The number of cases for which the Batista procedure is indicated is small, but some patients with appropriate indication can achieve good therapeutic results.To avoid incorrect left ventricular incision and obtain good surgical results in patients with dilated cardiomyopathy suitable for partial left ventriculectomy, we employed intraoperative direct echocardiography to determine the exact extent and position of the myocardial incision, even for surgeons who are not very experienced with the Batista procedure.A 72-year-old man with dilated cardiomyopathy underwent the Batista procedure with the aid of epicardial echocardiography to confirm the location of both the papillary muscles and the diseased myocardium.We were able to accurately perform left ventricular incision and remove the diseased lateral ventricular wall. Two years later, the patient had no symptoms of heart failure, and his brain natriuretic peptide (BNP) level decreased from 1155 to 49.3 pg/mL.We believe that the use of intraoperative echocardiography may have the potential to make the Batista procedure less technically demanding and more reproducible for surgeons with little experience in the procedure. Although there are many reports on the Batista procedure, few have shown that it is effective and associated with a good long-term prognosis, so it is not currently performed at many facilities. Few patients have lesion confined to the posterolateral side of the myocardium, and few surgeons perform Batista procedures according to strict criteria., and if they are appropriate candidates for treatment, this procedure may be an effective option. There may be some patients who need this surgery to improve their heart failure.However, some patients can obtain good therapeutic results, as reported by Batista et al.We experienced a case in which intraoperative epicardial echocardiography was used to confirm the location of both the papillary muscles and the diseased myocardium, and it was possible to plan the resection site before surgery. This method may be an effective intraoperative diagnostic tool as an aid to surgeons performing the Batista operation who do not have much experience with the procedure. We report our experience in this article.2, cardiac output (CO) 2.2 L/minute, cardiac index (CI) 1.5 L/minute/m2. Single-photon emission computed tomography image of exercise 99mTc-methoxy isobutyl isonitrile (MIBI) scintigraphy revealed defect of concentration in the posterior wall and myocardial infarction tracer showed a negative scintigram.Our patient was a 72-year-old man who had been followed for 4 years at an outside hospital for severe chronic systolic heart failure due to dilated cardiomyopathy and mitral regurgitation (MR). He had been diagnosed with atrial fibrillation four years ago, but the exact time of onset was unknown. With medical management  alone, his disease had progressed, leading to exertional dyspnea. From these findings, our policy was to treat with surgery. On admission to our institution, his height was 153.5 cm, body weight 59.1 kg, blood pressure 98/64 mmHg, heart rate 64 bpm and the rhythm was atrial fibrillation. Electrocardiography revealed atrial fibrillation without f-wave and no left bundle branch block. Echocardiography showed severe MR resulting from tethering and moderate tricuspid regurgitation (TR). Left ventricular (LV) end-diastolic and end-systolic dimensions (LVEDD/LVESD) were 75/66 mm, left ventricular volumetry were 341/225 mL, interventricular septal wall thickness in the end diastole (IVSd) was 11 mm, left ventricular posterior wall thickness in the end diastole (LVPWd) was 5 mm, interpapillary muscle distance was 39 mm and the LV ejection fraction was 28% (modified Simpson’s method). Peak early diastolic filling velocity (E-wave), peak late diastolic filling velocity (A-wave) and their ratio (E/A) was 1.37. The E/e’  was 14.43. The LV wall showed global hypokinesia and inferoposterior dyskinesia. The chest X-ray revealed bilateral pulmonary congestion. The chest thoracic ratio was 72%. His preoperative BNP was 1155 pg/mL. Coronary computed tomography (CT) revealed no vascular stenoses. Cardiac catheterization showed left ventricular end-systolic volume (LVESV) 267.6 mL, left ventricular end-diastolic volume (LVEDV) 395.2 mL, left ventricular end-systolic volume index (LVESVI) 180 mL/mThe patient’s dilated cardiomyopathy was due to global hypokinesia and lateral wall dyskinesia. We thus decided to perform the Batista procedure. We did not choose maze procedure and cardiac resynchronization therapy because both were thought to be not effective. To establish a postoperative LVEDD of 62 mm, 40 mm of ventricular tissue needed to be removed . As a prUnder local anesthesia, an intra-aortic balloon pump (IABP) was inserted into the left femoral artery. The IABP was initiated before the introduction of general anesthesia. The procedure was performed on-pump, with a beating heart and without aortic cross-clamp . The antPostoperative echocardiography revealed LVEDD/LVESD of 62/43 mm and LV ejection fraction of 30% (modified Simpson’s method). Mitral regurgitation was not observed (tethering was improving). Three weeks after surgery, the patient was discharged from our hospital without further complication. Histopathological findings revealed the presence of abnormal nuclei  and loss of striation. Fibrosis was characteristically interstitial and began to surround and isolate individual myocytes. There was no contradiction as a finding of dilated cardiomyopathy.Two years later, the patient had no symptom and his BNP level decreased from 1155 to 49.3 pg/mL . Echocar,2 The procedure improves LV function by decreasing LV diameter via excision of the diseased LV free wall. Here, we report the use of the Batista operation in a patient with end-stage cardiomyopathy, with dyskinesia of the posterolateral wall between the anterior and posterior papillary muscles, and a dilated LVEDD ≥75 mm. For this patient, we aimed for a postoperative LVEDD of 65 mm. The Batista operation consisted of a wide excision of the posterolateral wall between the anterior and posterior papillary muscles.The Batista operation has been shown to improve survival in carefully selected patient populations introduced the echo-guided volume reduction test and evaluated its effects on surgery for dilated cardiomyopathy. Here, we report the first use of direct intraoperative echocardiography to select the location of the surgical incision line.The choice of LV excision or exclusion site is difficult, even for experienced cardiac surgeons. We used direct intraoperative echocardiography to select the site of LV excision. Echocardiography allowed us to detect the diseased LV wall region and the location of the anterior and posterior papillary muscles. Isomura, suitable patient selection and proper surgical technique may improve LV function and provide effective treatment. Isomura et al. recently noted that surgeons will be able to select several options for the treatment of congestive heart failure; this includes the use of mechanical support devices and the use of implantable ventricular assist devices as target therapy. Posterior cardiac restoration was one of these treatments, and the most important issue was understanding the advantages and disadvantages of these surgical treatments.Although in many countries the Batista operation has been largely abandoned following a negative report from the Cleveland ClinicFew cases are suitable for the Batista procedure; hence, a clear and reproducible technique is crucial to success. The addition of intraoperative echocardiography may provide benefit during the Batista procedure.Our proposed use of intraoperative direct echocardiography was useful in making the Batista procedure less technically demanding. It may be reproducible in patients with end-stage heart failure.


N-oxide (TMAO) and odds of diabetic retinopathy (DR).To determine the relationship between plasma levels of trimethylamine-A cross-sectional study was conducted. Blood samples were obtained from 122 type 2 diabetes mellitus (T2DM) patients with or without DR. Multivariable logistic regression analyses were performed to identify the association between plasma TMAO and DR. The diagnostic value of plasma TMAO was assessed by the area under the receiver operating characteristic curve (AUROC) and integrated discrimination improvement (IDI).P = 0.001). As logarithmic (ln) transformation of TMAO increased per standard deviation (SD), there was higher probability to have DR . As ln-transformed TMAO increased per SD, the severity of DR was more likely to get worse . In the diagnostic model, the addition of TMAO contributed to the improvement in AUROC from 0.646 to 0.734 (P = 0.043), and the IDI was 10.7% (P < 0.001).In the T2DM patients, plasma levels of TMAO were significantly higher in patients with DR compared with those without DR (Elevated levels of plasma TMAO were associated with higher odds and worse severity of DR in T2DM patients, and further investigation is required for the causality of this association. Diabetic retinopathy (DR), the ocular manifestation of end-organ damage in diabetes, is a major cause of vision impairment in middle-aged and elderly individuals . The gloN-oxide (TMAO), a gut microbiome-derived metabolite, is mainly produced from dietary L-carnitine, choline and its precursor trimethylamine (TMA). Gut microbiota transform L-carnitine and choline into TMA, which is further oxidized in liver into TMAO by flavin-dependent monooxygenase 3 (FMO3) [Trimethylamine-3 (FMO3) . A wealt3 (FMO3) , and rec3 (FMO3) , 7 or ge3 (FMO3)  can markA recent meta-analysis revealed positive dose-dependent association of plasma TMAO with risk of diabetes . Higher The evidence above implies that TMAO might be a promising biomarker for diabetes-related diseases. However, to our best knowledge, there is no reported data identifying the association between TMAO and DR. Hence, we performed this study to investigate whether plasma TMAO levels are associated with presence of DR in patients with type 2 diabetes mellitus (T2DM).https://www.chictr.org.cn). One hundred and sixty-two inpatients at the First Affiliated Hospital of Soochow University from July 2019 to December 2019 were enrolled in this cross-sectional study. Patients of diabetes without DR (DWR) and nonproliferative DR (NPDR) were enrolled from the Department of Endocrinology, who were in hospital due to poor glycemic control and further checked fundus condition in the Department of Ophthalmology. Proliferative DR (PDR) patients and non-diabetic patients with idiopathic macular hole were enrolled from the Department of Ophthalmology, who were in hospital for vitrectomy. Participants of Chinese Han ethnicity aged 40–85 years old were defined as eligible. T2DM was diagnosed based on either the fasting plasma glucose (FPG) of ≥ 7.0 mmol/L, or glycated hemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol), or a previous diagnosis of T2DM according to Standards of Medical Care in Diabetes . We did Clinical data were obtained from medical records, including age, gender, duration of diabetes mellitus, history of hypertension, coronary heart disease (CHD) and diabetic nephropathy (DN). Body mass index (BMI) was calculated using weight and height measurements. Overnight fasting venous blood samples were collected on the second day morning of admission and sent to the clinical laboratory center of our hospital within 1 h for further analyses of FPG, HbA1c, serum creatinine (SCr) and lipid profiles including triglyceride, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C). Estimated glomerular filtration rate (eGFR) was calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation .The quantitative detection of plasma TMAO concentration was performed in Physical and Chemical Laboratory of Suzhou Center for Disease Control and Prevention by stable isotope dilution liquid chromatography–tandem mass spectrometry (LC–MS/MS) method as described elsewhere . Plasma 9-TMAO  in methanol, then followed by vortex for 30 s and centrifugation at 12,000 rpm at 4 °C for 10 min. The precipitation was discarded and the supernatant was recovered and centrifuged again in the same way. Afterward, 2 µL of supernatant was injected into ACQUITY UPLC BEH HILIC column  at a flow rate of 0.2 ml/min and subsequently analyzed using Waters ACQUITY UPLC I-Class/Xevo TQD System . In order to elute the analytes, a gradient elution was generated by mixing solvent A (10 mmol/L ammonium acetate in water) and solvent B (acetonitrile) at following different ratios. The proportion of solvent A increased linearly from 20 to 80% within 1.8 min, maintained constant at 80% for 1.8 min, and then decreased linearly back to 20%. Electrospray ionization (ESI) in the positive ion mode was conducted with multiple reaction monitoring (MRM) using characteristic precursor–product ion transitions as follows: TMAO at m/z 76 → 58 and d9-TMAO at m/z 85 → 66. A standard curve was established by using a serial dilution of TMAO standard  mixed with a fixed concentration of d9-TMAO  and the correlation coefficient (r2) was 0.999. The peak area ratio of TMAO and d9-TMAO was used to quantify TMAO concentration with MassLynx v4.1 software . All of the assays were performed blind.Briefly, 50 µL plasma sample was mixed with 200 µL pre-prepared internal standard, which contains 500 µg/L dP < 0.05 (two-tailed). Continuous variables were expressed as mean with standard deviation (SD) or median with interquartile range (IQR) based on normality of data distribution assessed by Shapiro–Wilks test. We applied a logarithmic (ln) transformation of TMAO values to obtain normally distributed data [ U test for nonparametrically distributed data. Differences among multiple groups were analyzed using one-way ANOVA and Kruskal–Wallis test for means and medians, respectively, and Bonferroni post hoc pairwise comparison was performed when necessary. For categorical variables, data were presented as number with percentage and compared using Chi-Square analysis. Spearman rank correlations were analyzed between levels of plasma TMAO and other continuous variables in T2DM patients. Tukey box and whisker plots were graphed using GraphPad Prism Version 8.0 .All statistics were performed using the SPSS 24.0 software  and statistical significance was set at ted data . CompariP value for interaction. Furthermore, ordinal logistic regression was employed to determine the relationship between plasma TMAO concentrations and DR severity. In multivariable logistic regression models, we adjusted age and gender in Model 1, and further adjusted BMI, diabetes duration and hypertension in Model 2. To assess whether this association was influenced by renal function, we further adjusted eGFR in Model 3.To identify the association between plasma levels of TMAO and DR in T2DM patients, we used binary logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for DR across quartiles of plasma TMAO and per SD increment in the ln-transformed TMAO . We furtYouden index. The primary diagnostic model involved the widely known risk factors for DR, including age, gender, BMI, diabetes duration and hypertension, and we then compared the AUROC before and after adding TMAO as a new factor into the model. Besides, integrated discrimination improvement (IDI) was estimated as well to assess the additional effect of TMAO in diagnosing DR [The area under the receiver operating characteristic curve (AUROC) was generated by MedCalc Version 19.0.7  to assess the value of TMAO in diagnosing DR. The optimal cutoff value was determined using the maximal osing DR .The study population consisted of 122 T2DM patients  and 40 non-diabetic patients (set as control). As shown in Table P < 0.001; Table P < 0.001). All DR patients displayed higher TMAO concentrations than DWR patients .Tukey box and whisker plots showed the distribution of plasma TMAO concentrations Fig. . The ranr = 0.314, P < 0.001), diabetes duration  and SCr , and were negatively correlated with eGFR , but were not correlated with BMI and lipid profiles in T2DM patients (Table The Spearman rank correlation coefficients showed that plasma levels of TMAO were positively correlated with age (P-trend < 0.001) after adjusting the covariates . After adjusting the covariates included in Model 3, this association remained significant .In univariate ordinal logistic regression model, we found that per SD increment of ln-transformed TMAO was correlated with worse DR severity  with optimal cutoff value of 0.761 µmol/L yielded 50% sensitivity and 86% specificity. The AUROC was 0.646  for the primary diagnostic model and 0.734  for a new model combining the acknowledged factors and TMAO, indicating statistical improvement in AUROC due to the addition of TMAO as 0.088 . We also found that the addition of TMAO resulted in improvement of discriminatory power of the model .As shown in Fig. In the present study, we found a novel relationship between plasma TMAO and DR, which has not been reported before as far as we know. Plasma levels of TMAO significantly elevated in DR patients compared with DWR patients and were correlated with DR severity. Our results provided preliminary evidence supporting that higher plasma TMAO levels were independently associated with increased odds of DR in T2DM patients. Prospective cohort studies with larger sample are required to further determine the causal relationship.It was surprising that age and diabetes duration showed no significant difference among DWR, NPDR and PDR groups, and FPG and HbA1c levels in PDR group were lower than those in DWR and NPDR groups in this cross-sectional, hospital-based study. These results were inconsistent with previous reports , 20 and Our quantitative analyses revealed lower plasma TMAO concentrations in the subjects of Chinese Han ethnicity compared with Western population . This miRecent studies suggested that increased plasma TMAO portended more CVD events, worse renal outcome, and higher mortality risk independent of glycemic control and other conventional risk factors for diabetes , 22, 23.Logistic regression analysis showed the relevance between TMAO and presence of DR in T2DM patients. All of the univariate and multivariate results demonstrated that patients categorized into the highest quartile of plasma TMAO concentrations were more prone to DR. Odds of DR approximately doubled as the ln-transformed TMAO increased per SD. Beyond that, this association was found stronger in male patients through subgroups analyses. The interaction effect between plasma TMAO and gender may be partly explained by the sex differences in dietary pattern, gut microbiome composition , 27, butWhen analyzing the plausibility of applicating plasma levels of TMAO into DR diagnosis, the results showed low value of TMAO alone for DR diagnosis. However, through comparison of AUROC and calculation of IDI, we found that the discriminative ability of the model improved after addition of TMAO into the model with known risk factors. These results indicated an application prospect of plasma TMAO in clinical management of DR, and future study should make further efforts to confirm the application value of TMAO by enrollment of a larger population.Our study detected a relationship between plasma TMAO and presence of DR, but up to date, the exact causal direction of this association remains unclear. It was indicated that diabetic gut microbiota dysbiosis could promote DR development , and gutFirstly, TMAO might take part in DR development by enhancing insulin resistance and dyslipidemia. As noted previously, higher levels of plasma TMAO were correlated with greater insulin resistance and less improvement of the diabetes-related outcomes , 32. Besα and IL-1β and decreased levels of IL-10 [Secondly, systemic inflammation might be another mechanism. Inflammation serves as a pivotal mechanism governing the progression of DR . Elevateof IL-10 .Thirdly, vascular inflammation and endothelial dysfunction could be involved. TMAO could directly activate inflammatory signaling pathway and facilitate recruitment of leukocytes , 39. It However, several limitations should be considered when interpreting our results. Firstly, the cross-sectional design might enhance selection and recall bias, and our study could not identify the causal direction between TMAO and DR. Secondly, our limited sample size caused insufficient representativeness of the general population as well as large confidence intervals in logistic regression analyses. Thirdly, we did not use nutritional epidemiology methods to record detail dietary pattern and food intake data, and we did not examine plasma choline, TMA and composition of intestinal flora, which were related to TMAO generation. Fourthly, aqueous and vitreous levels of TMAO were not evaluated in our study, and future study should compare the TMAO concentrations across different body fluid. Finally, different lifestyle factors and comorbidities relevant to the disease were not considered, which might potentially influence the results.In conclusion, our study demonstrated elevated plasma levels of TMAO associated with higher odds and worse severity of DR in T2DM patients. Further studies with prospective cohort study design are warranted to establish causal relationship and to elucidate the exact molecular mechanisms underlying this association in detail.


To the editor,Clinical Cardiology.We would like to thank Kosuke Miki and Teruhiko Imamura for their thoughtful comments regarding our article titled “Cardiovascular Manifestations in Severe and Critical Patients with COVID‐19,” which was published last month in In response to the concerns regarding the echocardiographic methodology of how to assess heart failure, we included strain assessment and tissue Doppler analyses during the assessment. We used ejection fraction (EF) as a measurement of left heart failure and tricuspid annular plane systolic excursion (TAPSE) as a measurement of right heart failure. We agreed that measurement of QRS duration could help assess the electrocardiographic myocardial injury, but we mainly evaluated the severity of myocardial injury by the concentration of cardiac troponin I (cTnI) and creatinine kinase‐MB isoenzyme (CK‐MB). Six patients  had a previous history of coronary artery disease. It is a pity that we did not apply angiography or computed tomography angiography (CTA) to survey the coronary artery for other patients, considering their severe condition. Time course of COVID‐19 was also our concern previously. But by the time we collected and analyzed the clinical data, the patients were all during treatment and we could not predict the final outcomes (live or death). So we focused our attention on analyses of risk factors for critical status at the time. And we did a follow‐up of these patients continuously. As for the third concern, we did not apply beta‐blocker in all these patients considering that beta‐blocker might exacerbate the lung condition.


There is an established role for magnetic resonance imaging in the assessment of myocardial fibrosis, in ischaemic and non-ischaemic cardiomyopathies. The amount of fibrosis is of importance because of its prognostic value, in terms of arrhythmias occurrence, and haemodynamic consequences.T2 relaxation time directly depends on physico-chemical properties of each tissue. Thus, myocardial T2 time determination can help in quantifying fibrosis. Diabetic cardiomyopathy is characterized by myocardial structural modifications including hypertrophy, microcirculation impairment and interstitial fibrosis.To describe a non-invasive MRI method using high-resolution myocardial T2 time measurement to assess myocardial fibrosis in a model of diabetic mice in vivo.Two multi-slice spin-echo sequences were performed for T2 time assessment respectively at 20 and 9 ms echo time , in ten 16-week old C57Bl/6J after 8 weeks of streptozotocin-induced diabetes, and ten control mice, under isoflurane anesthesia using a 11.75 T vertical scanner . All images were acquired in short-axis view. MRI measurements were then compared with histological quantification of fibrosis using picrosirius red staining.T2 relaxation time was significantly lower in diabetic mice . This was associated with a significant increase of myocardial fibrosis as evaluated by picro-sirius red staining, in diabetic mice.We describe here a non-invasive and accurate MRI method to quantify myocardial fibrosis in vivo in diabetic mice, using T2 relaxation time measurement. This method can be applied in many ischaemic or non-ischaemic cardiomyopathies in which a fibrotic phenomenon is involved.


Background and objectivePre-eclampsia (PEC) is associated with the release of anti-angiogenic factors that are incriminated in raising systemic and pulmonary vascular resistance (PVR). Compared to the left heart and systemic circulation, much less attention has been paid to the right heart and pulmonary circulation in patients with PEC. We used transthoracic echocardiography (TTE) to estimate pulmonary artery (PA) pressure and right ventricular (RV) function in women with PEC.Materials and methodsWe conducted a case-control study at a tertiary care academic center. Ten early PEC (<34-week gestation) and nine late PEC (≥34-week gestation) patients with 11 early and 10 late gestational age-matched controls were enrolled. Two-dimensional TTE was performed on all patients. The estimated mean PA pressure (eMPAP) was calculated based on PA acceleration time (PAAT). PVR was estimated from eMPAP and RV cardiac output (RV CO). RV myocardial performance index (RV MPI), tricuspid annular plane systolic excursion (TAPSE), tissue tricuspid annular displacement (TTAD), and lateral tricuspid annular tissue peak systolic velocity (S’) were measured.ResultsCompared to early controls, in early PEC, the eMPAP and estimated PVR (ePVR) were elevated, PAAT was reduced, RV MPI was increased, TTAD was reduced, and TAPSE and TV S’ were unchanged. Compared to late controls, in late PEC, the eMPAP and ePVR were elevated, PAAT was reduced, and RV MPI was increased, while TAPSE, TTAD, and TV S’ were unchanged.ConclusionsIn a sample of women with PEC, early PEC was found to be associated with increased eMPAP and ePVR and subclinical decrement of RV function as assessed by TTE. TTE may be a useful noninvasive screening tool for early detection of pulmonary hypertension and RV dysfunction in PEC. An adequately powered longitudinal study is needed to determine the implications of these findings on long-term outcomes. Pre-eclampsia (PEC) is a leading cause of maternal and perinatal morbidity and mortality worldwide, affecting 1-7% of all pregnancies . The incPEC is a vascular disease characterized by the placental production of anti-angiogenic factors such as the soluble form of fms-like tyrosine kinase (sFLT) and soluble form of endoglin (s-ENG). These anti-angiogenic factors by the placenta interfere with adequate placentation, promote a high systemic vascular resistance and placental ischemia or hypoxia, leading to maternal and fetal endothelial dysfunction ,6. RecenLeft ventricular (LV) function and systemic circulation has been studied extensively, by using echocardiography in PEC . Much leIn this study, we utilized echocardiography to explore the changes in RV function and pulmonary circulation in women with early (<34-week gestation) and late PEC (≥34-week gestation). We hypothesize that PEC is associated with echocardiographically estimated RV dysfunction and pulmonary hypertension compared to matched controls.Study designA cross-sectional study was carried out at the University of Alabama at Birmingham from June 2016 to December 2016 after obtaining approval from the institution's Institutional Review Board (IRB-170119002); written informed consent was obtained from all subjects.Study populationThe inclusion criteria were as follows: adult patients with singleton pregnancy meeting the definition of PEC according to the revised ACOG 2013) criteria  + RV isovolumic relaxation time (IVRT)/RV ejection time (ET) . RV ET wApical four-chamber views were specifically optimized to visualize the RV to obtain echocardiographic cine loops by recording three consecutive heart cycles with a frame rate of >60 frames/second. Offline analyses were performed using dedicated software . To assess tissue-tracking tricuspid annular displacement (TTAD), three user-defined points were selected in the RV-focused view as follows: at the point of insertion of the lateral (TTAD L), and septal (TTAD S) leaflets, and at the midpoint (TTAD MP) of the tricuspid valve to the tricuspid annulus and the RV apex. The software automatically tracked the TTAD and calculated the TTAD at the RV free wall, the TTAD at the interventricular septal wall, and the TTAD at the midpoint of the TV annulus, as well as the percentage displacement of the midpoint (TTAD MP %). In some patients , the image quality was inadequate to reliably assess TTAD, and in the case of one patient, there was no agreement between the two observers, resulting in the patient's exclusion from the analysis. The apical four-chamber and the PSAX views were used to measure LV EF by the area-length technique . LV endoEstimation of PA Pressure by EchocardiographyWe initially attempted to estimate PA systolic pressure by using the Bernoulli equation (PAP = 4 x TRvel2) from the tricuspid regurgitation jet velocity, in case a tricuspid regurgitant jet was discerned . Since wSince the tricuspid regurgitant jet was not discerned in most cases, the mean pulmonary artery pressure (MPAP) was estimated from the pulmonary artery acceleration time (PAAT) measured across the pulmonary valve using pulsed Doppler waveform by using a logarithmic equation according to the formula validated by Kitabatake et al.  and YareeMPAP = 10-0.0068*(PAAT) + 2.1The PAAT-based analysis was also analyzed by categorical assessment using a cutoff value of PAAT = 100 ms. According to this formula, it was shown that in non-pregnant individuals, PAAT of <100 ms predicts pulmonary arterial hypertension (PAH) and increased pulmonary vascular resistance (PVR) with a sensitivity of 84% and specificity of 90% .PVR was estimated from eMPAP and RV CO using the following formula :‘Estimated PVR (ePVR) = eMPAP/RV CO’Estimation of Left Atrial Pressure by EchocardiographyIn order to discern whether the elevated MPAP is due to left heart disease versus an increase in ePVR, we utilized a noninvasive method to estimate the filling pressure for the LV, which is based on measuring the E and A waves of the mitral valve (MV) flow velocity and by measuring the velocity of the mitral annulus (e’). Mitral E/A of >2 and E/e’ of >14 show a good correlation with elevated LV filling pressures . Statistical analyseshttp://vassarstats.net/fisher2x4.html), followed by pairwise Fisher’s exact test with Bonferroni’s correction. A p-value of <0.05, after applying the correction for multiple comparisons, was considered to be statistically significant. Inter-observer reliability was determined by using Bland-Altman methodology and expressed as bias (mean difference) and 95% limits of agreement (2 X SD mean difference). The correlation between eMPAP and mean arterial pressure (MAP) was analyzed using linear regression analysis. Since this was an exploratory study with the main purpose to determine whether a larger study was warranted, the sample sizes were not based on power calculation.Statistical analyses were performed using the Prism software , unless noted otherwise. The primary variables for assessing the differences were eMPAP and PAAT. Since the estimated PA pressure was directly calculated from PAAT, we considered these as a single primary variable. All other variables reported are secondary variables. Continuous variables were presented as mean ±standard deviation. The normality test was calculated by four different methods automatically by Prism: Anderson-Darling (A2*) (AD), D'Agostino-Pearson omnibus (K2) (DP), Shapiro-Wilk (W) (SW), and Kolmogorov-Smirnov (distance) (KS). PAAT, RV MPI, maternal age, gestational age at admission, diastolic BP, heart rate, RV FAC, RV cardiac index (COi), and TAPSE passed the normality tests by all four methods; estimated PA pressure, RV stroke volume index (SVi), systolic BP passed three tests; BMI, ePVR, TTAD S, and TTAD MP % passed two tests; MV E/e’, TTAD L, and TTAD MP only passed DP; MV E/A only passed KS; mean BP and gestational age at delivery did not pass any of the tests. For variables that were not normally distributed. we used the Kruskal-Wallis test with Dunn’s post-hoc analysis. Variables that tested at least three normality tests were considered to be continuous variables, and a two-way analysis of variance (ANOVA) was used with Bonferroni’s post-hoc analysis. Categorical variables were analyzed by using Fisher’s exact test for 2 x 4 tables initially , withdrawn consent (two), technical difficulties with echo (one), and non-reassuring fetal heart tones (one), leaving 40 patients for final analysis. The 40 women studied were classified into four groups as follows: early PEC n=10), matched early controls (n=11), late PEC (n=9), and matched late controls (n=10). The demographic and clinical characteristics of the study groups are presented in Table 0, matcheSystolic arterial pressure was significantly higher in the early and late PEC groups as compared to the corresponding control groups Table . The difThe eMPAP was within the normal reference range (8-20 mmHg) in the early control group , whereas eMPAP in the early PEC group was above the normal reference range , and it was significantly higher than the early control group  Figure . SimilarAt a PAAT cutoff of 100 ms, there were significantly more patients with early PEC that had a PAAT of <100 ms compared with early controls Table . There wRV FAC, indexed RV stroke volume, indexed RV CO, MV E/A, MV E/e’, TAPSE, and TV S’ were not significantly different across any of the groups Table .TTAD lateral was not significantly different across groups, but TTAD midpoint, TTAD septal, and TTAD midpoint % were all significantly decreased in early PEC vs. early controls Table  Figure .The Bland-Altman assessment of PAAT between both observers showed a bias close to 0 (0.455) and the SD of bias was 8.61, revealing that there was no systematic bias between the two observers Figure .The data shown in Figure In this exploratory study, we demonstrated echocardiographic evidence that suggests a subclinical increase in eMPAP and ePVR, and a modest decrement in RV function in patients with an established diagnosis of early and late PEC compared with age- and gestationally-matched pregnant controls. PAAT at a cutoff value of 100 ms differentiated patients with early PEC compared with controls, substantiating the likelihood of increased PA pressure. Likewise, validated equations that estimate MPAP based on PAAT revealed an increase in eMPAP in PEC compared with controls. ePVR was significantly elevated in both early and late PEC compared to controls. We detected significantly increased RV MPI and reduced midpoint TTAD in early PEC. Other parameters of RV function, such as RV FAC, indexed RV stroke volume, indexed RV CO, tricuspid annular systolic excursion, and TV peak annular tissue velocity were unchanged. In the absence of clinical or echocardiographic evidence of valvular, or systolic, or diastolic LV dysfunction, we speculate that the increased eMPAP, decreased PAAT, and increased ePVR were due to a pulmonary vascular phenomenon rather than a left heart disease etiology. Our study highlights the potential value of echocardiography as a bedside noninvasive tool in the assessment of cardiac structure and function in PEC patients.Noninvasive assessment of the pulmonary circulation and RV function and structure in PEC is an evolving area of investigation. We are aware of only two studies assessing PA flow dynamics noninvasively in PEC, and both of those studies corroborate our findings in general, although by using a slightly different methodology (without distinguishing between early- and late-onset PEC and without excluding patients with severe PEC) ,18. SignA recent meta-analysis of 21 published studies has indicated that the estimation of MPAP using PAAT shows a very good correlation with values obtained using catheterization, that a cutoff value of PAAT of <100 ms has 84% sensitivity and 90% specificity in the diagnosis of pulmonary hypertension, and that PAAT can be reliably measured in >90% of patients . In our In our early PEC cohort, we found the estimated MPAP to be above the maximum of the normal range. Both Çağlar et al.  and VaugTo the best of our knowledge, our study is the first one to assess TTAD in pre-eclamptic patients. By representing the tricuspid annulus at three points, TTAD may be more representative of the entire longitudinal motion of the tricuspid annulus compared with TAPSE that only measures the free wall tricuspid annular displacement. TTAD L shows a close correlation with TAPSE, and TTAD MP has been shown to be more predictive of RV dysfunction in patients with PAH compared with TAPSE  and to bReduced RV function in PEC has been shown in previous studies, albeit with the use of different indices of assessment ,22. The Preexisting PAH portends increased mortality in pregnancy and the current recommendation for patients with preexisting pulmonary hypertension is to avoid becoming pregnant, due to a 15-40% incidence of mortality among women who become pregnant with preexisting PAH . There iOur study was exploratory in nature and was designed to provide a proof of concept of the importance of screening for the right heart and pulmonary circulation in PEC and the feasibility of accomplishing this noninvasively. The findings of our study need to be validated using a larger cohort, which will also allow for correlating echocardiographic estimates of MPAP and PVR with indices of disease severity and long-term outcomes. The small sample size precluded appropriate adjustment for comorbidities, which should be addressed in subsequent larger studies. Seven of the 19 PEC patients in this study received antihypertensive therapy during the echo exam, which may have altered the echocardiographic findings compared with controls. However, none of the three drugs, labetalol, hydralazine, or nifedipine, are likely to cause an increase in PA pressure as we observed in this study in the PEC group. Instead, all three drugs have been proposed in the past to be used to treat PAH, although they were not shown to be effective.Given the cross-sectional design of our study, our echo exams were conducted very close to, yet before, the delivery. Hence the findings may represent a mixed pattern of pregnancy and labor rather than a single pattern. This can be remedied by studying serial exams in future studies. While PEC and control patients were matched by gestational age, there may likely be other systematic differences between the groups that could confound the results. Furthermore, due to the lack of 3D capability in our echocardiography instrument at the time of the study, we were unable to measure 3D volumetric LV EF, which is known to be a more accurate echocardiographic modality for the measurement of LV EF . FurtherIt has to be emphasized that echocardiographic indices of PAH are only estimations and they are used to raise the probability of PAH rather than to establish a conclusive PAH diagnosis.The noninvasive assessment of PA hemodynamics and RV function by echocardiography may have utility in assessing the cardiovascular status of PEC patients. Our findings suggest that there is an increase in eMPAP and ePVR in PEC, particularly in early-onset cases. There is also evidence of a parallel mild decrement of RV structure and function. The data we obtained is preliminary, and we recommend that an adequately powered longitudinal study be conducted to assess the clinical significance of our findings, their association with maternal and fetal outcomes, and the condition's responsiveness to antihypertensive therapies.


Persistent minor troponin elevation in patients with coronary heart disease is associated with adverse outcome and prognosis. However, the mechanism is not yet clearly understood.Our objectives were to examine the prevalence and range of cardiac troponin T (cTnT) in stable patients six months after acute myocardial infarction (AMI) using a new high sensitive cTnT assay and to investigate the association of persistent minor cTnT-elevation to clinical variables, NT-pro BNP and cardiac MR-findings.cTnT was measured in 98 patients at 6 months after AMI. Patients were investigated in a clinical 1.5 Tesla whole body MR-scanner  3 ± 1 days after successful mechanical reperfusion of the infarct related vessel and at a follow-up of 6 ± 1 month using a 5-element phased array cardiac synergy coil.Assessment of resting left ventricular function was determined by cine images using a steady-state-free precession sequence in 10–12 8 mm-thick slices covering the whole left ventricle from base to apex as well as long axis 2,-3 and 4-chamber views.®, Bayer, Germany)) late enhancement-imaging was performed using an inversion-recovery gradient-echo technique triggered to end-diastole. Data analysis of MRI-images was performed using a usual Philips work station.Ten minutes after gadolinium contrast injection . These patients were also significantly older, suffered more frequently from hypertension, had a higher New York Heart Association class and received more often diuretics at follow-up. Patients with cTnT-elevation had a more impaired left ventricular ejection fraction (p = 0.02) but did not have an increased infarct size (p = 0.73).Minor cTnT-concentrations were detectable in 90% of the entire cohort, of whom 16% had cTnT-values above the 99Elevated minor cTnT levels are frequently detectable in patients 6 month after AMI. Increased cTnT-level were associated with clinical parameter for heart failure, impaired ejection fraction and higher NT-pro-BNP levels suggesting that myocardial dysfunction leads to persistent cTnT-elevation.


In acute ST-segment elevation myocardial infarction (STEMI), successful restoration of blood flow in the infarct-related coronary artery may not secure effective myocardial reperfusion. The mortality and morbidity associated with acute MI remain significant. Microvascular obstruction (MVO) represents failed microvascular reperfusion. MVO is under-recognized, independently associated with adverse cardiac prognosis and represents an unmet therapeutic need.Multiple factors including clinical presentation, patient characteristics, biochemical markers, and imaging parameters are associated with MVO after MI.Impaired microvascular reperfusion is common following percutaneous coronary intervention (PCI). New knowledge about disease mechanisms underpins precision medicine with individualized risk assessment, investigation, and stratified therapy. To date, there are no evidence-based therapies to prevent or treat MVO post-MI. Identifying novel therapy for MVO is the next frontier. Acute ST-segment elevation myocardial infarction (STEMI) is a major cause of premature death and morbidity . RestoraMicrovascular reperfusion is the ability to perfuse the coronary microcirculation in a previously ischemic region after opening the epicardial vessel. Successful restoration of epicardial blood flow does not guarantee myocardial reperfusion. There is evidence of impaired microvascular perfusion on cardiac magnetic resonance (CMR) imaging in over half of patients following STEMI despite angiographic patency of the infarct-related artery post-PCI . This acIn clinical practice, MVO is likely to pass undetected in many cases. The limits of contemporary coronary revascularization in known myocardial ischemia have been highlighted in the recent ISCHEMIA trial . The focIn this review, we consider the definition of microvascular reperfusion after MI on a practical basis in a range of clinical settings throughout the patient journey. We provide an overview of the predictors of coronary microvascular dysfunction in this context and address the concept of stratified medicine in the future.Coronary microvasculature holds 20% of myocardial blood volume and modulates myocardial perfusion , 12. ImpThe evolution of microvascular reperfusion after MI is relevant when considering assessment methods used to define it. Experimental models indicate that myocardial perfusion defects occur during the process of reperfusion . RadioloCoronary microvascular dysfunction runs a dynamic temporal course following reperfusion in acute MI. The definition of microvascular reperfusion is dependent on method of detection and also the time point at which assessment takes place. Impaired microvascular reperfusion defined using different methods is prognostically important •, 22.MVO occurs following reperfusion in both STEMI and non-ST-elevation acute myocardial infarction (NSTEMI). NSTEMI is a heterogeneous condition with a variable clinical course that typically exhibits a relapsing and remitting myocardial ischemia that is less clamant than is the case for STEMI. Rates of MVO following early revascularization in NSTEMI are lower , 24 but The test options for assessing reperfusion injury differ according to the time-point and location in the patient care pathway Fig. .Fig. 1MaThe thrombolysis in myocardial infarction (TIMI) flow grading system is a widely used visual assessment of flow appearance that provides an immediate evaluation of microvascular reperfusion . CompletMethods such as myocardial blush grading (MBG) and fluoroscopy assisted scoring have been introduced to enhance visual assessment and reduce operator variability , 32. MBGThe spatial resolution of coronary angiography is approximately tenfold larger than the diameter of arterioles that govern myocardial blood flow . Visual An intracoronary unipolar electrocardiogram can be acquired while in the catheterization laboratory by connecting the proximal end of the angioplasty guidewire to a monitor using a crocodile clip . IC-ECG Coronary physiology measurements using diagnostic guidewire sensors have emerged as useful tools in the diagnosis and management of disorders of coronary function . These mIMR represents the minimum microvascular resistance during adenosine-induced hyperemia and is a validated measure of microcirculatory reperfusion •, 42. LoHMR is calculated by dividing distal coronary pressure by mean Doppler flow velocity at peak hyperemia. In keeping with IMR, low values indicate successful microvascular reperfusion whereas raised values (≥ 2.5) are suggestive of MVO . Predictand microcirculatory vasodilator capacity and can be derived utilizing Doppler or thermodilution techniques [CFR reflects epicardial chniques . High CFchniques . CFR is RRR is a measure of the difference between basal resting tone in the microcirculation and resistance at maximal hyperemia and reflects the ability of the coronary microcirculation to vary resistance to hyperemic stimuli. Elevated values indicate increased vasodilator capacity and thus successful microvascular reperfusion. Reduced RRR (≤ 1.7) is associated with the presence and extent of MVO, albeit to a lesser extent than IMR when using dichotomized values •, 49, 50TRT is the time taken for the temperature at the guidewire tip to return to baseline during maximal hyperemia. Low TRT indicates successful microcirculatory reperfusion. Recent research demonstrates correlation between MVO and longer recovery time (TRT ≥ 0.5) with similar predictive accuracy to IMR .p = 0.01) [During mid-diastole, a linear relationship exists between pressure and flow. Coronary zero flow pressure (PZF) is an index derived from the extrapolation of coronary pressure-flow velocity loops . Theoret = 0.01) . PZF is  = 0.01) , 54.Echocardiography is a standard care assessment in patients following an acute MI. Reduced ejection fraction carries prognostic significance and is more common in populations with MVO , 55. RegThe coronary flow-velocity ratio (CFVR) is derived from diastolic flow measurements in epicardial coronary arteries during rest/stress using Doppler echocardiography. In the absence of epicardial flow limitation, CFVR > 2.5 indicates normal microvascular function , 56. To Regional myocardial ischemia results in edema (increased water content) and prolongs longitudinal (T1) and transverse (T2) relaxation times increasing regional signal intensity on CMR images . MVO is Contrast-enhanced CMR is considered the gold-standard in vivo assessment of MVO and is the reference diagnostic test in trials that have uncovered the prognostic implications of impaired microvascular reperfusion following MI •, 64. CMDelayed contrast-enhanced CT has potential for tissue characterization; however, unlike CMR, CT is limited by image quality and radiation exposure .Nuclear imaging is frequently used to assess myocardial blood flow, and positron emission tomography (PET) is a validated means of coronary vasomotor function testing. Myocardial scintigraphy can detect capillary reperfusion defects following coronary thrombolysis . The rolWell-recognize factors linked to adverse cardiac prognosis may confer their detrimental effects via microvascular obstruction. Underlying health conditions, clinical presentation features, ECG parameters, and laboratory results have a role in predicting the likelihood of successful microvascular reperfusion after MI Fig. . MicrovaCardiovascular risk factors are common in patients presenting with STEMI. Comorbid conditions, such as hypertension and diabetes, are associated with endothelial dysfunction  and coulDiabetes has established multisystemic macro- and microvascular complications. The condition increases the probability of a cardiovascular event and worsens prognosis thereafter . Hyperglp = 0.006) [Large studies have been unable to demonstrate convincing association between pre-existing diabetes and MVO following re-perfused STEMI. There does however appears to be a link between hyperglycemia at presentation and subsequent microvascular dysfunction following PCI , 73. In = 0.006) . This re= 0.006) . To date= 0.006) , 77.Obesity (defined by raised body mass index) has not been shown to demonstrate significant correlation with microvascular perfusion defects post-STEMI , 78.Hypertension is associated with endothelial dysfunction and is a strong negative prognostic indicator after STEMI –81. Howep = 0.002) [Hypercholesterolemia is associated with coronary heart disease and cholesterol-lowering therapy conveys mortality benefit in this cohort . A degre= 0.002) . Other c= 0.002) , 88.improved microvascular perfusion defined by coronary physiology and ECG parameters in the acute phase after reperfusion in smokers, followed by subsequent development of microvascular injury. Ultimately, when adjusted for infarct size, cigarette smoking was identified as an independent predictor for IMH  but not MVO [Cigarette smoking negatively impacts coronary endothelial function and increases the risk of developing cardiovascular disease , 90. The not MVO .younger patients [Elderly STEMI patients who have undergone revascularization are more likely to demonstrate impaired microvascular reperfusion defined by ECG STR and angiographic TIMI grade , 95–97. patients . These fFemales presenting with STEMI, especially when under the age of 60, have a higher mortality rate than males –100. ThiSTEMI predominately affects men who present at a younger age with a first MI than is the case for women. This fact highlights natural sex differences in the epidemiology of ischemic heart disease.Genetic variants contribute to an individual’s risk of coronary artery disease and single-nucleotide polymorphisms have been identified within certain genes  that correlate with microvascular dysfunction , 105. Rep = 0.02). Other studies report correlation between residual STE and MVO at 48–72 h [The 12-lead ECG is the standard-of-care diagnostic assessment in myocardial infarction. The extent of STR has been used as measure of epicardial reperfusion dating back to the era of cardiac thrombolysis. Variations of this approach now form part of contemporary assessment of microvascular dysfunction after revascularized STEMI where complete STR indicates successful microcirculatory reperfusion and failed STR (< 30% resolution) or persistent ST-elevation (STE) despite adequate flow appearance is attributed to MVO. ST-elevation is greater in individuals with MVO before and after coronary intervention . There a 48–72 h , 109.p = 0.003) [p = 0.024) and predictive value for MVO  [QRS duration on presentation has been shown to be independently associated with angiographic no-reflow  . The Sel= 0.003) . It is a= 0.001) , 113. Th= 0.001) , 114.p = < 0.0001) [Reducing “door-to-balloon” time improves mortality in STEMI . Treatme 0.0001) •. This i 0.0001) , 93, 96.The development of MVO is associated with larger infarct size, anterior infarct location, and reduced initial TIMI grade , 9•. Indp = 0.027) [Killip class (extent of heart failure at presentation with MI) is significantly linked with MVO across a range of assessment methods , 93, 97.= 0.027) , 118, an= 0.027) , or remo= 0.027) .p = <0.001 vs. AUC 0.64, 95% CI 0.56–0.72; p = 0.001) [Plasma levels of cardiac troponin are associated with the presence and extent of MVO following re-perfused STEMI. Various cut-off values have been proposed that demonstrate high predictive accuracy, particularly if using peak levels –125. Pea= 0.001)  and cons= 0.001) .Elevated circulating N-terminal pro-brain natriuretic peptide (NTpro-BNP) also demonstrates association with MVO in this population . In a 20p = <0.05). Although peak values where more prognostically useful, sensitivity and specificity for MVO did not exceed 80% [Other biomarkers that have demonstrated association with the development of MVO post re-perfused STEMI include creatinine kinase (CK), high-sensitivity C-reactive protein (hsCRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)—suggesting a possible link to inflammatory conditions. Mayr et al. demonstrated significantly elevated CK, hsCRP, and LDH within the first 4 days following PCI in those later confirmed to have MVO. These markers all correlated with MVO size . A CMR fceed 80% .n = 44, p = < 0.001). Predictive value was superior to residual STE or angiographic parameters and similar to peak troponin levels [An evolving understanding of factors that are associated with MVO after MI has led to the development of predictive scoring systems. Husser et al. compared clinical parameters, ECG, biomarker, and angiographic data in the prediction of impaired microvascular reperfusion following STEMI. Their score includes Killip class (double weighting), age < 55, diabetes, time to reperfusion, and sum STE. Incidence of MVO increased with each score increment and is reported as 93% for scores ≥ 3 (n levels .p = <0.001) [2DS2-VASc score is a widely used predictor of thromboembolic events in atrial fibrillation. When applied retrospectively to a STEMI population, it has also been shown to have predictive value for angiographic no-reflow  [Pre-existing scoring systems have been applied to the assessment of microvascular dysfunction after acute MI. The SYNTAX score uses a combination of coronary characteristics from angiography. Magro et al. demonstrated the utility of this scoring system as an independent predictor of angiographic no-reflow in 669 patients after revascularized STEMI  , 128. Th< 0.001) , 130.p = < 0.001) [p = 0.03) and demonstrated a graded increase dependent on the extent of MVO as a percentage of left ventricular myocardial mass [Coronary microvascular disease is not benign. Impaired microvascular reperfusion joins established markers of adverse cardiac prognosis such as infarct size . In a me< 0.001) . This isial mass •.The significance of MVO in patients with acute MI has spurred research in recent years into the investigation of adjunctive therapies that aim to modify MVO and improve outcomes. Potential interventions include intracoronary drug delivery (fibrinolytics and vasodilator therapy), deferred coronary stenting, ischemic conditioning, parenteral beta-blockade, and antiplatelets among other pharmacotherapies. To date, major trial data relating to these methods has largely failed to demonstrate consistent improvements to either markers of microvascular reperfusion or MACE.The METOCARD-CNIC randomized control trial investigated the effect of intravenous metoprolol administered prior to reperfusion in anterior STEMI with Killip class ≤ 2. Metoprolol use was associated with a 40% reduction in the extent of MVO on CMR at 1 week. This remained significant even when adjusted for infarct size and other confounding factors. Infarct size and left-ventricular ejection fraction were improved at 6 months in the metoprolol group but incidence of MACE at 2 years was comparable , 133. PrStudies are underway that are investigating the impact of novel interventions including pressure-controlled intermittent coronary sinus occlusion (NCT03625869), localized intracoronary hypothermia (NCT03447834), selective strategies to defer stenting (NCT01542385) , and outThe mortality and morbidity associated with acute MI remain significant. Impaired microvascular reperfusion is a common complication following coronary intervention in this condition. This is defined as MVO and can be detected at different time-points across a range of modalities. MVO is under-recognized, independently associated with adverse cardiac prognosis, and represents an unmet therapeutic need.A range of factors have emerged that correlate with MVO after MI. An enhanced understanding of these predictive factors forms the foundation for a move towards precision medicine with individualized risk assessment, investigation, and subsequent stratified therapy with novel treatments. The successful modification of this process represents the next therapeutic frontier.


Identification of regional myocardial dysfunction with adequate temporal and spatial resolution is important for diagnosis and management of cardiovascular disease. Assessment of regional myocardial velocities allows 3-dimensional quantification of left ventricular function and carries independent prognostic information.The aim of this study was to use navigator gated tissue phase mapping with high temporal resolution to obtain accurate normative data of left ventricular velocities, to assess normal patterns of left ventricular motion and to evaluate the reproducibility of this technique.Cardiac magnetic resonance examinations were performed on a 1.5 Tesla MR clinical scanner . Cardiac gated, phase contrast measurements using respiratory navigator with a temporal resolution of 13.8 ms were obtained on two separate occasions on 13 healthy male subjects (age 22 ± 3 years) three weeks apart. Three short axis images were obtained for the left ventricular base, mid-ventricle and apex. Each short axis acquisition took approximately 3 – 5 minutes, with an average of 60 – 70 phases per cardiac cycle. Subsequent normative velocities were obtained for radial, circumferential and longitudinal motion.High temporal resolution tissue phase mapping analysis allowed visualization of additional details of ventricular motion that have not been observed with breath-held lower temporal resolution tissue phase mapping . ChangesNavigator gated tissue phase mapping with high temporal resolution is a reproducible technique to evaluate detailed regional myocardial wall motion and provides valuable and comprehensive information for quantifying myocardial velocities. The technique allowed us to obtain new details of left ventricular motion patterns and may prove to be a powerful tool for assessing subtle changes in myocardial function in cardiac disease.


Design Prospective cohort study with a 30-d follow-up from an index consultation. Regression models to determine independent factors associated with hospitalisation or death. To evaluate the precipitating factors for heart failure decompensation in primary care and associations with short-term prognosis. Patients Patients with diagnosis of heart failure attended in primary care for a heart failure decompensation . Primary care in ten European countries.  Potential precipitating factors for decompensation of heart failure and their association with the event of hospitalisation or mortality 30 d after a decompensation. Of 692 patients 54% were women, mean age 81 (standard deviation [SD] 8.9) years; mean left ventricular ejection fraction (LVEF) 55% (SD 12%). Most frequently identified heart failure precipitation factors were respiratory infections in 194 patients (28%), non-compliance of dietary recommendations in 184 (27%) and non-compliance with pharmacological treatment in 157 (23%). The two strongest precipitating factors to predict 30 d hospitalisation or death were respiratory infections ) and atrial fibrillation (AF) > 110 beats/min . Multivariate analysis confirmed the association between the following variables and hospitalisation/death: In relation to precipitating factors: respiratory infection  and AF with heart rate > 110 beats/min ; and regarding patient characteristics: New York Heart Association (NYHA) III or IV ; previous hospitalisation ; and LVEF < 40% .Hospitalisation due to heart failure decompensation represents the highest share of healthcare costs for this disease.So far, no primary care studies have analysed the relationship between precipitating factors and short term prognosis of heart failure decompensation episodes.We found that in 692 patients with heart failure decompensation in primary care, the respiratory infection and rapid atrial fibrillation (AF) increased the risk of short-term hospital admission or death.Patients with a hospital admission the previous year and a decompensation episode caused by respiratory infection were even more likely to be hospitalized or die within 30 d. In primary care, respiratory infections and rapid AF are the most important precipitating factors for hospitalisation and death within 30 d following an episode of heart failure decompensation. Heart failure is a chronic disease that affects approximately 1–2% of the population . Heart fThe objective of this study was, therefore, to identify the most frequent decompensation precipitating factors and analyse their association with short-term prognosis defined as hospitalisation/death within 30 d from an index consultation date.The HEFESTOS is an international prospective cohort study focused on identifying the precipitating factors involved in heart failure decompensation in primary care. In addition, it aims to create a predictive prognostic model in heart failure patients suffering from a decompensation episode.The study was originally designed in Spain where a pilot study was carried out to test feasibility. Initially, 30 patients who had presented 13 events in one primary healthcare centre were recruited.The protocol was presented in a meeting of the European General Practice Research Network where family doctors from nine countries agreed to collaborate. The European investigators then gathered in order to standardise the methodological procedures and extend the study to different countries. The study protocol was written in English with funding for translations to other languages.Patients registered as having heart failure (according to the European Society of Cardiology criteria)  and atteData on the following were collected: age, sex and comorbidity including hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, permanent atrial fibrillation (AF), chronic renal failure and stroke. New York Heart Association (NYHA) functional class, time from commencement of symptoms until primary care consultation, hospitalisation due to heart failure in the year prior to decompensation, left ventricular ejection fraction (LVEF) and precipitating factors were also assessed.Dietary transgression: if the patient reported liquid intake of more than 2.5 l a day and/or added salt to the food.Respiratory infection. Diagnosis was made by clinical exploration and confirmed in the medical records.Non-compliance with pharmacological treatment (self-reported).AF with a frequency > 110 beats per minute (bpm) requiring treatment or emergency referral.Other infections: signs and symptoms of infections other than respiratory ones.Cardiac ischemia: clinical and electrocardiographic signs of ischaemia that required changes in treatment or emergency referral.Intake of drugs associated with heart failure decompensation: non-steroidal anti-inflammatory drugs, effervescent tablets, corticosteroids, tricyclic antidepressants.Other precipitants: anaemia, worsening of renal function, hypertensive crisis, changes in diuretic treatment.The following precipitating factors were taken into consideration if they appeared concomitantly with decompensation:The primary outcomes were hospitalisation due to cardiovascular causes and/or mortality from any cause in the 30 d following the index consultation date. They were verified through consulting medical records and/or by phone.p < .05) associated with the primary outcome in the bivariate analysis were included as potential covariates in logistic regression models. Analyses were performed using R project version 3.6.0  [Categorical data are expressed using frequencies and percentages, while continuous data are expressed using means and standard deviations (SD). A chi-square test was used to compare data when it was categorical. A Student’s t-test was used for independent groups. Binary logistic regression analyses were used to investigate the effect of the characteristics of patients and precipitating factors in the primary outcome. Variables significantly (Austria) .Between August 2015 and December 2018, a total of 692 patients from ten countries were included. Women represented 55% of the participants and mean age was 81.2 (SD 8.90) years. Mean LVEF was 55% (SD 12%). The average time between consultation and onset of symptoms was 9.1 d (SD 9.1).Among the 692 patients evaluated, 195 (28%) were hospitalised and 24 (3.5%) died during the first month following the decompensation episode. At least one precipitating factor was identified in 156 (78%) of the 200 events, only one in 84 events (42%), two in 45 events (22%) and three or more in 27 events (14%). The most frequently identified precipitating factors were: respiratory infection (28%), transgression of dietary recommendations (27%) and non-compliance with pharmacological treatment (23%). In univariate analysis, patients suffering from a respiratory infection, or AF with a heart rate >110 beats/min, had a significantly higher probability of hospitalisation/death  and , respectively. In contrast, patients with dietary transgression had a lower probability of hospitalisation/death . Regardless of the characteristics of patients; patients hospitalised during the previous year, presenting a history of diabetes mellitus, chronic obstructive pulmonary disease (COPD), hypercholesterolemia, LVEF < 40% or functional stage NYHA III or IV, treatment with ACE/or aldosterone antagonist had a higher probability of hospitalisation/death in the first 30 d following the episode .A multivariate analysis including underlying patient characteristics confirmed the association between the following variables and hospitalisation/death. With respect to precipitating factors: respiratory infection  and AF with heart rate >110 beats/min ; and in relation to patient characteristics: NYHA III or IV ; previous hospitalisation ; and LVEF < 40%  .These variables, with and without hospitalisation for heart failure the year before the consultation, were analysed separately, including interactions in the multivariate model. It was observed that hospitalisation in the previous year due to heart failure interacted with respiratory infection and dietary transgression. The probability of hospitalisation/death from an episode precipitated by respiratory infection was much greater if there had been a previous hospitalisation  than if there had not . Dietary transgression reduced the probability of an adverse event, although only in those who had not been previously hospitalised  .Among the 692 patients from ten European countries presenting an episode of heart failure decompensation in primary care, in more than three out of four cases at least one precipitating factor was identified, the most frequent being respiratory infection. In addition, respiratory infection and rapid AF were associated with a high probability hospitalisation/death within 30 d which occurred in 29% of the decompensation episodes.A major strength of this study is its prospective cohort design and international perspective (patients were recruited from ten European countries). A selection bias, however, could have occurred since the more severely ill subjects might have been identified. Nevertheless, the primary care physicians responsible for recruitment were instructed to consecutively include any patient with decompensated heart failure. Due to the low percentage of patients who died we could not analyse hospitalisation and death separately, consequently the main outcome was a combination of both.Some studies  have shoA major limitation is not having determined the natriuretic peptides due to their low availability in primary care; even though NT-proBNP has a prognostic value in heart failure patients with an ejection fraction ≥ 40%. Clinical use is, however, limited as a result of large SDs, many co-morbidities and greater age .To the best of our knowledge, this is the first study to analyse the role of precipitating factors in heart failure decompensation in primary care. Compared to previous similar studies, there was a greater proportion of women, higher comorbidity and a larger percentage presenting preserved ejection fraction which we attribute to the higher average age of our population ,14,16–23The percentage of patients with a precipitating factor is within the range described by other authors (between 60 and 98%) ,22,23. WThe role of respiratory infection in heart failure decompensation has also been identified mainly in studies undertaken in hospital emergency rooms and internal medicine units ,17–19,25We detected that the probability of hospitalisation/death after a respiratory infection was even greater when patients had been admitted to hospital in the previous year, which is consistent with other authors . Such fiDietary transgression has also been commonly described as a precipitating factor for heart failure decompensation . Non-comAF is also often related to heart failure decompensation ,17,21. FIn our study, we considered the use of non-indicated/contraindicated medications as a possible cause of decompensation, an issue which was not mentioned in the Standardised reporting criteria .Only a few studies have analysed the role of precipitating factors in the prognosis of heart failure ,10,22,23Regarding comorbidity and decompensation short-term prognosis, in the univariate analysis the presence of diabetes mellitus and COPD was related to a greater probability of admission/death. This relationship however, was lost when performing the multivariate analysis. The presence of these two conditions has been related to the long-term prognosis of heart failure, particularly with ejection fraction , neverthOne of the most striking findings of the study was that patients in whom dietary transgression had been identified had a lower probability of being hospitalised or dying. A lower probability that was not observed in those who had been hospitalised for heart failure in the previous year. A number of studies have reported that a dietary sodium restriction < 2 g/d provides benefits only in more advanced stages, and is neutral or even harmful in milder stages which could partly explain our results . AnotherIn a primary care study from 10 European countries, we identified respiratory infections and rapid AF as the most important precipitating factors for hospitalisation and death within 30 d following an episode of heart failure decompensation.Patients with a hospital admission the previous year, and a decompensation episode caused by respiratory infection, were even more likely to be hospitalised or die within 30 d.


Background: This study was designed to assess right ventricular systolic function in cancer patients. Methods and Results: 68 consecutive patients receiving potentially cardiotoxic agents were followed for 6 months in a single-center, observational, cohort-study. Left ventricle and free-wall right ventricular longitudinal strain were analyzed prior and after 6 months of treatment, using a vendor-independent software, together with left ventricle ejection fraction, tricuspid annulus plane systolic excursion and right ventricular fractional area change. Cancer therapy-related cardiac dysfunction was defined as a left ventricle ejection fraction drop of >10% to <53%. Both left ventricle ejection fraction  and left ventricle longitudinal strain  were reduced at follow up, along with free-wall right ventricular longitudinal strain . Cancer therapy-related cardiac dysfunction was detected in 20 patients (29%). In 15 out of these 20 patients (75%), a concomitant relative reduction in free-wall right ventricular longitudinal strain magnitude by 17±7% was detected. Moreover, there was a significant correlation between left ventricle and free-wall right ventricular longitudinal strain at follow-up examinations . A relative drop of right ventricular longitudinal strain >17% had a sensitivity of 55% and a specificity of 70%  to identify patients with cancer treatment related cardiac dysfunction. Neither tricuspid annulus plane systolic excursion , nor right ventricular fractional area change  showed any significant change between examinations.Conclusions: Longitudinal strain analysis allows the identification of subclinical right ventricular dysfunction appearing in the course of cancer treatment when conventional indices of right ventricular dysfunction function are unaffected. Further characterization of CTRCD relies on presence/absence of symptoms and reversibility.Cancer therapy-related cardiac dysfunction (CTRCD) diagnosis is conventionally based on the measurement of left ventricular ejection fraction (LVEF), using various cardiac imaging modalities. According to current recommendations, a LVEF decrease of more than 10% to a value of less than 53%, assessed by two-dimensional echocardiography (2DE), using the biplane Simpson’s method and demonstrated by repeated studies defines CTRCD2.Induced cardiotoxicity expressed through CTRCD is most likely a continuous phenomenon characterized by progressive decline in LVEF. Because LVEF decreases when a critical amount of myocardial damage has occurred and cardiac compensatory mechanisms are exhausted, many affected patients may initially be asymptomatic, with clinical manifestations appearing even years later, often in the context of other triggering factors3. Furthermore, if CTRCD is detected early, patients frequently have a good functional recovery. Conversely, if patients are identified late after the onset of cardiac dysfunction, heart failure (HF) is typically more difficult to treat4.Thus, detection of subclinical cardiac abnormalities, which may influence clinical decisions regarding the choice of chemotherapy, indication for cardioprotection or increased surveillance frequency (e.g. asymptomatic LV dysfunction) is crucial for cancer patients undergoing potential cardiotoxic regimesBecause LVEF measurement is a relatively insensitive tool for detecting early CTRCD, increasing efforts have been carried out in demonstrating the value of deformation imaging or strain for subclinical CTRCD detection. Myocardial deformation imaging performed using either Tissue Doppler Imaging (TDI) or speckle tracking echocardiography (STE) techniques allows the evaluation of LV and right ventricle (RV) myocardial mechanics.5 and currently LVGLS represents a criterion for CTRCD diagnosis2: a relative reduction of more than 15% from baseline LVGLS suggests the risk of cardiotoxicity and further CTRCD.LV global longitudinal strain (LVGLS) seems to be the most reproducible and useful deformation parameter in predicting subsequent CTRCD and HF before becoming clinically manifested6-11, and likewise, the clinical and prognostic value of RV strain analysis was demonstrated so far in patients with pulmonary hypertension, heart failure and LV assist devices, congenital heart diseases, storage diseases and cardiomyopathies with high risk of malignant ventricular arrhythmias6-8.On the other hand, RV function and mechanics have proven to be important indicators of overall cardiovascular morbidity and mortality1,3, RV free wall strain (RVFWLS) has been recommended as a more sensitive index of RV systolic dysfunction, being less load dependent and less influenced by heart motion than conventional parameters11.Although RV systolic function assessment through conventional parameters is recommended by the European and American expert consensus regarding cardiac function monitoring during cancer treatmentHowever, the presence and the extent of RV function impairment during cancer therapy has not been adequately studied. Accordingly, this study was designed to assess RV systolic function in patients undergoing potential cardiotoxic treatments by longitudinal strain analysis and conventional parameters, using a vendor-independent, cardio-oncology dedicated software.Consecutive patients receiving potentially cardiotoxic agents and undergoing clinically indicated echocardiography studies for CTRCD monitoring, before and after 6 months of treatment, as main indication, were enrolled in asingle-center, observational cohort-study.Patients were selected for acceptable image quality, excluding patients with two or more segments not visualized by conventional 2DE. Other exclusion criteria included severely dilated LV and LVEF less than 53% at baseline examination. For each patient the following data were obtained: patient demographics, cardiac risk factors and previous cardiac and malignancy history. All patients gave their informed consent in agreement with the local Ethics Committee.11, four-, three-, and two- chambers apical LV views for LVGLS analysis and LVEF calculation were recorded, along with RV-focused apical four-chambers view for RV free wall longitudinal strain (RVFWLS) analysis and RV fractional area change (RVFAC) calculation. Additionally, tricuspid annulus plane systolic excursion (TAPSE) was measured using an M-mode cursor passed through the tricuspid lateral annulus.Complete 2DE studies were performed prior and 6 months after receiving potential cardiotoxic treatment by experienced sonographers using commercially available ultrasound machines: Vivid E9  and Philips IE33 (Philips Ultrasound) equipped with M5S probe and X5-1, respectively. In according to current guidelinesAll patients were examined in the left lateral position using grey-scale second-harmonic 2D imaging technique, with the adjustment of image contrast, frequency, depth, and sector size for adequate frame rate (50-80 fps) and optimal LV and RV border visualization. Care was taken to avoid LV and RV foreshortening, and image acquisition was done during breath-hold to minimize respiratory movements. Data sets were digitally stored in DICOM  images-data format and exported to a separate workstation for offline analysis.. The method was applied independently in all patients and in random order, on digitally stored DICOM images-data format, by the same observer (D.A.C.), blinded to the clinical data.A semi-automated vendor-independent software  was used to load simultaneous baseline and follow up studies Briefly, after the end-diastole and end-systole of the LV apical four-, three- and two-chambers views frames were identified using frame-by-frame analysis and based on mitral valve closure and electrocardiogram (ECG) trace, endocardial boundary was traced manually, using an interrupted mouse clicks technique and tracked throughout the cardiac cycle based on an automated STE algorithm, resulting in LV volumes and peak systolic LVGLS over time. LVGLS and LVEF were automatically calculated by the software for both baseline and follow up studies, as following: LVGLS as the mean peak systolic strain value measured in all 2D points in the three apical views (18-segments model) and LVEF as the corresponding end-systolic and end-diastolic volumes in four-and two- chambers LV views, using biplane disc-summation algorithm (modified Simpson’s rule).. This approach was preferred to RVGLS, because it is based on the inclusion of the interventricular septum that may partially reflect changes in the LV, as the septum is shared by both ventricles11.RV analysis was performed for baseline and 6 months follow up studies for each patient, using the same automated STE algorithm as for LV. First, tracing of the entire RV endocardial border in RV-focused apical four-chamber view was performed, obtaining RV global longitudinal strain (RVGLS) (including the septum) strain value. Then, RVFWLS was computed by averaging the peak systolic strain values of the three segments of the free wall (from base to apex), displayed by the software RVFAC was automatically calculated after manually tracing RV endocardial border after end-diastole and end-systole frames were identified, paying attention to include the trabeculated endocardium within the RV cavity.Using the tricuspid lateral annulus M mode RV focused four-chamber view, TAPSE was manually traced, as the distance between end-diastole and peak systole excursion of the RV annular plane towards the apex.. Changes between baseline and follow-up studies in LVEF, LVGLS, RVFWLS, RVFAC and TAPSE – noted with the sign Δ, were automatically reported in proportions of the original value. E.g. a change in LVGLS value from −20% to −10% was reported as ΔLVGLS = 50%.Finally, the software then generated an integrated display of changes in LVEF and LVGLS from baseline to follow-up Variables are expressed as mean ± standard deviation (SD). Contingency tables were applied to characterize the demographic and clinical profile of the study group. Pearson test was used to investigate the correlation power between variables. The normal distribution was measured univariate (one by one), using Kolmogorov Smirnov test. Homoscedasticity, as the multivariate normality, was checked with a M-Box test, for a p < 0.05.We used stepwise Discriminant Analysis (DA) to set the predictive power of the variables for CTRCD. DA was preferred to Logistic Regression because it is a more solid and robust analysis for small samples size. Assumptions were made by differentiating patients in three groups: (1) LVEF drop with > 10% to < 53%, (2) RVFWLS > −20% (< 20% in magnitude with the negative sign) from group (1), and (3) patients with no CTRCD. The differences of variables in each group were investigated in first place, by the ANOVA test. A p value < 0.05 was considered statistically significant. Firstly, the DA found the most important classificatory factors (most predictive variables using ANOVA test). Secondly, the DA identified the discriminating functions that can explain the variability of the groups, discovering which one is more important in each function. Finally, DA checked the predictive power of the functions, and assigned the probability to predict individually enclosure to one or another group. The independent variables that were classified by DA are important predictors for CTRCD.Receiver operating characteristic (ROC) analysis was used to display results about the sensibility and specificity of the studied variables to predict CTRCD.Data were analyzed using SPSS version 22.0 .A total of 155 patients were addressed for an echocardiography study for CTRCD monitoring between October 2014 and August 2016 at the echocardiography laboratory of the Department of Cardiology, Emergency County Hospital, Craiova, Romania. Among these patients, 107 (69%) had at least one follow-up examination after 6 months and only 68 (43%) met our inclusion criteria. The remaining patients were either not sent for follow up examinations by the treating hematologist/oncologist, had an echocardiography study with poor image quality, had LVEF < 53% or were followed by other Cardiology centers.Table 1. 90% of CTRCD group patients (n = 18) were treated with anthracycline-based scheme: doxorubicin and cyclophosphamide followed by either bleomycin or vincristine and monoclonal antibody-rituximab: R-CHOP, R-FCM, R-BEACOP schemes, while only 10% of patients (n = 2) were treated with bortezomib, melphalan and corticosteroids (VMP scheme).68 patients from Hematology and Oncology departments were followed for 6 months. Demographics, clinical characteristics and malignancy history of the study patients’ group are described in All study patients (n = 68) had normal pre-chemotherapy LVEF values. .Both LVEF  and LVGLS  were reduced at follow up. RVFWLS also decreased in magnitude . Neither TAPSE , nor RVFAC  showed any significant change between baseline and follow-up examinations1, a study sub-group resulted: patients with LVEF drop of > 10% to a value of < 53%  or CTRCD patients’ group .Taking into consideration the cut-off value for CTRCD definition7.LVEF was significantly reduced to 46 ± 7.5% in CTRCD patients’ group, compared to pre-treatment mean values of 58 ± 8% (p < 0.0001). LVGLS was abnormal during CTRCD, decreasing to −14 ± 2% versus −18 ± 2% (p < 0.0001), being significantly lower than the published lower limit of normal value for LVGLS of > −18 % (< 18 with the negative sign)Changes between baseline and follow-up studies: ΔLVEF, ΔLVGLS, ΔRVFWLS, ΔRVFAC and ΔTAPSE, were automatically reported in proportions of the original value.1,2.ΔLVGLS decreased by 20 ± 7%, being even higher than the reported abnormal limit of 15% change from baseline to follow-up LVGLS, significant enough to predict subclinical CTRCD11, an abnormality threshold for the RVFWLS was set at > −20% (< 20% in magnitude with the negative sign)11, resulting that 15 out of 20 patients experiencing CTRCD (75%) in our study had RVFWLS abnormal values. Interestingly, among these patients, RV dysfunction evaluated by conventional parameters was present in only 5 patients by RVFAC, while by TAPSE reduction in only 3 patients.In the most up-to-date version of the cardiac chamber quantification guidelines for echocardiography11. The same scenario was noted for TAPSE  for < 17 mm as lower limit of normal value11.RVFWLS was significantly decreased compared to baseline  during CTRCD and ΔRVFWLS was 17 ± 7%. RVFAC was significantly lower at follow-up for CTRCD patients , although still in the normal range Moreover, significant correlation resulted between follow-up RVFWLS and LVGLS , RVFWLS and LVEF  and RVFWLS and female gender .Stepwise DA found that next to ΔLVEF, ΔRVFWLS is an important factor for predicting CTRCD, meaning that ΔLVEF by itself is not enough to explain the differences between groups. The probabilities of classification of those functions obtained with DA are approximately 97% for individual classifying. established that a relative drop of RVFWLS > 17% had a sensitivity of 55% and a specificity of 70%  to identify patients with CTRCD.The ROC curve for CTRCD group At the time of CTRCD, 2 patients (10%) reported symptoms consistent with class II-III New York Heart Association (NYHA) HF and had severely abnormal LVEF (< 30%), while the rest of the patients were classified as class I NYHA HF with mildly abnormal LVEF (41-53%).Our study demonstrates that in patients experiencing CTRCD, right ventricular function is lower than baseline as measured using RVFWLS. RV dysfunction was seen in 25% of CTRCD patients by RVFAC, a conventional parameter, analogous to LVEF, and in up to 75% patients based on the strain analysis by STE, using a vendor independent, cardio-oncology specific software. The proportion of patients with abnormal RVFWLS was larger than those with abnormal RVFAC, demonstrating the sensitivity of strain measures to identify subtle RV dysfunction.Currently, RV dysfunction is not considered in the diagnosis of CTRCD and its incidence and prognostic value in patients receiving potential cardiotoxic therapy have not been adequately studied. The limited literature on the impact of cancer therapy on the RV may reflect the absence of robust techniques for the assessment of RV function. However, given the thinner structure of RV with fewer myofibrils, the RV may also be susceptible to damage by the cardiotoxic cancer therapy, as we have shown in this study. In fact, American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) experts’ consensus on proper cardiac care of adult patients receiving cancer treatment recommends RV function monitoring during cancer therapy.12. More recently, 46 women with breast cancer receiving anthracyclines were studied using cardiac magnetic resonance (CMR) and showed RV dysfunction in 34% of the patients after 12 months follow-up, while LV dysfunction was seen in 26%13. In the same study, RV dysfunction was present as early as after 4 months of therapy, and was interpreted as an early sign of myocardial injury. An echocardiography study identified mild reduction in RVFAC and TAPSE in 37 patients with breast cancer treated with anthracyclines14, although mostly in the normal range.The effect of cancer therapy on the RV was first demonstrated in an older study on 41 patients with various cancers and with anthracycline-based treatment by radionuclide ventriculography and based on wall motion abnormalities15,16. Interestingly, in a more recent study of patients with advanced HF receiving LV mechanical circulatory support, patients with CTRCD were significantly more likely to also require RV mechanical support17.Two studies of 19 and 56 survivors of pediatric cancers and treated with anthracyclines have shown a reduction in RVFWLS as a marker of subclinical ventricular dysfunction18. The study showed a lower propensity for subsequent ventricular function recovery although this did not reach statistical significance due to the small sample size.The incidence of concomitant RV dysfunction at the time of CTRCD by RVFWLS has been recently studied in 30 patients with HER2+ breast cancer treated with trastuzumab with or without anthracyclines and concomitant RV dysfunction was seen in up to 40% of the patients19,20. Moreover, RVFWLS sensitively predicts dyspnea development in breast cancer patients receiving epirubicin therapy21.Investigations that have followed breast cancer patients undergoing anthracycline-based chemotherapy for at least one year agree that right ventricular structure, systolic/diastolic function and mechanics are significantly impairedFuture work should be conducted to determine if right heart dysfunction precedes left heart abnormalities, potentially permitting earlier detection and possible intervention strategies to prevent chemotherapy-induced cardiac dysfunction in this particular population.Our work builds on the existing literature demonstrating that in patients experiencing CTRCD, longitudinal strain analysis allows the identification of subclinical RV dysfunction when conventional indices of RV function are unaffected.22, involving 2625 patients (mean follow-up 5.2 years), showed a 9% overall incidence of cardiotoxicity after anthracycline treatment, and 98% of cases occurred within the first year and were asymptomatic. In our study cardiotoxicity incidence was 29%, including symptomatic and asymptomatic LVEF drop along with transitory CTRCD.A recent study by Cardinale et al.23.RVFWLS computed by the average from the three segments of the RV free wall was preferred to other techniques based on our clinical experience that noted this approach as being the most feasible and reproducibleIdeally, LVGLS should be considered alongside LVEF when interpreting longitudinal data for CTRCD monitoring, and moreover, including RV function assessment. Currently, strain measurements are dependent on the analysis software, which is usually limited to proprietary formats generated by a specific imaging system. The major limitation for the use of strain parameters is the inter-vendor variability, resulting in dependency on the analysis software, which is usually limited to proprietary formats generated by a specific imaging system.3 suggests that: early detection of high-risk patients, prompt diagnosis of CTRCD, the use of imaging modalities that provide additional relevant clinical information (e.g. RV function) and consistency regarding the imaging modality assay for continued screening throughout the treatment pathway, should be fundamental tasks for the management of cancer patients, involving both cardiologists and oncologists.The new Position Paper of the European Society of Cardiology (ESC) on cancer treatments and cardiovascular toxicityIn this sense we used a vendor-independent with a dedicated cardio-oncology platform, which uses DICOM images for the analyses of volumes and strain, in an easy-to-understand display and rapid interpretation of serial images.24. It was noted a moderate but statistically significant bias between vendors that was, however, within acceptable limits for most combinations of software packages. Authors concluded that LVGLS may be safely used in routine clinical practice but should preferably be interpreted relative to previous examinations with the same machine and software or versus vendor-specific reference values.In a head-to-head comparison of LVGLS measurements using STE software packages from seven different ultrasound machine vendors and two software-only vendors, the performance of nonvendor-specific software did not differ from that of vendor-specific packagesRVFWLS appears to be reproducible and feasible for clinical use, but because of the need for additional normative data from large studies involving multivendor equipment, no definite reference ranges are currently recommended for either global or regional RV strain or strain rate.This was a retrospective study from a single center with a relatively small sample size. However, the low rates of CTRCD at our center and the lack of universally accepted follow-up explain our small sample size. Furthermore, we used an age and cardiac risk factor balanced control group of Hematology and Oncology patients who had echocardiography prior to any cancer treatment to account for this limitation.After the end of chemotherapy, follow-up data was present only in 35% (n = 7) of the CTRCD patients. This reflects the retrospective nature of the study, and the fact that many patients are not routinely followed with cardiac imaging at our tertiary care center once cancer therapy is completed. Therefore, it is not possible to estimate ventricular function recovery; we consider this as the most important limitation. Further studies are needed to define the clinical and prognostic significance of RVFWLS reduction in cancer patients and whether LV dysfunction recovery would be influenced during follow-up in patients with RVFWLS decrease. Furthermore, concomitant RV dysfunction may have implications for cardiac therapy in patients experiencing cardiotoxicity.In our study patients have a certain variability in the way their malignancy was treated. However, all patients received potential cardiotoxic therapy with a majority (75%) having received anthracyclines. We also did not report chemotherapy dose/kg as it was not the objective of our study.Finally, we did not do a logistic regression because the sample size was too small to obtain meaningful results.The number of studies demonstrating that right ventricular structure, function and mechanics are valuable predictors of cardiovascular and total morbidity and mortality in patients with a wide range of cardiovascular conditions is constantly increasing.The presence of RV dysfunction during cardiotoxicity in our study demonstrates the need to assess both ventricles function during cancer therapy. This is consistent with recent ESC guidelines, which encourages routine follow-up of both LV and RV functions during cancer treatment. Our finding is a hypothesis that needs to be confirmed in larger studies.The appropriate length of cardioprotection or HF treatment in patients experiencing cardiotoxicity during cancer therapy is unknown, but definitely it is influenced by the coexistent RV dysfunction. In addition, these patients may need close cardiology follow-up.RV dysfunction may be a marker of more significant cardiac injury and a potential risk factor for persistent LV dysfunction during follow-up.Combined results and collective evidence generated using different echocardiographic parameters will provide deeper insights into the pathology of this intriguing pathology, ultimately translating into more accurate diagnosis and better clinical management of cardiovascular complications in cancer patients. Incorporating new echocardiographic parameters for LV and RV assessment into clinical cardio-oncology trials may ultimately prove useful in defining the cardiotoxic profile of new and existing chemotherapeutic agents.Longitudinal strain analysis allows the identification of subclinical RV dysfunction in patients with cancer therapy-related LV dysfunction when conventional indices of RV function are unaffected. This demonstrates the need to assess both ventricles function in patients receiving potential cardiotoxic treatment that may have major implications in cancer patients’ management.Better prediction of CTRCD may support the identification of patients who can benefit by closer surveillance during and after exposure to potentially cardiotoxic chemotherapy, decrease the number of cardiac complications and further increase the life expectancy of patients suffering from cancer.Further studies are needed to define the clinical and prognostic significance of RVFWLS reduction in cancer patients.◊ The presence of right ventricle dysfunction demonstrates the need to assess both ventricles function during cancer therapy◊ Right ventricle dysfunction is an early sign of myocardial injury in cancer therapy-related cardiotoxicity, and longitudinal strain analysis allows the identification of subclinical dysfunction when conventional indices of right ventricle function are unaffected◊ Future work should be conducted to better understand the place of the right ventricle in the spectrum of cancer therapeutics-related cardiac dysfunction