pregnancy, and 5 withdrew consent after the first scan but before the second scan. The final cohort of 28 included 23 male and 5 female athletes with a median age of 24  years. Twenty-three athletes completed the whole protocol, with 5 athletes withdrawing after their 1-month scan because they had resumed full training. Baseline characteristics and their progression throughout the study are shown in Table 5 and the Sokolow-Lyon product, both electrical markers of LV mass  reduction in LV mass with no further reduction between 1 and 3 months  with no significant change in the extracellular compartment mass . By 3 months of detraining, there was no further decrease in EDV of either ventricle . There were no further changes at 3 months.After 1 month of detraining, there were nonsignificant absolute increases in peak circumferential strain in all 3 levels .Between the 1- and 3-month scan, 11 of 23 athletes were able to restart light training but were still not able to resume full training. When athletes were split according to those who had resumed light training (n=11) and those who had not (n=12), there was no difference in any LV or RV volumetric parameter, native T1, or ECV . The difference in diagnostic accuracy between LV mass index and native T1 (P=0.58) or ECV (P=0.71) was not significant. When LV mass index was combined with either native T1 or ECV by a binary logistic model, there was an improvement in diagnostic accuracy (Table II in the Data Supplement). None of LV EDV index, native T1, or ECV were predictive of absolute LV EDV regression in 1 month of detraining of >10 mL. Only RV EDV index, but not native T1 or ECV, was predictive of absolute RV EDV regression in 1 month of detraining of >10 mL.High LV mass index, low native T1, and low ECV at baseline were all predictive of an absolute LV mass regression in 1 month of detraining of >10 g  with no change in extracellular compartment volume. High baseline LV mass is the strongest predictor of regression of LV hypertrophy after 1 month of detraining. Low native T1/ECV was also predictive of LV mass regression at 1 month and may have a role in the diagnosis of athlete’s heart.4 These studies were cross-sectional and, therefore, cannot be used to attribute causality. Our present study is the first to show a longitudinal relationship between LV mass, ECV, and training, confirming the hypothesis that athletic hypertrophy is mediated by an increase in the cellular compartment.We have demonstrated that regression in LV mass is mediated by a decrease in the intracellular myocardial compartment with no change in the size of extracellular compartment. Previous studies have demonstrated that athletes have lower ECV than sedentary controls and that the fittest athletes have the lowest ECV.18 and there is regression of both the cellular and extracellular compartments after aortic valve replacement.16When T1 mapping data and LV mass are combined, it is possible to dichotomize the myocardium into cellular and extracellular compartments. This pattern is particularly relevant in hypertrophic phenotypes and has been validated most comprehensively in aortic stenosis; where the derived extracellular compartment volume has a strong correlation with diffuse fibrosis on biopsy20 High-level athletes with HCM are reported to have an altered phenotype with more prominent cavity dilatation, but replacement fibrosis is still identified in 33%.21 In HCM, focal fibrosis is progressive, and the extent of LGE increases progressively during the course of the disease.22 Saberi et al23 performed a study of 113 patients with HCM who were randomized to a 16-week programme of moderate-intensity exercise or standard care. They reported that exercise training led to increased exercise capacity but did not change ventricular volumes or the extent of focal fibrosis on LGE.The most important differential diagnosis in the young athlete with LV hypertrophy is HCM. CMR tissue characterization has been histologically validated in HCM and can be used to detect both diffuse fibrosis (increased ECV) and replacement fibrosis .It would be appealing to conduct a study of detraining in high-level athletes with HCM to investigate reversibility of changes in cellular and extracellular compartments. However, in practice, such a study would be almost impossible given the small number of patients with HCM who participate in competitive sport and their low willingness to voluntarily detrain.7 Benito et al24 trained rats to run on a treadmill for an hour a day. After 8 weeks of training, there was an 11% increase in LV mass but no alteration in the hydoxyproline  content of the whole LV. These results are in keeping with our finding that athletic hypertrophy is mediated by preferential expansion of the intracellular compartment.T1 mapping in athlete’s heart has not been validated histologically. However, there are preclinical rat models of exercise-induced cardiac hypertrophy, which suggest physiological hypertrophy is not mediated by increase in myocardial collagen.25 Arbab-Zadeh et al26 demonstrated in a longitudinal study of 12 previously sedentary subjects when trained for endurance sport development of cardiac athletic remodeling, albeit to a lesser extent than that seen in elite athletes. They reported that in the first 3 months of training, there were significant increases in RV EDV and LV mass with increase in LV EDV by 6 months. Most of the subjects were training for the marathon, and it is not known whether these longitudinal patterns of remodeling apply to other sports or training regimes. Cardiac hypertrophy regression with detraining in our study was quicker, taking only 1 month, compared with remodeling on commencement of training, which took at least 3 months in the previous study.26 Although it should be noted that the previous study did not conduct imaging at 1 month and participants in both studies conducted different sports with different baseline fitness.Previous studies have demonstrated that the heart is highly adaptable to physical training, and cross-sectional studies have clearly demonstrated a dose-response relationship between degree of fitness (measured quantitatively by cardiopulmonary exercise test) and extent of LV and RV remodeling.9 reported that LV mass measured by echocardiography in 6 Olympic rowers/canoeists decreased by 75 g (24%) in a voluntary period  of detraining following the 1988 Seoul Olympic Games. Weiner et al10 reported a significant regression in LV mass of 4 college American Football players with LV hypertrophy after 3 months of voluntary detraining that returned to pretraining level by 6 months. In a cohort of 40 Olympians, Pellicia et al8 reported a 28% reduction in LV mass after long-term detraining (1–13 years). These studies included athletes with LV hypertrophy at baseline (>12 mm interventricular septum) and included athletes at the pinnacle of fitness. The LV hypertrophy was more pronounced in these studies than ours, reflecting the fitness of the athletes studied. The extent of LV mass regression was, therefore, greater (24%–28% versus 7%). These studies defined detraining as reduction in exercise intensity rather than complete cessation, perhaps explaining why regression of LV mass not reported until 3 months.The evidence of regression of athletic ventricular remodeling with detraining largely predates CMR, and studies were conducted by echocardiography. Maron et al27 performed echocardiography in 21 amateur runners after an 18-week training programme and then after 4 and 8 weeks when participants were limited to <2 hours of training a week. Similar to our findings, they reported a 10.4% reduction in LV mass after 4 weeks with no change in LV EDV even 8 weeks post-race.Pedlar et al28 and by echocardiography in astronauts (n=38) immediately after a 9- to 16-day spaceflight.29The finding of early regression of LV mass is not unique to athletes and has been reported in by CMR in healthy individuals (n=5) after 6 weeks of complete voluntary bed rest2max of 60±8 mL/kg per min. If we had been able to recruit higher performance athletes with higher LV mass at baseline, we may have been able to detect a further decrease in LV mass between 1 and 3 months. An alternative explanation is that the pattern of regression reflects the nature of detraining. Athletes were most incapacitated immediately after their fracture leading to most regression in this period. Throughout the subsequent recovery, the levels of physical activity gradually increased affecting the regression response.The mean LV mass in the present study (130±28 g) was comparable to low-performance male athletes in our previous study (129±17 g) who had a mean VO13 In the current study, we found that in all 3 levels, there was a no significant increase in strain on detraining, despite significant decreases in LV mass and intracellular compartment in the same period.Using the same CMR tagging methodology, we have previously shown that athletes have lower peak circumferential strain than sedentary controls.In this study, we relied on self-reported abstinence from training, and it is, therefore, possible that athletes performed training that was not reported to the research team. We have not conducted an objective assessment of fitness using cardiopulmonary exercise test, but this was not possible because of the nature of the participants’ injuries. Athletes in this study participated in a range of sports giving different patterns of athletic remodeling at baseline. We did not collect data on nonsteroidal anti-inflammatory use, which may have caused fluid retention and altered the myocardial extracellular compartment. We have not studied athletes with an abnormal ECG, overt LV hypertrophy (12–15 mm), or cardiomyopathy, and patterns of regression in these groups remain to be established.30T1 mapping has only been validated histologically in disease and is difficult to validate in athlete’s heart. Native T1 (and less so ECV) varies by field strength, manufacturer, and pulse sequence. At present, it is recommended that normal values specific to the scanner and acquisition protocol are used to determine ECV in the athlete with unexplained LV hypertrophy.Regression of athletic LV hypertrophy can be detected after just 1 month of complete detraining and is mediated by a decrease in the intracellular myocardial compartment with no change in the extracellular compartment. Further studies are needed in athletes with overt and pathological hypertrophy to establish whether native T1 and ECV may complement electrocardiography, echocardiography, cardiopulmonary exercise testing, and genetic testing in predicting the outcome of detraining.


A wide spectrum of cardiac arrhythmias has been observed in patients with isolated ventricular non-compaction, which is defined by hypertrabeculated ventricular myocardium with deep intertrabecular recesses, in the absence of concomitant congenital heart disease. In this genetically diverse phenotype, the development of fibrosis contributes to an arrhythmogenic substrate underlying atrioventricular conduction diseases, supraventricular tachycardias and ventricular tachycardias. Within this spectrum, monomorphic ventricular tachycardia is the most frequently observed arrhythmia, and this prevalence has important implications for sudden cardiac death risk. Specifically, LVNC exists in the absence of other congenital heart defects.2 This rare cardiomyopathy has a reported prevalence of 0.05% to 0.25% in adults.3 A wide spectrum of cardiac arrhythmias has been described in case reports and series, which are discussed in this article.Isolated left ventricular non-compaction (LVNC) is a cardiomyopathy defined by hypertrabeculation of the ventricular myocardium, and was first described in 1990.. The criteria for the diagnosis of LVNC of left ventricular myocardium on transthoracic echocardiogram (TTE) were: (1) the presence of many excessively prominent trabeculations; and (2) an absence of coexisting cardiac abnormalities. The ratio of compacted (epicardium to trough of trabeculations) to non-compacted myocardium (trough to peak of trabeculations) was evaluated at the levels of the mitral valve, papillary muscles, and apex at end-diastole, and compared with normal values for patients in the same age range; LVNC was defined by the ratio of compacted to non-compacted tissue ≤ 0.5.1In the first description of LVNC, published in 1990, Chin et al. examined a series of eight patients with a mean age of 8.9 years, ranging from 11 months to 22.5 years in age, with isolated LVNC 5The definition of LVNC was further refined by Jenni et al. in the late 1990s to include the presence of a thin, compacted epicardal layer and a thicker, non-compacted endocardial layer. Measurements were performed in end-systole from parasternal short-axis and apical four-chamber echocardiographic views, with LVNC defined by a ratio of non-compacted to compacted tissue > 2. Additionally they stipulated that a diagnosis of LVNC requires the absence of other congenital cardiac abnormalities.6Cardiac magnetic resonance imaging (MRI) provides higher resolution evaluation of the myocardium. Based on a study of patients with established LVNC by Petersen et al., the criteria relied upon by cardiac MRI for diagnosis-include a non-compacted to compacted myocardium ratio of > 2.3 in diastole .Non-compacted LV myocardium is a remnant of embryological development. In the first gestational trimester, the heart tube loops to form into a four-chambered heart. The heart tube tissue consists of an inner endocardial cell layer and an outer myoepicardial cell mantle, as well as acellular cardiac jelly. Once the tube has looped to form a primordial ventricular, trabeculations of differentiating cardiomyocytes interspersed with deep intertrabecular recesses form in the cardiac jelly in order to provide more surface area for gas exchange for the developing tissue prior to the formation of epicardial coronary arteries. As the coronary arteries develop between the fifth and eighth week of gestation, the myocardium gradually becomes compacted into the ventricular wall. The process of compaction is generally more complete in LV tissue, leaving the mature right ventricle (RV) more trabeculated. Non-compaction results from a defect in this process.2 Inadequate blood flow to non-compacted myocardium may contribute to the development of cardiac arrhythmias. Cardiac fibrosis may interfere with the conduction system, leading to conduction delays, and reentrant circuits may develop from the border zones of fibrosis and normal myocardium. In a series of five children, aged 10 to 14 years old, Junga et al. identified evidence of non-compaction, and studied blood flow at rest with position emission tomography (PET) with [13N]-ammonia, and at stress with intravenous dipyridamole. In this group, PET images taken at rest demonstrated a 16% to 33% impairment, while PET images taken during stress demonstrated a 32% to 57% impairment, in blood flow to non-compacted myocardium, in comparison with compacted myocardium. While their patients experienced no significant arrhythmias on Holter monitoring, late potentials were seen in the resting electrocardiograms (ECGs) of three patients, and prolonged QT dispersion was identified in one patient. The authors posited that arrhythmias observed in other studies may be secondary to inadequate micro-circulation to the non-compacted myocardium.7While the mechanism of systolic dysfunction in LVNC is still not fully understood, it is hypothesized that non-compacted myocardium receives less blood flow from epicardial coronary arteries, leading to adverse remodeling over time.G4.5 gene on chromosome Xq28 are commonly seen in LVNC patients; mutations in the same gene are often associated with the onset of other cardiomyopathies, such as dilated cardiomyopathy in Barth syndrome. However, G4.5 mutations are not observed in the adult population, who demonstrate autosomal-dominant mutations more often. Patients with LVNC and LV systolic dysfunction may have mutations in alpha-dystrobrevin and in ZASP, a gene encoding Z-band protein; however, these are not observed in cases of isolated LVNC without systolic dysfunction. Furthermore, genetic mutations associated with LVNC have also been mapped to chromosomes 1, 5, and 11. Mutations in genes encoding sarcomeric proteins, which have been observed in other cardiomyopathies, are also described in cases of LVNC; these include a missense mutation in pE96K in the troponin T gene.8 LVNC has also been observed in conjunction with inherited long QT syndrome secondary to KCNH2 mutations; Ogawa et al. described one pediatric patient with an A561V mutation in the pore region, and another with a D501N mutation in the non-pore region.9 Furthermore, it has been associated with the ryanodine receptor gene (RYR2) exon 3 deletion that is described to be a causative mutation in catecholaminergic ventricular tachycardia (CPVT) and in dilated cardiomyopathy. In a series published by Ohno et al., two unrelated individual CPVT probands, each with large RYR2 exon 3 deletions, and concomitant LVNC, were identified. Among the relatives of these probands, eight of the carriers of the deletion were also diagnosed with LVNC.10Multiple genetic mutations have been implicated in the LVNC phenotype. Oechslin and Jenni describe mutations in mitochondrial, cytoskeletal Z-line and sarcomeric proteins, which are linked to autosomal-dominant, autosomal-recessive, and X-linked inheritance. In the pediatric population, mutations in the Table 2, and are also reviewed later in this article in the context of various observational studies. ECG abnormalities, however, are not the focus of this review.A variety of baseline ECG abnormalities have been reported in patients with LVNC. These are summarized in . Five of the eight patients had ventricular arrhythmias, which manifested as isolated premature ventricular contractions (PVCs) in two patients; ventricular tachycardia (VT) in two patients; and supraventricular tachycardia (SVT) with atrioventricular (AV) reentrant tachycardia that led to ventricular fibrillation (VF) in one patient. Additionally, one patient demonstrated complete heart block requiring resuscitation and permanent pacemaker placement, and two patients had resting heart rates of less than 40 bpm. On ECG, axis deviation was present in two patients, P-wave abnormality was present in three, first-degree AV block was present in two, and LV conduction defects were present in two.1In Chin et al.’s pivotal description from 1990, the series of eight patients suggested that arrhythmias could occur on a wide spectrum in LVNC patients 5A large series of LVNC patients was followed by Oechslin et al. Specifically, they described the course of 34 adults, with mean age at diagnosis 42 ± 17 years, over 44 ± 39 months. In this patient group, the following electrophysiologic abnormalities were observed: abnormal ECG ; VT ; chronic atrial fibrillation (AF) ; right bundle branch block (RBBB) , left bundle branch block (LBBB) ; and repolarization abnormality without block . Wolff–Parkinson–White (WPW) syndrome, though looked for, was not observed in any patients . During this prospective series, 12 patients (35%) died, and four underwent cardiac transplantation.11Lofiego et al. performed a retrospective analysis of 65 adult patients noted to have isolated ventricular non-compaction by TTE; these patients were followed up with for six to 193 months (a mean of 46 months). For 48 (74%) of these patients, diagnosis was based on symptoms, while in the cases of 17 (26%) patients, diagnosis was not symptom-based, but rather based on family referral, ECG abnormalities, elevated biomarkers, and the presence of heart murmur. In the group of patients with a symptom-based diagnosis, sustained VT occurred in four (8%), syncope in three (6%), permanent AF in six (13%), and sudden death in three (6%) patients over the course of follow-up. Interestingly, none of these arrhythmias were found in patients in the group without symptoms. Additionally, over the course of follow-up, the symptom-based group had 15 (31%) instances of cardiovascular-related deaths or heart transplantation, as compared with zero (0%) in the group without symptoms. In univariate and multivariate analysis, sustained VT was a significant predictor of death or transplantation, while permanent AF and syncope were not significantly associated with these outcomes.12In a previous systematic review, Bhatia et al. compiled data from five cohorts of patients with LVNC to create a sample size of 241 patients. They cited data from five studies, in which Holter monitoring was performed symptom-driven in one study and routinely in four. From the data pooled from these studies, AF was found in 23 patients ; non-sustained VT (NSVT) in 36 patients , sustained VT in eight patients ; and unspecified VT in four patients (n = 4). The authors further reported that 26 patients (11%) had an implantable cardioverter-defibrillator (ICD) placed for VT ; presyncope with inducible VT on electrophysiology (EP) study ; and primary prevention of sudden cardiac death . Additionally, they noted that one patient died of refractory VT, that two survived appropriate ICD discharges, and that two were inappropriately shocked for atrial dysrhythmias.13While this article has primarily focused on reviewing arrhythmias in adult patients in LVNC, it is important to note that cardiac arrhythmias can manifest in ILNC patients during childhood, with slightly different phenotypes. In a series of pediatric patients with LVNC, the incidence of arrhythmia was high, though the proportion of ventricular arrhythmias was lower. Ichida et al. conducted a nationwide survey of 150 Japanese hospitals, identifying 27 patients with confirmed LVNC by echocardiography for inclusion in the study, with ages ranging from one week to 15 years at presentation. Follow-up for these patients extended for as long as 17 years after presentation. Twenty-two (88%) of these patients had baseline abnormalities on ECG, including ST depression, T-wave flattening or negative T-waves in the inferior and lateral precordial leads, and RBBB, in addition to QRS axis deviation and evidence of chamber enlargement. The authors noted that there were fewer instances of LBBB than was seen in adults with LVNC. Three patients had WPW syndrome, and a fourth had a concealed accessory pathway involved in SVT. Over the course of follow-up, 13 (48%) patients had significant arrhythmias, including paroxysmal SVT ; AF ; PVCs ; second-degree AV block ; and complete heart block . This cohort demonstrated no sustained VT or NSVT.1 The cohort followed by Ichida et al. also included patients with bradyarrhythmias. Of the 27 patients with LVNC included in the study, two developed second-degree AV block, and one had complete heart block.10 In addition to these, two case reports have described bradyarrhythmias.Bradyarrhythmias from sinus node dysfunction to progressive degrees of AV delay and block have been noted in LVNC patients. Chin et al. reported two patients with significant sinus bradycardia, two patients with first-degree AV block, and one patient with complete heart block in their series.14A case of a patient presenting with complete AV block as a first manifestation of LVNC non-compaction was described by Nascimento et al. This patient had dyspnea on exertion, as well as prescyncope, which progressed to four episodes of syncope with Holter monitoring, revealing sinus bradycardia with AV delay, second-degree Mobitz II AV block, and episodes of complete AV block, requiring placement of a permanent pacemaker. Her TTE confirmed LVNC by the presence of numerous and prominent trabeculations.15Jackson et al. similarly described the case of a patient diagnosed with non-compaction after the occurrence of complete atrioventricular block with syncope. After non-compaction was diagnosed on TTE, this patient had a dual-chamber ICD implanted, and went on to develop ventricular tachycardia.8 Notably, SVTs described in this patient population include AF and atrial tachycardia (AT).SVT tends to be more prevalent in children with LVNC, though AF is reasonably common in adult patients, as reported in the Chin et al., Oechslin et al., and Lofiego et al. series.16In a case report by Kato et al., a 19-year-old man with a first presentation of AT that occurred during childhood suppressed with β-blockers re-presented with presyncope associated with episodes of rapid AF followed by VT, which was demonstrated on Holter monitoring. Echocardiogram demonstrated prominent trabeculations and intertrabecular recesses in the LV, together with mild LV dilation and mildly reduced LV fractional shortening, consistent with non-compaction. During EP study, AF and AT were easily triggered by isoproterenol infusion, and VT followed these rhythms, requiring multiple shocks. The pulmonary veins were isolated, and subsequently neither AF nor VT was inducible. The authors did not comment on whether this patient received an ICD. He had no further SVT episodes during a follow-up period of three years.17Alihangolu et al. described a 25-year-old woman with a history of palpitations, sweating and shortness of breath for two months who was found to have non-compaction with an LV ejection fraction (EF) of 32%. The patient’s presenting rhythm was AF with rapid ventricular response.Ventricular arrhythmias have been described more frequently in adults with LVNC. Monomorphic VT, polymorphic VT, bidirectional VT, and VF have all been cited several times, and together raise concerns regarding the higher risk of sudden cardiac death in this patient population.Monomorphic VT. In Oechslin’s series of 34 patients with LVNC, ventricular tachycardias were demonstrated in 14 patients (41%), with NSVT seen in 11 and sustained VT seen in three. Though one patient died within an hour of VT onset, ICDs were successfully implanted in four patients, specifically for sustained VT in two, and for presyncope with inducible VT by EP study in two. One patient with an ICD died from refractory VT.518Fazio et al. followed a series of 238 consecutive patients with LVNC from the Italian Society of Echocardiography registry between May 2005 and September 2006, using serial monitoring. Patients were followed for a mean period of 4.13 years , during which time, clinical evaluation, ECGs and 24-hour Holter monitoring were performed every six months. The investigators observed that 11 patients (4.3%) in this cohort had VT on Holter, with sustained VT noted in two patients. Patients with VT were noted to have a mean LV EF of 43.72%, with a range of 16% to 60%. One patient was a three-year-old male child with fascicular VT, which was ablated successfully. Over the course of the follow-up, an ICD was implanted in one patient, and there were no deaths. Patients with observed VT were treated with β-blockers.19 In a separate case report, Alihanoglu et al. described a 25-year-old woman with AF at the time of LVNC diagnosis who had sustained VT induced during her EP study, and who required amiodarone for cardioversion and hemodynamic stabilization. Given her reduced LV EF, she was optimized on goal-directed medical therapy; an ICD was implanted prior to discharge.17In a case series of 25 patients with a personal history of VT, along with a family history of sudden cardiac death, in the absence of angiographically significant coronary artery disease, cardiac MRI was performed for further evaluation. In this series, MRI revealed non-compaction in three patients.20Non-sustained monomorphic VT arising from the LV has been described. Vijayvergiya et al. detailed the case of a 32-year-old man who was found to have asymptomatic salvos of NSVT with RBBB morphology. TTE at the time of diagnosis showed non-compaction with an LV EF of 30%. The patient’s tachycardia was successfully suppressed with amiodarone, but ICD implantation was deferred due to financial constraints.21 This case is similar to another case reported by Gonzalez et al., where a 19-year-old patient had LVNC diagnosed by cardiac MRI and who developed an epicardial VT from the RV. A 12-lead ECG of her VT is displayed in Figure 2, and voltage mapping performed to guide her ablation is shown in Figure 3.22 In both of these cases, as well as in the next, it is noted that RV non-compaction (RVNC) is less frequently described; normal RV myocardium can be highly trabeculated, which may decrease identification. Additionally, Osmonov et al. also described a patient with VT originating from the RVOT in conjunction with LVNC. This patient was a 16-year-old male who was noted to have frequent PVCs with left bundle branch (LBB) morphology, inferior axis, and precordial transition at V4. His TTE showed an LV EF of 29%, with non-compaction of the apical and lateral LV walls. During EP study, his VT was pace-mapped to the anteroseptal RVOT, and was successfully ablated using radiofrequency (RF) energy. Two months after the ablation, non-compaction persisted, but his LV EF had improved to 53%; there were no PVCs observed on 24-hour Holter monitoring.23VT in a structurally normal RV has been reported in association with a non-compacted LV. Honarbaksh et al. described the case report of a 67-year-old man with established isolated LVNC. He also had a history of RV outflow tract (RVOT) ventricular extrasystoles status post-ablation in the past, but had developed new ventricular ectopy and runs of NSVT from the basal RV localized to the inferolateral tricuspid annulus. By cardiac MRI, the RV free wall displayed no evidence of non-compaction. It is possible that the occurrence of monomorphic VT from the RV is unrelated to this patient’s underlying non-compaction. However, the authors stipulate that the two processes may have been related—namely, that MRI may not have been sensitive enough to detect RV trabeculations, or that the VT may have resulted from an accessory pathway that regressed.24In a short case report, Santoro et al. described a patient with LV non-compaction afflicted by monomorphic VT of multiple morphologies. This patient was a 74-year-old man who presented with palpitations, and who was found to have monomorphic VT with LBB morphology and right inferior axis. His TTE showed his LV EF was depressed to 40%, with non-compaction of both the LV and RV. No EP study was performed, but the patient was discharged with an ICD and on amiodarone.25Ablation of VT in LVNC has been described in several patients as a treatment for VT and PVCs. Lim et al. presented a patient who underwent successful endocardial and epicardial mapping, as well as RF ablation, for monomorphic left VT. A 52-year-old man with a prior history of presyncope and palpitations was admitted with palpitations and dizziness, and was found to have VT with a RBBB, right inferior axis. Echocardiogram demonstrated LVNC with an LV EF of 30%. In the EP laboratory, VT was easily inducible, and was mapped to the anterolateral LV, with possible epicardial origin. Therefore, simultaneous endocardial and epicardial mapping was done, with radiofrequency ablation performed at the site of earliest activation on the anterolateral LV epicardium. Ablation was successful, and the patient remained free of VT during the following eight months.15 described a case of refractory VT in a patient with non-compaction that went on to receive catheter ablation. Their patient was an 18-year-old male who was diagnosed four years prior with mild LVNC involving the free wall and distal septum and associated with an LV EF of 45% to 55%; he had undergone dual-chamber ICD implantation at the time of diagnosis, due to syncope with noted complete heart block, described previously. He went on to experience symptomatic sustained and non-sustained monomorphic and polymorphic VT requiring multiple shocks and antiarrhythmics over the following four years. Owing to refractory VT, he underwent substrate-based electroanatomic mapping of three distinct VTs in the left ventricle, and ablation of the best pace-matches as well as the sites with fractionated and late potentials with 46 RF lesions. Over the following 12 months, the patient experienced only a single four-beat run of NSVT.12Jackson et al.26Paperella et al. allude to nuances in the evaluation of sudden cardiac death (SCD) risk for patients with non-compaction in a case report of a 59-year-old man admitted with palpitations who was found to have a wide-complex tachycardia with right bundle branch morphology, left superior axis, consistent with a VT from the LV, which was suspected to be originating from the posterior papillary muscle. After TTE showed a dilated LV with reduced EF < 25% and hypertrabeculated endocardium in the LV apex, with non-compacted to compacted myocardial ratio consistent with non-compaction, the patient underwent an EP study, during which no sustained SVT or VT was inducible; furthermore, pace mapping of the LV demonstrated no match to the clinical VT, and voltage mapping of the LV revealed no abnormalities. No ablation was performed, but an ICD was implanted at that time because of the presence of a past medical history of syncope in addition to the VT documented on presentation.27Recently, Muser et al. identified nine patients with known LVNC amongst a cohort of 1,816 patients with VT or frequent PVCs who underwent RF ablation. Seven of the nine patients in the series had frequent PVCs, and two had VT storm. It was noted that focal PVCs tended to arise from the LV basal-septal regions and papillary muscles, while VT involved mid-apical LV segments, matching the non-compacted myocardial segments. Catheter ablation was successful in eight patients. The VT patients had no recurrence at four and seven months of follow-up, and those patients with PVCs displayed a significant reduction in PVC burden.Bidirectional VT. Two patients have been described as having bidirectional VT in the LVNC literature. In a short imaging report, Arias et al. detailed the case of a 29-year-old woman with LVNC evidence from cardiac MRI who developed bidirectional VT. She initially presented with a wide-complex tachycardia consistent with a left bundle, right inferior axis with transition at V5; this was terminated with cardioversion. During invasive EP study, a single extra stimulus at the RV apex initiated bidirectional VT, with one morphology identical to the presenting rhythm, and the other a left bundle, right superior axis with transition at V6.2829Fiala et al. described a case of bidirectional VT from a deep septal focus. In this case, a 17-year-old male who had been diagnosed with biventricular non-compaction four years prior with reduced LV EF and symptoms of heart failure experienced a bout of VT that was unable to be controlled with antiarrhythmic medications. He underwent electroanatomic mapping and ablation of his clinical LBBB morphology VT over the RV septum adjacent to the insertion of trabecular septomarginalis, but he subsequently developed a second RBBB morphology VT. Repeat mapping and ablation were performed from the LV over the septum, but this was limited by steam pops. Repeat ablation was performed by the RV septal side with successful suppression of all VT on β-blocker therapy alone.Polymorphic VT. Cases of polymorphic VT in LVNC have been reported, possibly in conjunction with underlying genetic channelopathies.30In a short communication, Seres et al. presented a case of polymorphic VT in a 57-year-old woman with a family history of SCD, with a presenting symptom of syncope. Upon evaluation, she was found to have a LV EF of 46%, with evidence of non-compaction by prominent trabeculations and deep intertrabecular recesses in her anterior and lateral apical wall segments on TTE, and a prominent trabecular zone and deep intertrabecular recesses in the anterior wall by left ventriculography. Telemetry showed multiple episodes of polymorphic VT. Invasive EP study revealed a prolonged HV interval at 62 ms; programmed ventricular stimulation with up to three extrastimuli from the RV apex failed to induce ventricular arrhythmias. Given that polymorphic VT persisted despite the use of β-blockers, and that the patient at baseline had prolonged HV conduction, a dual-chamber ICD was implanted. There was no evidence of an inherited long QT syndrome being present on ECG screening of the patient’s living immediate relatives.KCNH2 mutation was described in two case reports by Ogawa et al. The first discusses a one-day-old male who, 13 hours after birth, developed tachypnea, tachycardia, hypotension, and cyanosis accompanied by metabolic acidosis and hypocalcemia; his ECG showed LBBB with prolonged QT. Following calcium repletion, he developed polymorphic VT, which was treated with lidocaine, cardioversion, and magnesium. Subsequent ECGs and Holter monitoring showed both narrow QRS morphologies and LBBB intermittently. An echocardiogram demonstrated hypertrophic trabeculations, mostly in the apical LV endocardium. His genetic analysis was significant for KCNH2 (LQT2) missense mutation A561V. The second case involved a five-year-old male with a seizure disorder who was found to have prolonged QT at 590 msec. Holter monitoring demonstrated T-wave alternans and Torsades de pointes. An echocardiogram revealed prominent trabeculations in the apical, lateral and inferior LV, with preserved EF of 74%. The patient’s genetic analysis was also significant for a mutation in KCNH2 with D501N. The authors raise the concern regarding the higher risk of SCD in such patients, and recommend the implantation of an ICD.31Polymorphic VT in the context of prolonged QT due to RYR2 gene encoding the ryanodine receptor. This patient suffered multiple expertional syncopal episodes as a child and adolescent, with one episode occurring with documented AF. When her AF was recognized after syncope at age 16, a TTE showed new trabeculations in the LV apical and posterior free walls. She subsequently experienced an episode of VF cardiac arrest during exertion one year later, and was found to have LVNC. After that event, an ICD was implanted. Four more instances of VF cardiac arrests occurred, and the patient was treated with multiple antiarrhythmic agents, followed by a bilateral sympathectomy. On comprehensive genetic testing, this patient was found to have deletion of the RYR2 gene, which has been reported in other cases of CPVT. This patient’s course is significant, as her time course of worsening arrhythmias coincided with the development of LVNC, which was not present on TTEs at the times of her initial syncopal episodes. Furthermore, it raises the question of whether her CPVT and LVNC may both be associated with her genetic mutation.32Campbell et al. described an interesting case of CPVT occurring in a patient who developed LVNC, and who was found to have deletion of exon 3 of the VF. VF in the context of LVNC has been reported in three children and one adult. Although ventricular arrhythmias are rarer in pediatric patients, Celiker et al. described the clinical course of a six-year-old female with recurrent syncope whose baseline ECG showed biphasic T-wave inferiorly and laterally. She was found to have evidence of non-compaction on TTE, with a preserved EF of 65%. After presentation with VF, she had recurrence of VF that required amiodarone and several defibrillations. She underwent ICD implantation, and was discharged on amiodarone and propranolol. Three episodes of VF were treated by her ICD in the following 16 months.3334Additionally, Ergul et al. documented the case report of a four-year-old male with recurrent syncope in the prior year who was admitted after aborted SCD; his ECG showed non-specific ST-T changes, and TTE revealed non-compaction. During EP study, polymorphic VT was induced by programmed ventricular stimulation, and an epicardial ICD was implanted. Five months after discharge, he experienced VF, for which he received an appropriate shock.35Cohen and Prahlow describe SCD in a 14-year-old African-American girl who was found to have LVNC. She had a history of “episodic tachycardia,” which had been treated with ablation eight years prior. With cardiac arrest, she had seizure-like activity, and was noted to be asystolic on arrival, with multiple subsequent defibrillations for VT and VF needed during resuscitation over the course of 5.5 hours. Autopsy revealed biventricular dilatation with LV apical non-compaction and subtle RVNC; it does not appear that the diagnosis of non-compaction was known prior to autopsy.36Sato et al. described an instance of cardiac arrest because of VF in a 57-year-old previously healthy man who was found to have flattened T-waves in the lateral precordial leads on ECG and an LV EF of 58%; cardiac MRI showed non-compacted myocardium in the lateral and apical walls. Subsequent EP study was notable for the presence of late diastolic potential, and programmed ventricular stimulation from the RV apex with triple extrastimuli induced VF. After implantation on an ICD, the patient had one episode of VF that was treated in the subsequent eight weeks.37 Several case reports and series have detailed experiences in using invasive EP studies to risk stratify patients.Based on these reports of ventricular arrhythmias, it can be inferred that patients with LVNC are at a higher risk for SCD. Ritter et al. reported a 47% incidence of ventricular arrhythmias in non-compaction, with these arrhythmias accounting for half of the deaths in this patient population; furthermore, it seems that fatal ventricular arrhythmias occur more frequently in those with decreased LV EF.38In order to identify patients at risk for ventricular arrhythmias, Steffel et al. studied the prognostic significance of findings during EP study. A retrospective analysis of EP study findings and clinical follow-up for 24 patients with LVNC at two Swiss centers was performed. During EP study, with ventricular extrastimuli and isoproterenol infusion, ventricular arrhythmias were inducible in nine patients (38%); two had sustained monomorphic VT, two had sustained polymorphic VT or VF, and two had non-sustained polymorphic VT. Of the nine patients, seven underwent ICD implantation, and three of these patients went on to experience ventricular arrhythmias over a follow-up period of 61 months; all of these instances of tachyarrhythmia were treated with ATP or shock. Additionally, supraventricular arrhythmias were induced in seven patients (29%), including AF, AV reentrant tachycardia, AV nodal reentrant tachycardia, and atrial flutter. Three patients were noted to have abnormal AV conduction with two having complete heart block (8%) and one having prolonged AV delay.39Additionally, investigators have also followed the outcomes of LVNC patients following ICD implantation to assess the need for therapy: in a retrospective analysis of 12 patients with LVNC who had undergone ICD implantation, Kobza et al. evaluated the rationale for implantation and observed the incidence of appropriate ICD shocks. In two Swiss hospitals from September 1997 to November 2009, 105 patients were diagnosed with LVNC. Based on a patient history of symptomatic arrhythmias or severely reduced LV EF on admission, either secondary or primary prevention ICDs were implanted in 12 patients . EP study to evaluate for inducible ventricular tachyar-rhythmias was performed in seven patients; ventricular tachyarrhythmias were induced in six patients (86%), which were sustained in three (43%) and non-sustained in three (43%). Single-chamber ICDs were implanted in six patients (50%), dual-chamber ICDs were implanted in four (33%), and biventricular ICDs were implanted in two (16%). During a follow-up period of 1.1 to 98.4 months (median of 36 months), five patients (42%) experienced appropriate ICD therapy ; all patients with sustained VT on EP study experienced appropriate ICD therapy. Four of the eight patients (50%) implanted with ICDs for secondary prevention and one of the four patients (25%) implanted with an ICD for primary prevention experienced appropriate ICD therapies. A high proportion of patients with ICDs  experienced supraventricular tachyar-rhythmias during follow-up. Three inappropriate shocks occurred for sinus tachycardia, AF, and T-wave over-sensing, respectively.40This series of patients was expanded to 30 patients, with the inclusion of cardiac resynchronization therapy (CRT) in a subsequent report from Kobza et al. In this larger group, primary prevention ICDs were implanted in 18 patients, and secondary prevention ICDs were implanted in 12. During the follow-up period of 40 ± 34 months, 11 patients  presented with appropriate ICD therapies. Appropriate therapies occurred after a mean follow-up period of 21 ± 16 months. Furthermore, functional New York Heart Association class improved in the six patients who received CRT as well. The authors concluded that implantation of ICDs in LVNC patients for primary or secondary prevention was appropriate, although the clinical indicators for appropriate ICD therapy were unable to be established.Although LVNC is a rare cardiomyopathy, arrhythmic manifestations of the disease are often significant, and can lead to mortality. Cardiac arrhythmias most likely result from the development of fibrosis in non-compacted myocardium, with the occurrence of the development of conduction delays and reentrant circuits at the border zones of fibrosis and normal myocardium. Arrhythmic manifestations can range from conduction disease to SVT and ventricular arrhythmias. Due to the development of ventricular arrhythmias, these patients are at higher risk for SCD. EP study or the implantation of an ICD should be considered for these patients, especially if they demonstrate signs of any ventricular arrhythmias or a reduced LV EF.


Multivariable analysis revealed that LVEDVI was the independent predictor for MACE, while myocardial mass was the independent predictor for 3- and 12-month readmission. Myocardial TG content (lipid resonances δ 1.6 ppm) was significantly associated with readmission in patients with ischemic heart disease. Conclusions: LVEDVI and myocardial mass are potential imaging biomarkers that independently predict MACE and readmission, respectively, in patients discharged after hospitalization for acute HF. Myocardial TG predicts readmission in patients with a history of ischemic heart disease.Background: This prospective study was designed to investigate whether myocardial triglyceride (TG) content from proton magnetic resonance spectroscopy (MRS) and left ventricular (LV) function parameters from cardiovascular magnetic resonance imaging (CMR) can serve as imaging biomarkers in predicting future major cardiovascular adverse events (MACE) and readmission in patients who had been hospitalized for acute heart failure (HF). Methods: Patients who were discharged after hospitalization for acute HF were prospectively enrolled. On a 3.0 T MR scanner, myocardial TG contents were measured using MRS, and LV parameters (function and mass) were evaluated using cine. The occurrence of MACE and the HF-related readmission served as the endpoints. Independent predictors were identified using univariate and multivariable Cox proportional hazard regression analyses. Results: A total of 133 patients  were enrolled. The mean duration of follow-up in surviving patients was 775 days. Baseline LV functional parameters—including ejection fraction, LV end-diastolic volume, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume ( Heart failure (HF) is a complex clinical syndrome that results from a variety of conditions preventing the left ventricle (LV) from supporting physiological circulation . Patient1H-MRS) has been used to obtain in vivo quantitative measures of myocardial TG content in patients with CV disorders [1H-MRS and LV function parameters from CMR may help predict the occurrence of future MACE and readmission in patients who have been hospitalized for acute HF.Cardiomyocytes primarily depend on the oxidation of fatty acids as their source of energy . Becauseisorders ,11,12. Wisorders . Furtherisorders ,15,16. W1H-MRS (primary aim) and LV function parameters from CMR (secondary aim) can serve as imaging biomarkers in predicting future MACE and readmission in patients who have been hospitalized for acute HF.This prospective study was designed to investigate whether myocardial TG content from Ethical approval was granted by the Institutional Review Board of the Keelung Chang Gung Memorial Hospital (IRB 102-2772A3). The study is reported in accordance with the STROBE  statement and has been registered at ClinicalTrials.gov (Identifier: NCT02378402) on 21 February 2015. All patients provided their written informed consent.Between March 2014 and June 2016, we prospectively screened 200 patients and enrolled a total of 147 patients who were hospitalized with acute HF at a tertiary referral hospital with a dedicated HF center . Patients were scanned whose medical condition had become stable after treatment, specifically when they (1) had an oral medication regimen stable for at least 24 h; (2) had no intravenous vasodilator or inotropic agents for at least 24 h; and (3) were ambulatory before discharge to assess functional capacity. Patients aged between 20 and 70 years with acute HF, with initial HF stage C, classified according to the American College of Cardiology (ACC) and the American Heart Association (AHA) HF classification system . In this1H MRS voxels to a 2 × 2 × 1 cm3 spectroscopic volume within the interventricular septum during the end-systolic phase. The MRS acquisition parameters were as follows: Nominal TR (repetition time)/TE (echo time), 550 ms/33 ms; 64 averages; window size, 1024 points; bandwidth, 2000 Hz [Clinical MRS was acquired before contrast administration using the same settings and anatomical localizations as previously reported . In brie 2000 Hz ,19,20,21 2000 Hz .Patients were required to fast overnight before undergoing CMR examinations on a 3.0-Tesla Siemens Skyra MR scanner . No pre-medications were used. The scanner was equipped with an 18-channel phased-array receiver body coil and operated on a VD13 platform. Steady-state free precession (SSFP) cine imaging was used to produce images with both short-axis (contiguous 8 mm slice thickness) and standard long-axis views . Late gadolinium enhancement (LGE) at 10 min after gadolinium injection in the short-axis (9 to 13 images covering the entire LV), 2-chamber, and 4-chamber planes. The following settings were employed: Echo time, 1.2 ms; repetition time, 3.4 ms; field of view, 34−40 cm; matrix, 256 × 256.Left ventricular ejection fraction (LVEF) was measured on short-axis cine LV images with post-processing software  on a separate workstation. LV endocardial and epicardial borders were manually drawn at end-diastole and end-systole on short-axis cine images and LVEF and end-diastolic LV mass from each slice were measured accordingly. Papillary muscles were not included in the LV mass. Left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were calculated using the same methodology. The left ventricular end-diastolic volume index (LVEDVI) was determined by dividing the LVEDV by the body surface area (BSA). The LV global function index (LVGFI) was calculated with the following formula:http://s-provencher.com/pages/lcmodel.shtml) was used for the quantification of TG by fitting the time-domain 1H-MRS spectra (2)n–CH3) peak δ 0.9 ppm, methylene (–(CH2)n–) peaked at 1.3 ppm, beta-carboxyl (–CO-CH2-CH2–) at 1.6 ppm, alpha-allylic (–CH2–CH=CH–CH2–) peaked at 2.02 ppm (denote by Lip2.1), alpha-carboxyl (–CO-CH2-CH2–) peaked at 2.24 ppm (denote by Lip2.3), diacyl (–CH=CH–CH2–CH=CH–) peaked at 2.75 ppm (denote by Lip2.8), olefinic (–CH=CH–) at 5.29 ppm (denote by Lip5.3) were fitted. Water-suppressed spectra were used to quantify the total myocardial TG resonance and its—including FA  and UFA , i.e., the ratio of the metabolite resonance area to the unsuppressed water resonance area. Water resonance (~δ 4.7 ppm) without water suppression was also determined for normalization. Cramer-Rao lower bound (CRLB) of TG provided by the LCModel was served as a goodness-of-fit, and used for the evaluation of the spectra quality.LCModel 6.2 software package  and chi-square test, respectively. Continuous variables were determined by the recursive partitioning method to obtain the optimal cut-off values. Independent predictors of MACE and readmission rates were identified using univariate and multivariable Cox proportional hazard regression analyses. A Bonferroni posthoc correction was conducted to reduce Type I Error by dividing the original α-value by the number of analyses on the dependent variable. Data correlation was evaluated based on the Spearman rank test. Data analyses were performed using the following software: SPSS , MedCalc , and R .Univariate and stepwise multivariable regression analyses  were used to assess CMR parameters. A complete-case analysis was implemented (missing data were not excluded). Survival curves were plotted with the Kaplan-Meier method (log-rank test). Two-group comparisons of continuous and categorical variables were performed with the Student’s n = 71) than reduced EF <55% (n = 62). MACE was observed in 39 cases (29.3%). The MACE with their distribution being as follows: HF-related readmission , re-hospitalization for acute myocardial infarction , unstable angina , cardiac arrest , and stroke . There were no cases of cardiac death. The baseline clinical characteristics of the study participants are summarized in n = 2), left anterior descending (n = 36), left circumflex (n = 26), and right coronary artery (n = 23), verified by the presence of a myocardial scar on LGE. The remaining 83 patients had no history of ischemic heart disease and had no myocardial scar on LGE.A total of 133 consecutive patients  entered the final analysis, with the mean follow-up time for surviving patients being 775 days. p < 0.0001). The results of univariate Cox regression analysis for MACE and HF-related readmission are shown in 2) had a lower probability for MACE than those with high LVEDVI .All of the CMR parameters  were reciprocally correlated with one another (p < 0.0001). In non-ischemic patients, Kaplan-Meier survival analysis (p < 0.0001). Myocardial TG content was not associated with MACE or HF-related readmission in non-ischemic patients. The levels of lipid resonances δ 1.6 ppm inversely correlated with the myocardial mass  and LV global volume  in non-ischemic patients. No correlations between the myocardial TG content and CMR functional parameters were found in the ischemic patient group.We found that baseline myocardial TG content—FA/UFA ratio—was significantly associated with the MACE, whilst the level of lipid resonances δ 1.6 ppm was significantly associated with HF-related readmission for those patients with ischemic heart disease. Kaplan-Meier survival analysis  demonstranalysis  demonstr1H-MRS) and LV function parameters (measured on CMR) in the prediction of MACE and readmission in patients hospitalized for acute HF. Our main results can be summarized as follows. First, an increased LVEDVI was identified as an independent predictor of reduced MACE-free survival. Second, myocardial mass was independently associated with 3- and 12-month readmission rates. Finally, we found myocardial TG content—FA/UFA ratio—was significantly associated with MACE, whilst the level of lipid resonances δ 1.6 ppm was significantly associated with HF-related readmission for patients with ischemic heart disease. Taken together, these data indicate that assessment of LV function on CMR may improve the risk stratification of patients who have been hospitalized for acute HF. 1H-MRS assessment might be reserved for patients with a history of ischemic heart disease.This study was designed to simultaneously assess the prognostic significance of myocardial TG content (assessed by 1H-MRS might be supplementary to the diastolic dysfunction to improve the stratification for patients with ischemic heart disease.In patients with HF, diastolic wall strain has been reported as an independent predictor of MACE , and theReadmissions are frequent in patients with acute HF and served as a secondary outcome measure in the current study. A previous report demonstrated that diabetes mellitus, hyperlipidemia, CAD, length of stay at the index admission, and prescription of beta-blockers were significant predictors of readmission rates . The 30-2 resonance δ 1.3 ppm. The sum of the signal intensities δ 0.9, 1.3 and 1.6 ppm would have been more reliably extracted from an in vivo cardiac 1H-MRS. Nonetheless, the quantitative analysis was carried out using well-established LC Model software to enhance the generalizability of the current study. Third, longitudinal 3-T CMR and 1H-MRS examinations were not performed and changes in LVEDVI and/or myocardial TG content were not investigated over time. A validation cohort for our findings would help to elucidate the clinical value of such imaging biomarkers, however, it was outside of the pre-specified analysis for this study.Our data should be interpreted in the context of some limitations. First, the single-center of our study may bring into question its generalizability, as the study population was highly selected for those with medical conditions becoming stable and ready to discharge. The number of HF-related readmissions might be too small for meaningful multivariable analyses. However, it is noteworthy that patients were recruited regardless of the underlying cause of HF. The data should be interpreted carefully because pathophysiologically diverse endpoints were included in this study. Second, the resonance δ 1.6 ppm sometimes overlaps with the main CHOur results indicate that LVEDVI and myocardial mass are potential imaging biomarkers that independently predict MACE and readmission, respectively, in patients discharged after hospitalization for acute HF. Myocardial TG predicts readmission in patients with a history of ischemic heart disease. Further studies are needed to determine whether LVEDVI and myocardial mass, as well as myocardial TG, may serve as therapeutic targets to improve prognoses in targeted patient populations.


Right heart failure (RHF) after left ventricular assist device (LVAD) implantation is common and associated with worse outcome. Prediction of RHF remains challenging. Our study aims to assess predictors of RHF focusing on clinical manifestations.We retrospectively analyzed clinical, echocardiographic and hemodynamic parameters of 112 patients undergoing LVAD implantation. Pre-operative, early  and late postoperative RHF  were assessed.p < 0.001), higher pulmonary vascular resistance (p = 0.046) and CVP/PAWP quotient (p = 0.011), higher bilirubin (p = 0.038) and creatinine (p = 0.013). LRHF was associated with creatinine (p = 0.006), urea (p = 0.012) and load adaption index (p = 0.007). Binary logistic regression models identified no single risk factors. Comparing the predictive value of regression models with a model of three clinical findings  did not reveal differences in RHF.In the total study population , early RHF was frequent (47% on day 7 and 30% on day 14). Prevalence of late RHF and death from RHF was high after 3, 6 and 12 months . Pre-existing RHF was only associated with early RHF and persistent, but not for new onset late RHF. Early RHF was associated with lower INTERMACS level (RHF before LVAD implantation enhances the risk of early RHF and persistent late RHF, but not for new onset late RHF, supporting the hypothesis of differences in the etiology. Echocardiographic or hemodynamic parameters did not show a predictive value for new onset late RHF. Similar predictive value of clinical findings and statistic models of risk factors suggest that a clinical evaluation is equally matched to predict RHF. Due to the lack of heart donors, mechanical assist device support has become an important alternative to heart transplantation in care among patients with advanced heart failure. Despite advances in technology and greater familiarity with patient management, overall survival remains essentially unchanged since 2013 at 80% after 1 year and 70% after 2 years [Right heart failure (RHF) is one of the most common complications after continuous flow left ventricular assist device (LVAD) implantation with high impact on outcome , 3. TherMany attempts were done to predict RHF after LVAD implantation. These approaches include echocardiographic parameters like TAPSE. Besides, parameters derived from right heart catheterization like central venous pressure (CVP) and laboratory parameters like bilirubin or creatinine were used. All these attempts failed to predict RHF accurately , 5.TR) [In addition, combinations of parameters like load adaptation index of the right ventricle (LAI) and tricuspid valve velocity time integral (VTITR)  or complTR) , 8 predoTR)  of obserbefore LVAD implantation, we aimed to show their impact on early and late RHF after LVAD implantation. We refer to and focus on the INTERMACS definition of RHF [By analyzing epidemiological aspects of RHF n of RHF  that is n = 3). Furthermore, we excluded patients who additionally received a right ventricular assist device (RVAD) for permanent biventricular support  and patients with the need for chronic hemodialysis before LVAD implantation (n = 1). Two cases with lost-to-follow up < 14 days after surgery were excluded.The screening population consisted of all subjects ≥18 years of age undergoing elective or emergency LVAD implantations between January 2009 and May 2017 at University Heart Center Hamburg. A total of 132 subjects met the screening criteria. We excluded all patients that did not receive a continuous flow device of the HVAD™ type from Heartware® (Criteria of RHF were adapted from INTERMACS definition  requirin1. Documentation of elevated CVP by direct measurement (CVP or RAP > 16 mmHg) or dilated inferior vena cava with absence of inspiratory variation or elevated jugular venous distension.> 2 either new or unresolved), presence of ascites or palpable hepatomegaly , or laboratory evidence of hepatic  or renal dysfunction (creatinine > 2.0 mg/dl).2. Manifestations of elevated central venous pressure characterized by peripheral edema  and were compared by Student T-test.p < 0.1 in at least one analysis. Backward selection was performed with p < 0.3. Model fit was evaluated by Hosmer Lemeshow Test. Nagelkerke‘s R2 was reported. Kaplan-Meier curves were used to analyze survival and were compared by log-rank test.Risk factors for early RHF and late RHF were analyzed using a multiple logistic regression model. Covariates were selected by univariate factor analyses. A variable was included if A 5% level of significance (two-sided) was used for any statistical test. Descriptive, interferential and survival statistics were performed by IBM SPSS, Version 24 for Windows. Missing data were imputed by “missForest” package for R  to increPatients had a mean age of 55 years (SD 13), 12.5% were female. Pre-operative RHF was present in 72 cases (64.3%). Two thirds of devices were implanted as bridge to transplant (BTT). In half of the patients, dilated cardiomyopathy was the underlying disease, while 34.8% of patients suffered from ischemic cardiomyopathy. Almost all patients had a left ventricular ejection fraction (EF) < 30%. Patients with baseline EF > 30% were treated within the context of fatal heart failure after cardiac surgery. Apart from highly reduced EF, moderate or severe mitral valve regurgitation (46.5%) and tricuspid valve regurgitation (40.2%) were frequent.p = 0.007), a higher CVP/PAWP quotient (p = 0.026) and CVP (p = 0.032) than patients without pre-operative RHF. They had an infection more frequently, lower hemoglobin (p = 0.003) and a lower INTERMACS level (p < 0.001). There were no differences in parameters of the echocardiographic assessment, in the underlying disease and the indication for LVAD implantation  was reached 30 days after surgery. Afterwards the prevalence increased and the share of patients who died due to RHF grew. Only half of the patients with late RHF were permanently affected by RHF. The other half had new onset RHF. Within the first 6 months, RHF was the most common cause of death (31.4% of deaths). In contrast, only 5% of deaths were classified as caused by RHF afterwards while sepsis and major bleeding became more frequent causes of death  and persistent RHF , but not for new onset LRHF . The same pattern was found for the combined outcomes for early RHF or death from RHF  and late RHF or death from RHF  between patients with and without pre-operative RHF. Nevertheless, pre-operative RHF was associated with a lower survival rate (p = 0.020) up to 14 days after surgery. Afterwards, the impact of pre-operative RHF diminished.Pre-operative RHF was a strong risk factor for ERHF  than of patients without early RHF. Differences between the survival curves developed within the first 2 weeks and remained stable. Survival of patients with ongoing early RHF, recurrent or new onset late RHF was worse (p < 0.001) compared to patients without post-operative RHF or RHF only in the early post-operative period , classified into a lower INTERMACS level (p < 0.001), had a higher CVP/PAWP quotient (p = 0.011), lower load adaption index (p = 0.019) and higher urea (p = 0.010) and creatinine (p = 0.013). Regarding late RHF, associations were obvious for creatinine (p = 0.006) and urea (p = 0.012) and load adaption index , male gender , low TAPSE , high creatinine  and high CVP . Furthermore, GOT  and GPT  remained in the model.Early RHF was independently predicted by lower age , low thrombocytes  and low VTITR  as independent risk factors , low hemoglobin concentration  accordingly. The models’ AUC ranged from 0.747 to 0.805 Fig. . De LongRHF after LVAD implantation can appear as short-term as well as long-term complication. We show that both early RHF and late RHF are common and have a negative impact on patient outcome. RHF before LVAD implantation was associated with a higher risk of early RHF and persistent late RHF, but not for new onset late RHF. Single echocardiographic, laboratory and hemodynamic parameters did not strongly predict new onset late RHF. In our cohort, similar predictive value of clinical findings and statistic models of risk factors highlight clinical evaluation to predict RHF.Especially the prevalence of late and chronic RHF becomes increasingly important due to the growing number of patients with long-term LVAD support. Hitherto, no discrete factor with adequate discrimination and satisfying reliability was found. In a recent meta-analysis, the only predictors strongly associated with RHF were INR and CVP. Reduced cardiac index and high pulmonary vascular resistance were the main moderators of the relationship between INR and RHF .The vast majority of studies focus on patients that suffer from RHF early post LVAD implantation in order to identify patients needing a temporary RVAD implantation , 13–16. Takeda et al.  assessedTranspulmonary gradient (diastolic and/or mean) and corresponding pulmonary resistance are surrogates for right ventricular afterload and determine if a patient is eligible for transplant. They might also predict the risk for postoperative RHF and/or mortality in LVAD recipients . LVAD thIrrespective of the underlying mechanism, knowledge about whether or not and when a patient will develop RHF after LVAD implantation would enable clinicians to individually determine patient-adjusted strategies .Strategies to optimize right ventricular function before LVAD implantation are limited to patients with stable heart failure. Nevertheless, the benefit of prophylactic therapy with inotropic agents, pulmonary vasodilators and volume management by hemodialysis guided by CVP in order to prevent RHF is not clear .There are several definitions of RHF differing in criteria, time scope and severity. In most studies, RHF is defined as the requirement of unplanned RVAD implantation, nitric oxide or iloprost inhalation for more than 48 h or intravenous inotropic therapy for more than 14 days after surgery . For evaHere we could show that the predictive value of a model including three clinical findings  is equal to technical regression models.The main limitations of our study is the retrospective, mono-centric study design, and the sample size. We assessed a broad, but unquestionably limited set of parameters. Since the model development sample was used for model validation, generalization of results should be applied with caution. We excluded all patients who did not receive an HVAD and patients who underwent primary long-term BiVAD implantation. This might constitute as a selection bias, but it renders relevant homogeneity to our cohort.We chose a ‘broad’ clinical definition of RHF resulting in a high prevalence of RHF compared to other studies. As intra-operative variables such as volume, inotropic and transfusion management were not considered, their influence on outcome remains undetected.Hemodynamic parameters were not re-assessed in a regularly unless necessary for transplant evaluation. Consequently, we cannot report the impact of LVAD therapy on parameters of pulmonary hypertension.Our results show that RHF before LVAD implantation is associated with a high rate of ERHF after surgery and is a predictor for worse outcome. Assessment of pre-operative clinical findings can help to identify patients at risk that probably profit from aggressive pre-operative optimization of right heart function gained by diuretics, inotropes or hemodialysis.Late RHF was only partly associated with pre-operative or early RHF indicating that a regular re-evaluation of the right ventricular function is mandatory and could be helpful to prevent new onset of late RHF. This predictive model should be validated in a bigger LVAD cohort. In the age of growing importance of biomarkers and imaging modalities the importance of clinical findings should not be underestimated.Additional file 1: Supplemental Table 1. Risk factors for early and late RHF.Additional file 2: Supplemental Table 2. Risk factors for RHF and death from RHF after one month and one year.


With the improvement in survival rate, cardiotoxicity has emerged as a significant adverse effect of cancer therapy. Early diagnosis of subclinical cardiac injury may allow the initiation of cardioprotective therapy and preventing the interruption of optimal cancer therapy and the development of irreversible cardiac dysfunction. In this article, we review the role of two-dimensional speckle tracking echocardiography (2D-STE), beyond the common left ventricle global longitudinal strain in the diagnosis of early subclinical cardiac injury in patients treated with cancer therapies. Over the last several decades, the advance in cancer therapies has led to a significant increase in survival rate, with over 16 million cancer survivors in the United States to date . AlthougNumerous studies have shown that detection of early cardiac injury is crucial and may lead to full or partial recovery of the LV function with early intervention, either by adjusting the cancer therapy or by initiating cardioprotective treatment ,8,9. CurIn recent years, there is a rising use of 2D speckle tracking echocardiography (2D-STE), for the measurement of myocardial deformation as a marker of contractility and elasticity . The useIn this paper we focus on present and future role of 2D-STE, beyond the commonly used LV GLS, for the early diagnosis of subclinical cardiac injury in patients treated with cancer therapies.Longitudinal strain is derived from apical images reflecting the changes in the distance between two segments of the heart relative to their baseline distance apart  Figure . LV GLS Overall, the accepted normal cutoff value for LV GLS is ≤−18% . A studyBoth LV global circumferential strain (LV GCS)  and LV radial strain (LV GRS)  have wide range of normal values . The lowCommonly, the myocardial wall is subdivided into an epicardial, mid-myocardial, and endocardial layers. However, the clinical value of layer-specific assessment is questionable, mainly due to low visibility of the wall for tracking . AlthougDiastolic dysfunction is considered common among cancer patients; yet no clear evidence has shown that it can predict future LV systolic dysfunction . DiastolThe left atrium (LA) plays an important role in the regulation of filling pressure and LV diastolic function. The LA functions as a reservoir to blood returning from the pulmonary veins, as a conduit to blood flowing during early diastole to the LV and as a pump contracting in late diastole . Left atThere is a rising interest in the use of RV global longitudinal strain (RV GLS) in different populations, with an observation of reduced RV GLS in both preserved and reduced heart failure patients  Figure . Data onThe normal cut-off value of RV GLS is considered—18.2% and above . The proClearly, the role of RV is emerging as a marker of cardiac injury in cancer patients and may be at least as frequent as LV injury. However, its prognostic value remains to be proven by large prospective studies.Wright et al.  evaluateCV imaging prior to the beginning of cancer therapy provides estimation of preexisting cardiac damage and establishes baseline information for future changes. Currently there are recommendation for baseline and serial LVEF follow-up only among patients treated with ANT and trastuzumab (a type of HER2 targeted therapy) , however2D-STE is a reliable and sensitive marker of early cardiac injury with a high availability, low cost, no radiation and no nephrotoxic effect compared to other cardiac imaging modalities. It is recommended to use the same vendor’s machine and software version during serial follow-up examinations . Early rWhile the high value of LV GLS is well recognized, 2D-STE has wide and less familiar modalities, specifically diastolic strain, LAS and RV GLS that are showing a promising role in the diagnosis of early sub-clinical cardiac injury in patients treated with cancer therapies. Future large randomized studies are needed in order to evaluate the role of all 2D-STE modalities in cancer patients, both as a routine surveillance as well as a dictating tool for the beginning of cardioprotective therapy.


We hypothesized that the TRV/TAPSE ratio reflect both the patients’ functional capacity and the hemodynamic performance of the individual RV‐ pulmonary artery (PA) unit.The novel TRV/TAPSE ratio correlated positively and strongly with NYHA FC, thus highlighting its clinical usefulness in future PH diagnosis.Echocardiography is an easily available and, thus, preferred imaging modality to detect systolic right ventricular (RV) dysfunction, although quantification of any such cardiac impairment remains challenging. It has been previously reported that tricuspid annular plane systolic excursion (TAPSE) can be used for risk stratification of children with pulmonary hypertension (PH).2.We investigated 47 children and adolescents with PH . NYHA FC was determined by two independent pediatric cardiologists. At enrollment, all patients were clinically stable without any change of medication in the preceding 12 weeks. A TRV >2.8 m/s was considered as the cut‐off value to define elevated PAP in the absence of RV outflow tract obstruction. All children with PH underwent cardiac catheterization. PH was defined according to the most recent 2018 World Symposium of Pulmonary Hypertension: a mean pulmonary artery pressure (mPAP) of >20 mm Hg at rest, a pulmonary arterial wedge pressure of ≤15 mm Hg, and a PVRi of >3 WU x mU test or t‐test) for the comparison of the groups to each other were performed. Data are presented as median and interquartile range (IQR), unless otherwise stated. Age‐specified TAPSE z‐scores were calculated according to the reference values provided by Koestenberger et al.P‐value < 0.05 was considered significant. Group comparisons for continuous variables were analyzed using the Kruskal‐Wallis H‐test or ANOVA, as appropriate. Afterwards, a post hoc test (Mann‐Whitney z‐score had a median of −2.79 (IQR: −7.37 to −2.39). The TRV/TAPSE ratio (m/s:cm) ranged from 1.53–8.40  in our patients (Table  P < 0.001); in contrast TAPSE z‐scores  decreased. With worsening NYHA FC, the TRV/TAPSE ratio  increased . Median TRV was 4 m/s (IQR: 3.5–4.3 m/s) and median PVRi was 6.2 WUxm2 (IQR: 3.7–9.2). The age‐specific TAPSE ts Table . With woIn 2009, we established TAPSE as a valuable echocardiographic measure of systolic RV function in childhood.This is the first pediatric study on this specific combinatory echocardiographic parameter approach, i.e., the TRV/TAPSE ratio (m/s:cm), in a mid‐sized cohort of children with PH. We have since found that the TRV/TAPSE ratio might be associated with worsening NYHA FC in our pediatric PH patients. In our experience, TAPSE values become abnormally low in the later stages of PH/hypertensive pulmonary vascular disease, which may explain its good, inverse correlation with clinical outcome;A major limitation of this preliminary study is that because of the small sample size, our novel TRV/TAPSE ratio could not be sufficiently compared to other prognostic variables. Therefore, future (multicenter) studies are warranted to provide sufficient statistical prognostic relevance of this novel parameter.In summary, we found that the TRV/TAPSE ratio increased with NYHA FC in children with PH. In future, multicenter studies related to PH and the TRV/TAPSE ratio maybe established as a potential parameter of clinical outcome.GH currently receives grant support from the German Research Foundation . The authors declare no conflict of interest.M.K. is the main author and wrote the manuscript; A.A. and K.M. collected and analyzed data; M.C. drafted the manuscript and G.H. critically reviewed the manuscript and supervised the study process. All authors read and approved the final manuscript. Table S1 Demographic data.Click here for additional data file.


A 54-year-old female, with a history of prosthetic mitral valve replacement due to mitral valve prolapse one year prior, was admitted after suffering a cardiopulmonary arrest. Her initial rhythm demonstrated Torsade de Pointes with the initial electrocardiogram (ECG) showing a prolonged QT interval. Laboratory test results were normal including potassium and magnesium serum levels, and imaging did not show significant abnormalities. A review of patients' medicines showed that the patient started taking escitalopram one month prior to the presentation for major depressive disorder. Selective serotonin reuptake inhibitors (SSRI) are widely prescribed and continue to be a mainstay of treatment for multiple psychiatric conditions. It is important to keep the potential cardiovascular side effects of SSRIs in mind when prescribing. Consideration of underlying cardiac conditions is vital to decrease the likelihood of poor outcomes. Selective serotonin reuptake inhibitors (SSRIs) are a class of medications widely used in primary care for a variety of common disorders such as depression, anxiety, post-traumatic stress disorder, and chronic pain. QTc prolongation is a well-documented side effect of this class , with ToStructural heart disease increases the risk of developing an arrhythmia; the presence of mitral valve prolapse (MVP) is associated with an increased risk of ventricular arrhythmias and sudden death. Arrhythmias have been known to persist even after the replacement of the defective valve . AlthougA 54-year-old female, with a history of prosthetic mitral valve replacement due to mitral valve prolapse one year prior, was admitted after suffering a cardiopulmonary arrest. Cardiopulmonary resuscitation was initiated by bystanders and continued by emergency medical services (EMS). The initial recorded rhythm was Torsade de Pointes which degenerated to coarse ventricular fibrillation Figure , requiriSSRIs are commonly selected for the treatment of depression due to their efficacy and wide therapeutic index . Though The relationship between QTc prolongation, Torsade de Pointes, and ventricular fibrillation has been well established . SSRIs, There are no clear guidelines regarding electrocardiographic monitoring in patients taking SSRIs, likely due to the relative rarity of severe arrhythmias. QTc prolongation and TdP related to SSRI are infrequent and sporadic and are usually associated with toxic drug levels or drug overdose excluding people who are at higher risk . A baselThis case serves to highlight the danger of using QTc prolonging agents in patients with a history of structural heart disease such as mitral valve prolapse, even after corrective repair. It is imperative that physicians be aware of the adverse cardiovascular effects of the SSRI including QTc prolongation and TdP. In our opinion, an initial EKG is warranted before prescribing SSRIs in the presence of structural heart disease including MVP. We feel that surveillance ECGs should be obtained when increasing medication dosage. Patients should also be educated regarding the potential adverse effects of the medication class.