The availability of ultra-miniaturized pocket ultrasound devices (PUD) adds diagnostic power to the clinical examination. Information on accuracy of ultrasound with handheld units in immediate differential diagnosis in emergency department (ED) is poor. The aim of this study is to test the usefulness and accuracy of lung ultrasound (LUS) alone or combined with ultrasound of the heart and inferior vena cava (IVC) using a PUD for the differential diagnosis of acute dyspnea (AD).We included 68 patients presenting to the ED of “Maurizio Bufalini” Hospital in Cesena  for AD. All patients underwent integrated ultrasound examination (IUE) of lung-heart-IVC, using PUD. The series was divided into patients with dyspnea of cardiac or non-cardiac origin. We used 2 × 2 contingency tables to analyze sensitivity, specificity, positive predictive value and negative predictive value of the three ultrasonic methods and their various combinations for the diagnosis of cardiogenic dyspnea (CD), comparing with the final diagnosis made by an independent emergency physician.LUS alone exhibited a good sensitivity (92.6%) and specificity (80.5%). The highest accuracy (90%) for the diagnosis of CD was obtained with the combination of LUS and one of the other two methods (heart or IVC).The IUE with PUD is a useful extension of the clinical examination, can be readily available at the bedside or in ambulance, requires few minutes and has a reliable diagnostic discriminant ability in the setting of AD. Acute dyspnea is one of the most frequent symptoms of patients presenting to the emergency department (ED), with about 4–5 million hits per year in the United States . The difFocused cardiac ultrasound plays an important role in the diagnostic evaluation of the patient at bedside and it is important for triage decisions and emergency treatment . Large aIn the setting of ED standard echocardiographic equipment may be heavy and difficult to handle while hand-carried ultrasound devices have been developed for bedside use. In particular, the ultrasound technology pool has been enriched with pocket ultrasound devices that offer advantages in terms of portability and speed, and are able to reproduce images with standard ultrasound and color Doppler. These devices can be used as first ultrasound approach in ED and ambulance and confer added diagnostic power to the clinical examination in populations of patients with no history of cardiovascular disease , 10.Informations on accuracy of first diagnostic assessment with pocket ultrasound device in immediate differential diagnosis for acute dyspnea in ED are still deficient. The aim of this study is to test the utility and accuracy of LUS alone or combined with ultrasound of the heart and IVC in the identification of CD with pocket ultrasound device in ED.From November 2014 to August 2015 we enrolled 68 patients presenting to the ED of “Maurizio Bufalini” hospital in Cesena  for acute dyspnea or sudden worsening of chronic dyspnea within the previous 48 h. All patients underwent clinical exam, blood gas analysis, chest X-Ray, ECG, routine blood tests and integrated ultrasound examination of lung-heart-IVC with pocket size device Vscan  with a single probe (1.7–3.8 MHz), using abdominal preset for lung and cardiac preset for heart and IVC. Ultrasound examination was performed in semi sitting or supine position by one emergency physician expert in transthoracic echocardiography (ASE level III) and with good experience of LUS who was not taking care of the patient  allowing qualitative evaluation of left ventricular systolic function, size of chambers and the presence or absence of pericardial effusion. Ejection fraction (EF) was estimated visually and categorized as preserved if >40% or reduced if ≤40% .The IVC was explored in subcostal view and evaluated by the presence or absence of dilatation (> 2 cm) and hypo-reactivity with breathing (variation of size <50%) .The final diagnosis of acute dyspnea was determined by an independent emergency physician (blind to the integrated ultrasound examination) who has followed each patient, taking into account all the clinical investigations performed  and the evolution of the patients . Without knowledge of the ultrasound data collected in the ED, he had to classify patients into 2 groups: cardiogenic dyspnea (CD) and dyspnea of non-cardiac origin (non-CD). The primary end point was to compare the diagnostic performance of cardiopulmonary ultrasound with pocket size device and standard examinations  for the diagnosis of CD. Specifically, for the diagnosis of CD, the Boston-score diagnostic criteria (points 5–12) have been always satisfied .In patients with coexistence of heart failure and another cause of dyspnea the main diagnosis was considered CD .Another emergency physician expert in lung and cardiac ultrasound read all images, blind to the final diagnosis from the ED.t-test while χ 2 distribution was used to compare categorical variables.Data were analyzed using SPSS version 21.0 . Continuous data are expressed as mean ± 1 standard deviation and categorical variables as percentages. Quantitative variables were compared by using Student’s The population was divided into patients with CD and patients with non-CD. Contingency tables were produced to analyze sensitivity, specificity, positive predictive value and negative predictive value of the three ultrasonic findings obtained with pocket size device and their various combinations for the diagnosis of CD, based on the final diagnosis made by the emergency physician. Receiver operating characteristic (ROC) curves (AUC) are used to describe and compare the performance of each different ultrasound modality  and the combination between bilateral IS/effusion and only 1 of the cardiovascular abnormalities (EF ≤40% OR dilated and not collapsing IVC) versus the final ED diagnosis .p-value <0.05 was considered statistical significant.A Our study population included 68 patients  with a mean age of 78 years. Table p < 0.05) and have tendencies to have higher Lactate and creatinine levels and lower C-reactive protein compared to patients with non-CD . The presence of numerous B-lines, sometimes confluent, configures the framework of an alveolar-interstitial syndrome . It may In our analysis, the presence of bilateral IS and/or effusion exhibits a high sensitivity for the diagnosis of CD, with a high negative predictive value, confirming the pathophysiological assumption that in acute heart failure interstitial edema or effusion are present bilaterally and confirming the diagnostic importance of LUS in patients with decompensated heart failure , 25. AmoThe presence of EF less than or equal to 40% has a low sensitivity for the diagnosis of dyspnea related to acute cardiac decompensation. This reflects the fact that a significant proportion of patients with HF presents with preserved EF . HoweverThe presence of dilated and not collapsing IVC is typically an accurate index of increased right atrial pressure that can be a result of either an increased pulmonary arterial pressure or right ventricular dysfunction with or without significant tricuspid regurgitation . In our The combination of bilateral IS/effusion and EF ≤40% has a better accuracy than the association between bilateral IS/effusion and dilated and not collapsing IVC for the diagnosis of CD. The contemporary presence of all three ultrasound abnormalities has not an optimal accuracy, especially because of the poor sensitivity.In the diagnosis of acute heart failure the combination of reduced left ventricular EF and poor collapsibility of IVC has been demonstrated to have high specificity and sensitivity for the diagnosis of HF , with anConsistently, the association between bilateral IS/effusion and only 1 of the cardiovascular abnormalities (EF ≤40% or dilated and not collapsing IVC) improves the sensitivity and accuracy compared to the association between bilateral IS/effusion and EF ≤ 40%, because it captures also patients with HF with preserved ejection fraction among whom many have dilated and not collapsing IVC.Kajimoto et al. who showed accuracy (93.3%) slightly greater than our study. This difference possibly reflects the fact that in our protocol color Doppler was not available and only EF was the parameter of LV function detectable during cardiac ultrasound, whereas in their protocol cardiac ultrasound was considered diagnostic also with EF >40% when associated with moderate to severe mitral regurgitation [The diagnostic value of lung-cardiac-IVC integrated ultrasound was recently tested by gitation  expandinOur study has some limitations. First, the population sample could be larger. However our findings are consistent with previous reports , 12. It Overall, the integrated lung-heart-IVC ultrasound examination improves the accuracy of LUS alone, by maximizing specificity, and allowing to capture different types of heart failure. This makes pocket ultrasound devices useful for the efficiency and speed in the differential diagnosis of acute dyspnea in the ED.The IUE of lung-heart-inferior vena cava with pocket ultrasound devices is an extension of the clinical examination and can be realized with a protocol that provides 4 thoracic scans , at least one view  which enables the assessment of LV systolic function and the subcostal view for the inferior vena cava. This method is readily available at bedside or even in ambulance, requires few minutes and has reliable diagnostic accuracy in the management of acute dyspnea.


P = 0.004; I2 = 94.5%), and increased the incidence of complete ST-segment resolution . Remote ischemic conditioning patients had a lower risk of all-cause mortality  and lower major adverse cardiovascular and cerebrovascular events rate . Meta-analysis suggested that remote ischemic conditioning conferred cardioprotection by reducing myocardial enzymes and increasing the incidence of complete ST-segment resolution in patients after STEMI. As a result, clinical outcomes were improved in terms of mortality and incidence of major adverse cardiovascular and cerebrovascular events.We conducted a systematic review and meta-analysis to evaluate the effects of remote ischemic conditioning on myocardial parameters and clinical outcomes in ST segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention. Ten eligible randomized controlled trials with 1006 STEMI patients were identified. Compared with controls, remote ischemic conditioning reduced the myocardial enzyme levels (standardized mean difference =-0.86; 95% CI: -1.44 to -0.28;  Timely reperfusion to ischemic myocardium after ST segment elevation acute myocardial infarction (STEMI) can result in obvious myocardial ischemia/reperfusion (I/R) injury, which may impair the clinical benefit of primary percutaneous coronary intervention (PPCI) . ConsideRemote ischemic conditioning (RIC) was first introduced by Przyklenk et al. in 1993 . By applFigure P = 0.004] with significant heterogeneity (I2 = 94.5%) . Sensitivity analysis excluding each included study one at a time revealed that most individual studies were consistent with the direction and size of the overall myocardial enzymatic effect (All P ≤ 0.02)  =-0.86; 95% CI: –1.44 to –0.28; ) Figure . No evid) Figure .P = 0.020; I2 = 47.9%] . Sensitivity analysis excluding each included study one at a time revealed that most individual studies were consistent with the direction and size of the overall cSTR-improving effect (All P ≤ 0.08)  = 1.74; 95% CI: 1.09 to 2.77; ] Figure . No evid) Figure .P = 0.16; I2 = 93.6], the imaging IS , myocardial edema  or LVEF  (Table RIC did not affect the extent of MSI [weighted mean differences (WMD) = 0.09; P = 0.002; I2 = 0.0%), , especially in the subgroup with ≥ 1 year follow up   was reported in 635 study subjects, and the overall incidence was 5.0% . Postoperative incidence of death was significantly reduced by RIC  Figure .P = 0.002; I2 = 0.0%), particularly in the subgroup with ≥ 1 year follow up  . The risk of postoperative MACCE was significantly lowered in the RIC group  Figure .The incidence of recurrent MI, TVR, stent thrombosis, stroke, and HF was 4.72% (22/466), 2.65% (5/189), 1.04% (1/96), 1.85% (10/542), and 3.88% (18/464) respectively. There was no significant difference between the RIC group and the control group for these endpoints as shown in Table In this meta-analysis of ten randomized trials involving 1006 patients, we confirmed that RIC conferred cardioprotection compared to primary PCI alone by reducing elevated myocardial enzyme and increasing the incidence of cSTR in patients after STEMI. No beneficial effect on MSI, myocardial edema, imaging IS, or LVEF was observed. Our study demonstrated that RIC also improved clinical outcomes regarding all-cause mortality and incidence of MACCE.PCI remains one of the two current cornerstones in the treatment of STEMI patients. However, the incidence of heart failure ≈ 25%) and cardiac death (≈ 10%) after PPCI remains high, partly due to myocardial ischemia/reperfusion (I/R) injury . Paradox% and carRIC is another endogenous protective approach by inflation of an upper-arm blood pressure cuff, which is more applicable and less harmful than IPoC in clinical settings . Our comThe baseline TIMI flow grade before reperfusion therapy for STEMI has been recognized as an influential factor of post-PPCI myocardial injury . The myoIn the pooled analysis of the RIC-induced protective effect on myocardial parameters, the value of I-squared for the heterogeneity test ranged from 48.0% to 94.1%. Although the exact sources of significant heterogeneity for ischemic conditioning in this setting remain unknown, previous meta-analysis evidence showed that age , sex , stenting technique  , andβ-blThe robustness of pooled outcomes in our meta-analysis included the evaluation of publication bias and sensitivity analysis. However, the number of included trials or patients in the analysis may be not adequate to draw a definite conclusion. In our analysis, no evident publication bias was observed in myocardial enzyme level and the incidence of cSTR. Sensitivity analysis confirmed that the contributions of each trial to the overall pooled estimates of myocardial enzyme level and the incidence of cSTR were similar. Future meta-analyses should verify these findings.ATP channels [Although RIC could elicit cardioprotection in patients with STEMI, the underlying mechanisms are not entirely understood. Various animal and human studies have shown that RIC in the peripheral organs could induce the humoral and neuronal transfer of the protective factors to the remote heart , 40. Thechannels , aldehydchannels , and mitchannels . Slagsvochannels  and leftchannels  of patieThe strengths of this meta-analysis included a comprehensive analysis of clinical outcomes (MACCE), robust approach  , 54, sufAvailable evidence from the present meta-analysis suggested that RIC may confer cardioprotection by reducing elevated myocardial enzymes and increasing cSTR incidence in patients after STEMI. Furthermore, our study showed that RIC improved clinical outcomes regarding all-cause mortality and incidence of MACCE.PubMed, EMBase, and Cochrane Library (up to June 2017) using keyword terms “ischemic conditioning,” “remote ischemic conditioning,” “acute myocardial infarction,” and “percutaneous coronary intervention.” Prospective RCTs enrolling STEMI patients undergoing PPCI were included. The exclusion criteria were: 1) non-English published trials, 2) STEMI patients undergoing thrombolysis, 3) unreported myocardial parameters or clinical outcomes, and 4) RIC combined with other interventions.A systematic search was performed according to the PRISMA statement  in PubMeThe literature review and data extraction were independently completed by two investigators (X.S. and W.P.). Discussion was conducted to reach consensus in case of any disagreements. Quality assessment was conducted using Jadad scoring system  of randoData extraction of study characteristics included trial design , and patient demographic data .The postprocedural myocardial parameters of interest were as follows: myocardial enzyme levels, the incidence of cSTR, MSI, imaging IS, myocardial edema, and LVEF. The area under the curve (AUC) of total serum troponin or creatine kinase isoenzyme MB (CK-MB) level was preferable in the analysis for its potential superiority. If AUC data were not available, peak troponin or CK-MB or CK level was extracted in turn.The clinical outcomes with ≥ 1 month follow-up were included as follows: all-cause mortality, the incidence of recurrent MI, TVR, stent thrombosis, stroke, and HF. The MACCE were also extracted as a composite endpoint of the included clinical outcomes.P < 0.05 (2-sided) was considered statistically significant. All statistical analysis was performed with Stata software .For continuous results (reported with mean and standard deviation or median and interquartile range), we calculated standardized mean differences (SMD) of myocardial enzymes and weighted mean differences (WMD) of LVEF, IS, MSI, and myocardial edema to obtain the pooled estimates with 95% confidence intervals (CI). For dichotomous outcomes (reported with incidence), we calculated the odds ratio (OR) with 95% CI. The random-effect model was used for analysis in consideration of potential clinical inconsistency. Publication bias was assessed by Begg’s and Egger’s test. Sensitivity analysis was used to identify the influence of each included study on the overall estimate of myocardial enzyme and incidence of cSTR. A


Early synthetic gadolinium enhancement (ESGE) imaging from post-contrast T1 mapping after adenosine stress-perfusion cardiac magnetic resonance (CMR) was compared to conventional late gadolinium enhancement (LGE) imaging for assessing myocardial scar.Two hundred fourteen consecutive patients suspected of myocardial ischaemia were referred for stress-perfusion CMR. Myocardial infarct volume was quantified on a per-subsegment basis in both synthetic (2–3 min post-gadolinium) and conventional (9 min post-gadolinium) images by two independent observers. Sensitivity, specificity, PPV and NPV were calculated on a per-patient and per-subsegment basis.p=0.39). Excellent correlation (r=0.997) and agreement (mean absolute difference: -0.028±0.289 ml) were found between ESGE and LGE images. Sensitivity, specificity, PPV and NPV of ESGE imaging were 96 (78.9–99.9), 99 (97.1–100.0)%, 96 (76.5–99.4) and 99.5 (96.6–99.9) in patient-based and 99 (94.5–100.0), 100 (99.9–100.0)%, 97.0 (91.3–99.0) and 100.0 (99.8–100.0) in subsegment-based analysis.Both techniques detected 39 gadolinium enhancement areas in 23 patients. The median amount of scar was 2.0 (1.0–3.1) g in ESGE imaging and 2.2 (1.1–3.1) g in LGE imaging (ESGE based on post-contrast T1 mapping after adenosine stress-perfusion CMR imaging shows excellent agreement with conventional LGE imaging for assessing myocardial scar, and can substantially shorten clinical acquisition time.Synthetic gadolinium enhancement images can be used for detection of myocardial scar.• Early synthetic gadolinium enhancement images can substantially shorten clinical acquisition time.• ESGE has high diagnostic accuracy as compared to conventional late gadolinium enhancement.• Quantification of myocardial scar with ESGE closely correlates with conventional LGE.• ESGE after stress perfusion CMR avoids need for additional gadolinium administration.•  The clinical evaluation of chronic myocardial infarction includes the evaluation of late gadolinium enhancement (LGE) in the myocardium using contrast-enhanced cardiovascular magnetic resonance (CMR) imaging . CurrentIn a recent study, synthetic IR LGE images were compared to conventional IR LGE imaging in patients with suspected myocardial infarction, both obtained after a regular waiting time after gadolinium injection of 10–15 min. This study showed a high sensitivity (90 %) and specificity (96 %) of the synthetic IR images for the detection of LGE as compared to conventional IR LGE images . FurtherWe hypothesised that the timing of acquisition after intravenous gadolinium to detect myocardial scar can be significantly reduced using synthetic IR imaging. We studied whether we can advance to early synthetic gadolinium enhancement (ESGE) imaging by obtaining TI data 2 min after the first-pass perfusion imaging under adenosine stress, without an additional dose of gadolinium, with similar sensitivity and specificity to conventional LGE imaging for the assessment of myocardial scar.The institutional review board approved this prospective study. All patients provided written informed consent before enrolment in the study. Between August 2015 and January 2016, 214 consecutive patients suspected of myocardial ischaemia were enrolled for adenosine stress CMR, after excluding common contraindications for MR imaging, gadolinium and adenosine. Conventional LGE was considered the standard of reference in this study for the detection and quantification of myocardial scar.A 1.5 T system  with phased-array radiofrequency coils was used in all patients. Adenosine stress-only perfusion MRI was performed according to conventional methods. A standard 40-s perfusion sequence was started during the first pass of 0.1 mmol/kg gadopentetate dimeglumine, injected at a flow rate of 5 ml/s, after 3 min of adenosine infusion. The research sequence, namely post-gadolinium T1 mapping, was performed exactly 2 min after the start of the bolus injection of gadolinium for the perfusion series. For the current study, equal position and orientation of 5 short-axis slices were used in post-gadolinium T1 mapping and the conventional LGE imaging. An additional dose of contrast material (0.05 mmol/kg) was given directly after the last T1-mapping sequence, followed by conventional LGE images 9 min after the second dose of gadolinium. Synthetic IR images were calculated automatically from the post-gadolinium T1 map.2; echo time 1.09 ms; bandwidth, 1,085 Hz/ pixel; flip angle, 35°; and parallel imaging acceleration factor, 2.After the standard adenosine stress perfusion series, an investigational modified Look-Locker inversion recovery (MOLLI)-based post-gadolinium T1-mapping sequence (WIP780B) was used to acquire a pixel-wise T1 map of the myocardium. In each patient five short-axis T1 maps were acquired equally divided over the left ventricle with a distance factor of 8 mm, during a short breath-hold (10–11 s) at end-expiration. A 4(1)3(1)2 sampling scheme of the heart was performed, including nine images in 11 heartbeats. An adiabatic inversion pulse was used to improve inversion efficiency. For the MOLLI acquisition, an initial TI of 100 ms was used with 80 ms TI increment. The images were generated using a single-shot steady-state free-precession readout. T1 maps were generated on the imaging unit by using a three-parameter signal model. The calculated T1 for each pixel (T1 map) was used to create series of quantitative synthetic IR images in short-axis view with inline respiratory motion correction. Each synthetic image series consisted of 40 images with TI increments of 25 ms, starting at 200 ms. Typical parameters were: slice thickness, 8 mm; reconstruction matrix 256 × 192; in-plane spatial resolution, 1.65 × 1.65 mm2; TI 300 ms; echo time 1.09 ms; bandwidth, 1,085 Hz/pixel; flip angle, 65°; and parallel imaging acceleration factor, 2.Conventional LGE imaging involved a cardiac-gated single-shot gradient-echo pulse sequence with full coverage of the left ventricle, during two breath-holds at end-expiration. The sequence included nine continuous short-axis slices, in which the short-axis section position and orientation were copied from the T1-mapping acquisition. Typical parameters were: slice thickness, 8 mm; reconstruction matrix 192 × 170; in-plane spatial resolution, 1.77 × 1.77 mmESGE and conventional LGE images were analysed by two blinded observers for agreement regarding localisation and extent of the myocardial scar. The MR protocol is shown in Fig. The images were analysed using commercially available software . Endo- and epicardial contours of the left ventricle were drawn manually. A reference point was placed outside and below the inferior wall of the left ventricle in short-axis direction. The software automatically divided the myocardium into six  or four  segments according to the American Heart Association’s segment model .In each patient two sets  of five equal-positioned short-axis slices were evaluated. At both basal and mid-ventricular level two short-axis slices each were taken, and one slice at apical level, which gave a total of 28 subsegments per left ventricle.A binary threshold algorithm that uses five standard deviations above the average signal intensity of the normal myocardium was applied to automatically delineate the area showing gadolinium enhancement . Pixels U test (unpaired data) or Wilcoxon signed rank test (paired). Differences in gadolinium enhancement areas were analysed with the paired t test. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated on patient- and subsegment-based analysis. The correlation between ESGE and conventional LGE was evaluated with linear regression analysis using Pearson’s correlation coefficient. Interobserver variability was assessed by calculating the interclass correlation coefficient for both ESGE and LGE. To assess the agreement and potential systematic differences between the readers and imaging techniques Bland-Altman analysis was performed indicating mean difference and 95 % limits of agreement. Statistical significance was defined as a p-value of <0.05. Statistical analyses were performed by using SPSS statistics 23 .Continuous variables without normal distribution were reported as median with interquartile range and compared by the Mann-Whitney 2. The maximal heart rate during adenosine infusion was significantly higher compared to the resting heart rate (p<.0001).Twenty-three (10.7 %) patients had 39 gadolinium enhancement areas consistent with myocardial scars. The mean age of the study population with myocardial scar was 68±11 years, 17 (81 %) patients were male, 4 (19 %) patients had diabetes, and the mean body mass index (BMI) was 28±5 kg/mThe patterns of enhancement were consistent with myocardial scar in each patient. The ESGE and conventional LGE technique detected areas of enhancement in 21 corresponding patients. The ESGE images were false-negative in one patient (one subsegment) and false-positive in one patient (three subsegments).In the 23 patients with gadolinium enhancement 644 subsegments were evaluated. Gadolinium enhancement consistent with myocardial scar were detected in 101 of 644 subsegments in 23 patients, whereas 5,348 subsegments in 191 patients (191 × 28) were considered normal. The total number of true-negative subsegments was 5,891 . When comparing ESGE to conventional LGE as standard of reference for detection of myocardial scar, sensitivity, specificity, PPV and NPV were 96 % (78.9–99.9), 99 % (97.1–100.0), 95.8 (76.5–99.4) and 99.5 (96.6–99.9), respectively, for patient-level analysis and 99 % (94.5–100.0), 100 % (99.9–100.0), 97.0 (91.3–99.0), and 100.0 (99.8–100.0), respectively, for segment-based analysis.. Quantitative analysis of myocardial scar was performed in 21 patients and 97 subsegments. The median amount of gadolinium enhancement was 2.0 (1.0–3.1) g in the early synthetic images and 2.2 (1.1–3.1) g in the conventional images (p=0.386). A representative example of gadolinium-enhancement detection by ESGE and conventional LGE is shown in Fig. The two patients with false-negative and false-positive findings were excluded from further quantitative analysis 2.0 1.0–.1 g in tp-value <.001 for both ESGE and conventional LGE with a mean difference of -0,0585±0,0826 g and -0.0596±0.09117 g , respectively. Interobserver correlation and agreement are shown in Fig. The ICC was 0.999 (0.998–1.000) at a We demonstrated that early enhancement of myocardial scar with post-contrast T1 mapping performed directly after adenosine perfusion CMR showed excellent correlation and agreement with conventional IR LGE. Our results show high sensitivity and specificity between ESGE and conventional LGE images as assessed by semi-automated evaluation. The ESGE images can be generated directly after the stress-perfusion CMR images for the detection of myocardial scar to differentiate ischaemic perfusion defects from non-ischaemic perfusion defects.The normal delay time after the stress perfusion acquisition is about 10 min, which is a considerable part of the scan time. In this study we showed that ESGE imaging generated from post-gadolinium T1 mapping may eliminate the need for conventional LGE imaging, which reduces scan time and avoids additional administration of gadolinium. The early detection of gadolinium enhancement on the T1-mapping-based images 2 min after contrast injection as compared to the conventional LGE images can be explained by several factors.First of all, the mechanism of early enhancement relates to the different wash-in and wash-out kinetics of normal myocardium and myocardial scar. The extracellular volume fraction in areas of myocardial scar is higher than that in regions with normal myocardial tissue. The hyperaemia induced by adenosine, facilitates wash-in of gadolinium in the extracellular volume, especially in the regions of infarcted myocardium. These regions will have a higher concentration of gadolinium and subsequently greater T1 shortening . SecondlThe results in our study showed that quantification of ESGE imaging in patients with myocardial scars was feasible and reproducible. The amount of scar based on ESGE imaging was comparable to conventional single-shot PSIR LGE imaging, which was used as the standard of reference. ESGE imaging resulted in one false-negative finding. In one patient a subendocardial enhancement area (one subsegment) was not detected, probably due to the fact that this scan was performed too early after administration of gadolinium. Conventional single-shot PSIR LGE failed to view one subendocardial scar (three subsegments) in the lateral wall mainly due to the relative high density of the blood-pool contrast.In this study we used a standard semi-automated analysis to quantify the infarct areas with commercially available software. We set a threshold of five standard deviations above the average signal intensity of the normal myocardial tissue. This threshold has been proven to be most accurate among the binary techniques in quantification of myocardial infarction .Compared to the reference LGE images, ESGE images improve infarct border visualisation without oversaturation of the region of interest, especially concerning the blood pool area. The demarcation of endocardial contours in the infarcted areas in this study was more simple to perform in the ESGE images compared to the LGE images. In this study, despite the manual input to draw the inner and outer lines of the left ventricle, the interobserver correlation coefficients between synthetic and conventional images were excellent. This new quantitative T1-mapping-based enhancement technique, if used as full coverage of the left ventricle, has the potential to be used in the evaluation of myocardial viability and scar volume assessment (Table In this study we used single-shot PSIR as standard of reference for LGE. It is known that segmented 2D and 3D sequences for LGE, compared to single-shot PSIR, has a better in-plane resolution and a better definition of the infarcted area; however, in this study we used single-shot PSIR mainly because the in-plane resolution is comparable to the ESGE images.We avoided full coverage of the left ventricle in this study protocol because we aimed to preserve a fixed short time-interval between the different gadolinium enhancement techniques. Too many T1 maps may represent different states of contrast enhancement, which could interfere with the results. The quantification of the total volume of infarct in this study was not possible because only five short-axis slices were used for analysis.In our study a breath-hold of 10–11 s was sufficient for acquiring the synthetic PSIR images. We recognise, however, that the acquisition time of synthetic PSIR is longer compared to single-shot PSIR conventional LGE imaging. In patients with chronic obstructive pulmonary disease, heart failure or elderly patients the breath-hold instructions may be a problem.The heart-rate increasing effects of adenosine can influence the quality of the MOLLI images. However, as shown in our results, there was a strong correlation between the ESGE and conventional LGE images without any decrease in image quality.Because our study population consisted of patients at risk of CAD but without previous documented myocardial infarction, the detected mass of infarcted myocardium was relatively small. We showed that the correlation and agreement between ESGE and conventional LGE was excellent across the whole range of mass of infarcted myocardium. We do not expect different results in a study population with larger areas of infarcted myocardium. However, this new enhancement technique needs further validation before it can be used for full coverage of the left ventricle.The use of early quantitative synthetic IR images from post-contrast T1 mapping after adenosine perfusion CMR can substantially shorten the clinical scan time and avoid the need for an additional bolus of gadolinium. The detection of myocardial infarction as well as reproducibility and agreement of scar volume quantification in ESGE as compared to conventional single shot PSIR LGE images is excellent. Furthermore, infarct border visualisation appears to improve in ESGE images without oversaturation of the ROI.


The role of echocardiography in the risk stratification of acute heart failure (HF) is unknown. Some small studies and retrospective analyses have found little change in echocardiographic variables during admission for acute HF and some echocardiographic parameters were not found to be associated with outcomes. It is unknown which echocardiographic variables will predict outcomes in sub-Saharan African patients admitted with acute HF. Using echocardiograms, this study aimed to determine the predictors of death and re-admissions within 60 days and deaths up to 180 days in patients with acute heart failure.Out of the 1 006 patients in the THESUS-HF registry, 954 had had an echocardiogram performed within a few weeks of admission. Echocardiographic measurements were performed according to the American Society of Echocardiography guidelines. We examined the associations between each echocardiographic predictor and outcome using regression models.Heart rate and left atrial size predicted death within 60 days or re-admission. Heart rate, left ventricular posterior wall thickness in diastole (PWTd), and presence of aortic stenosis were associated with the risk of death within 180 days. PTWd added to clinical variables in predicting 180-day mortality rates.Echocardiographic variables, especially those of left ventricular size and function, were not found to have additional predictive value in patients admitted for acute HF. Left atrial size, aortic stenosis, heart rate and measures of hypertrophy (LV PWTd) had some predictive value, suggesting the importance of early treatment of hypertension and severe valvular heart disease. Recent data clearly indicate that heart failure (HF) is an important healthcare problem in Africa, where it is estimated to constitute about 3–7% of all medical admissions.4Patients with HF are heterogeneous in terms of risk of cardiac death and re-admission for decompensated HF. Therefore assessment of prognosis is a fundamental step in individual patient management. Analysis of clinical variables has helped in identifying the most significant predictors of mortality in the HF population.5Echocardiography has become the gold standard for the evaluation of patients with HF because it is an inexpensive, highly reproducible, widely available and relatively extensive method for assessing left ventricular systolic and diastolic function.7More than 20 echocardiographic parameters have been proposed as predictors of outcome in HF patients in a number of clinical studies.11THESUS-HFTHESUS-HF was a prospective, multicentre, international observational survey of acute HF in 12 cardiology centres from nine countries in sub-Saharan Africa.Patients who were older than 12 years, were admitted with dyspnoea as the main complaint, and were diagnosed with acute HF based on symptoms and signs that were confirmed by echocardiography (de novo or decompensation of previously diagnosed HF) were enrolled consecutively. Patients excluded were those with acute coronary syndromes, severe known renal failure , nephrotic syndrome, hepatic failure or other cause of hypoalbuminaemia.Written informed consent was obtained from each subject who was enrolled into the study. Ethical approval was obtained from the ethics review boards of the participating institutions, and the study conformed to the principles outlined in the Declaration of Helsinki.Details of data collection have been previously described.Electrocardiograms were done and read using standard reference ranges. A detailed echocardiographic assessment was performed (see below). The probable primary cause of HF was provided by the investigators, and was based on the European Society of Cardiology guidelines,Echocardiographic procedures and measurements were performed according to the American Society of Echocardiography (ASE) guidelines.141.04 [(LVIDd + PWTd + IVSTd)3 – (LVIDd)3] – 13.6 g.where LVIDd is left ventricular internal diameter at end-diastole, PWTd is posterior wall thickness in diastole, and IVSTd is interventricular septal thickness in diastole.For diastolic function, left atrial (LA) size (both anteroposterior diameter and planimetry) and pulse-wave mitral-valve (MV) inflow  were measured.Echocardiography examinations also included assessment of valvular architecture, a semi-quantitative estimate of the severity of valvular regurgitation, and determination of the presence of pericardial effusion. Other abnormalities, such as evidence of pulmonary arterial hypertension, were also noted.Patients whose echocardiograph was performed within four weeks prior to and two weeks post enrollment were included in this analysis. Continuous parameters are summarised as means and standard deviation, and categorical parameters by absolute and relative frequencies.For patients who had their E/A ratios recorded, grade 1 was defined as E/A < 0.8, grade 2 as E/A between 0.8 and 1.5, and grade 3 as E/A ratio > 1.5. If a patient had a missing E/A ratio, then the grade was defined using the E-wave deceleration time as follows: grade 1 as E-wave > 200 ms, grade 2 as E-wave 160–200 ms, and grade 3 as E-wave < 160 ms.The associations between echo parameters and clinical outcomes were examined using Cox regression models. The univariate associations between each predictor and outcome were examined. The linearity of associations between continuously distributed predictors and each outcome was assessed using restricted cubic splines with four knots with a test of the significance of the non-linear terms. If the association was non-linear, a readily interpretable transformation was chosen through examination of plots of the predicted log hazard ratio against the value of the predictor and changes in Akaike’s information criterion.For the outcome of 180-day mortality, the associations with creatinine, heart rate and posterior wall thickness were all significantly non-linear. We chose to model creatinine as a quadratic polynomial, and heart rate and posterior wall thickness using linear splines with one knot where the association between predictor and outcome appeared to change.Univariate associations between echo parameters and outcomes are presented for the whole analysis population as well as by key diagnosis groups. Diagnoses were grouped as hypertension, cardiomyopathy, valvular and other. Valvular was defined as having rheumatic heart disease or at least one of the following classified as severe: aortic stenosis or regurgitation, mitral stenosis or regurgitation. To assess whether an association between an echo parameter and outcomes differed by diagnosis group, we tested for the significance of the diagnosis-by-echo parameter interaction term in the Cox regression model for the outcome.The number of events in the analysis population limited development of multivariate models for 180- and 60-day mortality or re-admission. Because of this, we chose a few echo parameters in addition to predictors known to be associated with each outcome in this study population.Multiple imputations were used with a method that assumes multivariate normality (SAS PROC MI) to handle missing values. The imputation model included all covariates under consideration for the multivariate models. The ranges of imputed values were restricted to the ranges of the observed values. Seven imputation datasets were used. Parameter estimates were averaged across these datasets using Rubin’s algorithm (SAS PROC MIANALYZE). Backwards selection was used in each of the seven imputation datasets, with the criterion for staying at p < 0.10. Predictors that were significant in the majority of the imputed datasets were kept in the final model. SAS release 9.2  was used for analyses.There was a total of 1 006 patients in the THESUS-HF registry,Heart failure was most commonly due to hypertension , followed by rheumatic valvular heart disease , and idiopathic dilated cardiomyopathy . Ischaemic heart failure was present in only 71 (7.6%) patients .The distribution and proportion of missing values for each echocardiographic parameter are presented in Univariate associations between the echo predictors and the outcomes by diagnosis groups  suggest that none of the associations of echo parameters with outcomes differed significantly among the diagnostic groups , 3. UnivThe multivariate models suggest left ventricular end-systolic diameter, interventricular septal thickness in diastole, posterior wall thickness in diastole, left atrial size and E/A wave ratio did not add significantly to prediction of 60-day death or re-admission, while left ventricular posterior wall thickness added to clinical variables in the prediction of 180-day mortality , 3.A thorough and complete echocardiographic examination has been shown to be a useful diagnostic test in the evaluation of patients with HF.16In the case of acute HF, the precise association of LVEF with cardiovascular outcomes in patients with acute decompensated HF is controversial.18Various therapeutic interventions can reduce the risk of re-admissions and death in patients admitted with HF. Therefore, identification of patients at the highest risk of re-admission or death could help provide targeted costeffective interventions. Although several studies have assessed potential echocardiographic predictors, the results have been inconsistent.In our study, echocardiographic parameters showed only limited associations between echocardiographic measures and outcomes. Heart rate  and left atrial size were associated with death or re-admission within 60 days, and left ventricular posterior wall thickness and presence of aortic stenosis were associated with the risk of death up to 180 days. In agreement with the results of the PROTECT study modelling,This finding contrasts with data from the ESCAPE study, where echocardiographic measures of LV size and function did change from baseline to follow up and were associated with some outcomes.The results of the current study confirming the preliminary findings of Gandhi et al.Left ventricular hypertrophy (LVH) is a recognised complication of systemic hypertension and the best-studied marker of hypertensive heart disease.The increased risk of patients with severe valvular heart disease, particularly aortic stenosis, is well documented.1c in diabetes mellitus. Furthermore, the left atrium modulates left ventricular filling and cardiovascular performance by functioning as a reservoir for pulmonary venous return during ventricular systole, a conduit for pulmonary venous return during early ventricular diastole, and a booster pump that augments ventricular filling during late ventricular diastole. Therefore, left atrial enlargement (and possibly associated dysfunction) may play an important role not only in the marking of cardiovascular dysfunction but also in its enhancement.Left atrial enlargement has been increasingly suggested in recent years to be an important indicator of increased risk for an adverse clinical outcome. Left atrial enlargement may serve as an indicator for persistent increased pressure within the cardiovascular system, possibly representing longerterm changes, such as the role of HbAThe finding that left atrial size is associated with adverse outcomes begs the question of why measures of diastolic dysfunction were not predictive of such adverse outcomes in the current cohort. Although the reasons for that cannot be ascertained, given the limitations of the study (see below), it is possible that, as described by Gandhi et al.,Increased resting heart rate is a known predictor for cardiovascular mortality and morbidity in a variety of cardiovascular diseases, including HF.26Higher heart rate might also be a marker of greater neurohormonal activation. The SHIFT study showed that heart rate is important in the pathophysiology of HF with reduced LVEF, and that heart rate reduction per se is a mechanism responsible for improvement in clinical outcomes.28The CHARM investigators also found that the value of resting heart rate in predicting worse outcomes was independent of baseline left ventricular systolic function in heart failure.30Similar to our findings, left atrial size or its surrogates have been shown to predict hospitalisation for HF and death in other studies.32Left atrial size, aortic stenosis, heart rate and measures of hypertrophy had some value in predicting outcome in our cohort. This may suggest that early diagnosis and treatment of hypertension and valvular heart disease in sub-Saharan Africa should be emphasised to improve outcome.Our data should be interpreted in the context of their limitations. Unobserved variables may have confounded the results. Not all echocardiographic parameters were available in all patients, limiting the number of parameters for analysis. The variable timing of the echocardiogram and inter-observer variability may have affected the specific results obtained. Furthermore, the number of events was small. Therefore both the variable selection and the parameter estimates for the selected variables are subject to instability.We also looked at echo predictors of acute HF from various causes. Even though there was no statistically significant interaction between the echo variables, different conditions and outcomes, there could still be a dilutional effect of grouping heterogeneous conditions together.Finally, our results are drawn from a population of young acute HF patients predominantly with systolic dysfunction. Consequently, these findings may not apply to older patients or to those with preserved LVEF.In accordance with previous studies, echocardiographic variables, especially those of left ventricular size and function, were found to have little or no additional predictive value in patients admitted for acute HF. Left atrial size was associated with death or re-admission within 60 days while left ventricular posterior wall thickness and the presence of aortic stenosis were associated with the risk of death within 180 days. There is a need for further studies of echocardiographic evaluation, especially when performed closer to the acute event, to further elucidate the pathophysiology and risk stratification of patients with acute HF.


Salt intake is highly associated with cardiac structure in patients with primary aldosteronism (PA). We investigated the association among dietary salt intake, aldosterone and left ventricular mass in patients with PA. We enrolled 158 patients with PA and 158 patients with essential hypertension. We measured 24-hour urinary sodium (UNa) and aldosterone (UAldo) level and echocardiography parameters. In patients with PA, the UAldo level was positively correlated with left ventricular mass index . The UNa level was not linearly correlated with left ventricular structural parameters in patients with PA. To test if UNa has a non-linear relationship with LVMI among patients with PA, we categorized the participants according to the tertile of UNa . PA patients with medium tertile of UNa had significant lower LVMI than the other two groups . Multifactor analysis of variance confirmed this finding after adjustment for clinical parameters. Post-hoc analyses revealed that the high UNa tertile was associated with higher left ventricular end-diastolic volume compared with medium UNa tertile; while the low UNa tertile was associated with higher mean wall thickness compared with medium UNa tertile. The findings imply the reasons for increased LVMI may be different in patients with the highest and lowest UNa tertile. In conclusion, the medium tertile of 24-hour UNa is associated with lowest LVMI in patients with PA. Primary aldosteronism (PA), characterized by excessive production of aldosterone, is now considered to be one of the main causes of secondary hypertension . The repLVH, or increased LV mass, is more common in patients with PA than in those with essential hypertension (EH) or other types of secondary hypertension . LVH devIn patients with EH, dietary sodium intake and plasma aldosterone concentration have been reported to be independently associated with LV mass , 13. In We hypothesized that in patients with PA, the relationship between salt intake and LV mass would be weakest in those with a medium sodium intake, and that the relationship between aldosterone and LV mass would be positive and linear. We conducted this cross-sectional study to evaluate the relationships between 24-hour urinary aldosterone and sodium excretion and LV structural parameters using echocardiography.This cross-sectional study enrolled 158 patients diagnosed with PA from October 2006 to March 2010, all of whom were registered in the Taiwan Primary Aldosteronism Investigation (TAIPAI) database. This database was constructed for quality assurance in one medical center , and its three affiliated hospitals around Taiwan  . AnotherA 24-hour urine sample with the first urine of the day included was collected from all subjects and refrigerated until analysis. The 24-hour urinary sodium and aldosterone amount  were calculated by multiplying the urine sodium or aldosterone concentration by the daily urine amount. When interpreting the results of 24-hour urine collection, we assessed the adequacy of collection by quantifying the 24-hour urine creatinine excretion value, defined as a value between 15 and 20 mg/kg of body weight. The urine samples were stored in plastic containers at 4°C.in vitro using a commercially available radioimmunoassay kit . All antihypertensive medications were discontinued for at least 21 days before measuring plasma PRA and PAC. Diltiazem and/or doxazosin was administered to control markedly high blood pressure when required.The plasma aldosterone concentration (PAC) was measured using radioimmunoassays with commercial kits  . Plasma Fulfillment of the following three conditions was taken to confirm a diagnosis of aldosteronism: (1) autonomous excess aldosterone production evidenced with an aldosterone to renin ratio (ARR) > 35; (2) a TAIPAI score > 60% ; (3) posAldosterone-producing adenoma was identified on the basis of the following four conditions: (1) autonomous excess aldosterone production evidenced with an ARR > 35, a TAIPAI score > 60% , and posIdiopathic hyperaldosteronism was defined on the basis of the following four criteria: (1) autonomous ex-cess aldosterone production evidenced with an ARR > 35, a TAIPAI score > 60% , and posAll echocardiography was performed using a Hewlett-Packard 5500 ultrasound system with an S3 transducer (1.0-3.0 MHz). Transthoracic echocardiographic images were obtained in fundamental imaging modes. Two-dimensional, M-mode, Doppler and tissue Doppler ultrasonography were performed in each patient, and the dimensions of the chamber, wall thickness and left ventricular ejection fraction (M-mode) were measured according to the guidelines of the American Society of Echocardiography .3 - (LV end-diastolic diameter)3]-13.6] [2.7+ 0.64 x stroke work-18.07 x gender  [2 in men and 110 g/m2 in women [LVMI was derived from echocardiography according to the formula reported by Devereux and Reichek: [ LV mass = 1.04 x [3]-13.6] . Predictemale=2) . Left vein women .All continuous variables were expressed as mean ± standard deviation if normally distributed. Non-normally distributed variables were expressed as median and interquartile range. Comparison of continuous variables between the two groups were preformed using the Student's t-test  or Wilcoxon rank sum test . Differences between proportions were assessed using the chi-square test. Urinary aldosterone concentration was log-transformed before the correlation study due to non-normality, which was determined by the Kolmogorov-Smirnov test.Pearson's correlation tests were first used to analyze the correlations between LVMI and 24-hour UAldo or UNa level. Partial correlations were then used to adjust for age, gender and systolic blood pressure. To test the non-linear relationship between urinary aldosterone or sodium and LVMI, we categorized the patients into tertiles according to the UAldo or UNa level . Multifactor ANOVA was performed to test the effect of UAldo or UNa tertile on LVMI, with adjustments for age, sex, mean blood pressure and duration of hypertension. An interaction term of UAldo and UNa was included to test the interaction. According to the LVMI formula, LVMI was determined by both LV wall thickness and end-diastolic volume. Therefore, if the association between UAldo or UNa and LVMI was significant, we further analyzed the association between UAldo or UNa and wall thickness and end-diastolic volume.ANOVA was used separately for the patients with PA and those with EH. Tukey's honest significant difference test was used for post-hoc analysis. All statistical analyses were performed using Stata/SE software version 11.2 for Windows  and R 2.14.0 software .One hundred and fifty-eight PA patients and 158 EH patients were enrolled in this study. The mean age of all participants was 51.8 ± 12.4 years, and the baseline clinical characteristics are shown in Table The correlations between 24-hour UAldo level and PAC were moderate in the patients overall, and in the PA and EH groups . There was no significant correlation between 24-hour UNa level and PAC in the patients overall or in the PA and EH groups.In the patients with PA, the correlations between 24-hour UAldo level and LV mass were significant  . The LVMI values of the patients with low, medium, and high UAldo tertiles were 122.1 ± 31.2, 129.1 ± 34.4, and 146.8 ± 40.2 g/m2, respectively, for the PA group (p=0.003) . These results indicated that among patients with PA, the medium UNa tertile group had a lower LVMI compared to the high and low tertile groups. The clinical characters of PA patients with low, medium, and high UNa tertiles were shown in To test if there were non-linear relationships between UNa or UAldo and LVMI, we plotted LVMI according to UNa or UAldo tertile  and LV end-diastolic volume (LVEDV), we tested the relationship between these two LV structural parameters and 24-hour UNa or UAldo tertile among the patients with PA. The results showed that MWT and LVEDV were significantly different among the three UNa tertiles after adjusting for age, sex, hypertension duration, blood pressure and tertile of UAldo . Post-hoOur results demonstrated that in patients with PA, the 24-hour UAldo level was positively associated with LVMI, while the medium UNa tertile was associated with a lower LVMI compared to the low or high UNa tertiles. These differences in LVMI can partly be explained by the LVEDV in the medium versus high UNa tertiles and by the MWT in the low versus medium UNa tertiles.2) and higher tertile (LV mass index 55.9 ±14.3 g/m2). There is only minimal difference of LV mass between patients with medium and lower tertile (LV mass index 46.4 ±7.3 g/m2). Our results expand the current knowledge about the relationship between the sodium level in PA patients and a wider range of sodium intake and LV structure.The relationships between dietary sodium intake, aldosterone and LV dimension have been previously investigated. Pimenta et al recruited 21 patients with PA and 21 patients with EH matched by age, gender and blood pressure, and found that urinary sodium was positively correlated with LV mass in the patients with PA . The difThe finding that a medium tertile of sodium intake was associated with a lower LV mass has not been reported before in patients with PA and EH. However, U- or J-shaped relationships between sodium intake and hypertension or cardiovascular events have been reported. In a prior study in Taiwan, 24-hour urinary sodium level was curvilinearly associated with incident hypertension among 1520 middle-aged and elderly participants during 7.9 year of follow-up . The parOur study revealed that the increased LVMI in high UNa tertile was associated with increased LVEDV and increased LVMI in low UNa tertile was associated with increased MWT in PA patients. The detail mechanisms whether salt/aldosterone combination promotes cardiac dimension and structure change are still unclear. Both aldosterone and high salt intake induce fluid retention and expand intravascular volume . In the The relationship between sodium intake and LVMI may also be modified by genetic factors. In a previous clinical study evaluating the relationship between angiotensin-converting enzyme (ACE) genotypes and LVMI, a medium sodium intake was associated with a lower LVMI compared to a higher or lower sodium intake in Italian offspring with ACE DD and DI genotypes but not in the II genotype or in Slavic offspring . In the There are several limitations to this study. First, we use a single 24-hour urine collection to estimate dietary salt as previous studies , 39. HowIn the patients with PA, a medium 24-hour UNa level was associated with a lower LVMI compared to a higher or lower UNa level, and the 24-hour UAldo level was positively associated with LVMI.


Chronic fluid overload is common in patients with chronic kidney disease (CKD) and can with time lead to diastolic dysfunction and heart failure. We investigated whether markers of fluid status, such as NT-proBNP and bioimpedance spectroscopy (BIS), can predict echocardiographic findings of diastolic dysfunction in non-dialysis CKD5 patients.BIS, echocardiography, and measurement of serum NT-proBNP were performed in patients with non-dialysis CKD stage 5 at a single study visit. E/e´ ratio reflect mean LV diastolic pressure and a ratio greater than 15 was used as a definition of diastolic dysfunction.Eighty-four patients were analyzed. Forty-six patients (54.76%) had E/e´ ratio ≤15 and 38 patients (45.24%) had E/e´ > 15 (diastolic dysfunction). Patients with E/e´>15 had significantly higher serum NT-proBNP  than patients with to E/e´≤15  and had more overhydration (OH), 5.1 liters compared to 2.4 liters. The cut-off values predicting diastolic dysfunction were found to be 2,797 pg/mL for NT-proBNP and 2.45 liters for OH.Regular monitoring of fluid status by BIS and NT-proBNP can be used to find patient with risk of developing diastolic dysfunction. Treatments to correct fluid overload may reduce the risk of developing diastolic dysfunction and improve cardiovascular outcome in patients with CKD. Diastolic dysfunction is frequently found in patients with chronic kidney disease (CKD) and cardiovascular risk (CV) also increases as kidney function declines . In hemoAssessment and management of volume status is especially important as it can improve hemodynamic stability. Although various methods for assessing volume status including physical examination, chest X-rays, and ultrasonography are available, each method has its limitation. The sensitivity, specificity, and predictive values of laboratory studies such as NT-proBNP vary widely depending on the cut-off value, limiting their clinical utility when used alone. Recently, bioimpedance spectroscopy (BIS) performed at the bedside has gained popularity because it is a non-invasive, quick and relatively affordable method to quantitatively assess the volume status of the patient.We investigated whether NT-proBNP and BIS are associated with the echocardiographic findings of diastolic dysfunction in patients with non-dialysis CKD stage 5.This study included 100 patients who were admitted to our hospital between October 2014 and July 2016 for planning a renal replacement therapy. This is a retrospective cohort analysis of data on BIS, echocardiography, and serum NT-proBNP from this visit. Patients diagnosed with acute kidney injury, malignancy, infection, liver cirrhosis, mitral regurgitation, atrial fibrillation, valvular heart disease, or abnormal LV segmental wall motion was also excluded. Two patients with left ventricular ejection fraction (LVEF) less than 45% were also excluded, as was one patient who showed clear findings of overt diastolic failure. This study was approved by the Institutional Review Board of Yonsei University Wonju Severance Christian Hospital. All participants provided written informed consent prior to the study.0.425× height0.725 (m2). LV internal dimensions, LV wall thickness, and LVEF, measured using the biplane modified Simpson rule, were measured according to the reported recommendations [3×[LVEDD]3)×0.8+0.6, where PWTd and SWTd are the posterior and septal wall thickness at end-diastole, respectively, and LVEDD is the M-mode LV dimension with the short axis view at end-diastole [Echocardiography was performed in the harmonic imaging mode using a 3-MHz transducer and commercial ultrasound system . As recommended by the Heart Failure and Echocardiography Associations of European Society of Cardiology, both conventional and tissue Doppler imaging (TDI) echocardiographic techniques were used for the evaluation of LV diastolic function , 8. Tranndations . LV massdiastole . To corrE/e´ ratio was used to determine diastolic function instead of E/A ratio because the latter is greatly influenced by hemodynamic status. Among the echocardiographic parameters, E/e´ ratio reflects mean LV diastolic pressure, and E/e´ ratio >15 is known to be an indication of diastolic dysfunction , 13. EchTM  was performed prior to any dialysis treatment. BCM utilizes alternating electric currents across 50 different frequencies from 5 to 1000 kHz for the measurement of fluid status. The overhydration (OH) value can be calculated from the difference between the normal expected extracellular water (ECW) and actual measured ECW [Bioimpedance spectroscopy using the BCMured ECW . The valured ECW .All blood samples were collected at the study visit. NT-proBNP was measured using electrochemiluminescence immunoassay (ECLIA) on Modular analytics E170 . The analytical measurement range for NT-proBNP was 5 to 35,000 pg/ml.All analyses were performed with IBM Statistics Package for the Social Science version 23.0 . Descriptive statistics were described in terms of the mean ± standard deviation for continuous variables. Patients were classified into E/e´ ratio >15 and E/e´ ratio ≤15 which represents with or without diastolic dysfunction, respectively. The continuous variables were compared using Two-sample T-test whereas the nominal variables  were compared using Fisher’s exact test. Pearson’s correlation analysis was used to examine correlations between E/e´ ratio and other variables. To assess independent variables associated with E/e´ ratio, we performed a multiple linear regression analysis using variables that correlated with E/e´ ratio with P < 0.05 in the univariate analysis: systolic blood pressure, NT-proBNP, albumin, uric acid, OH/ECW, and ECW/TBW. Finally, we calculated a receiver operating characteristic (ROC) curve to establish cut-off values of OH, OH/ECW, ECW/TBW, NT-proBNP and LAVI that discriminate patients with E/e´ ratio >15 from those with E/e´ ratio ≤15. Statistical significance was defined as P < 0.05.The characteristics of the study population are shown in Fractional shortening and LVEF were not significantly different between the two groups. LAVI was significantly greater with diastolic dysfunction. NT-proBNP, which is known to reflect volume status and LV functional status, was also significantly elevated with diastolic dysfunction. Among the values obtained from BIS, parameters reflecting volume status  were significantly higher with diastolic dysfunction .E/e´ ratio was significantly associated with systolic blood pressure, NT-proBNP, albumin, uric acid, as well as with the BIS factors, OH, OH/ECW, ECW, and ECW/TBW .Multiple linear regression analysis was performed for parameters significantly associated with E/e´ ratio except for OH and ECW due to collinearity. Systolic blood pressure, NT-proBNP, and ECW/TBW were independently associated with E/e´ ratio .ROC curves were drawn for NT-proBNP, ECW/TBW, OH/ECW, and OH to determine the cut-off values predicting E/e´ ratio greater than 15. The area under curve (AUC) and cut-off values were as follows: 0.73 ± 0.05 (P < 0.001) and 2,797 pg/mL  for NT-proBNP; 0.77 ± 0.05 (P < 0.001) and 0.486  for ECW/TBW; 0.73 ± 0.05 (P < 0.001) and 17.28%  for OH/ECW; 0.73 ± 0.05 (P < 0.001) and 2.45 liters  for OH.We previously reported that E/e´ ratio predicted mortality and CV events in CKD with the cut-off values of 14.4 and 13.08, respectively [Several studies have suggested that uremic cardiomyopathy first begins as diastolic dysfunction, which then develops into progressive fibrosis and ventricular hypertrophy. If this is true, aggressive intervention at early stage could prevent the irreversible cardiac remodeling and poor prognosis associated with it. Therefore, simple clinical assessments to diagnose diastolic dysfunction at an early phase is needed , 17. TheWhile NT-proBNP is a clinically valuable biomarker in the diagnosis of heart failure in the general population, it is elevated in CKD patients due to decreased renal excretion . An analet al. reported that LAVI ≥34 ml/m2 distinguished the presence of elevated LV filling pressures (defined by E/e´ ratio >15) with 86% sensitivity and 66% specificity [2 . Multiple linear regression analysis investigating on factors correlated with the E/e´ ratio, found that NT-proBNP and ECW/TBW were independently associated. This suggests that NT-proBNP is associated with diastolic dysfunction while also reflecting volume status [E/e´ ratio >15 is generally accepted to reflect abnormal left ventricle relaxation and left ventricular stiffness . Increascificity . Our resAssessment of volume status in CKD patients has become relatively simple and cheap with the development of BIS. However, it is not widely used in clinical practice and echocardiography is most often first performed when clinical symptoms associated with fluid overload  are already developed. Our results indicate that BIS parameters together with NT-proBNP values could be used to judge whether echocardiographic investigation is warranted . Among tThis study includes several limitations. First, this was a single-center study that included a relatively small number of patients. Also, a full workup on coronary artery disease was not performed, and NT-proBNP values greater than 35,000 pg/mL could not be measured accurately. The duration of diastolic dysfunction could not be analyzed. Despite these limitations, our study excluded patients with LVEF less than 45% and included only patients with stage 5 CKD who had not begun hemodialysis. We also objectively assessed the volume status of the patients at the time of echocardiography with BIS. To our knowledge, this is the first study to have attempted such analysis.Taken together, asymptomatic diastolic dysfunction is common in patients with stage 5 CKD and our results indicate that BIS parameters and NT-proBNP may be used to select patients needing echocardiography investigation. Thus, these measures may help to diagnose diastolic dysfunction needing intervention, such as pharmacological treatment or correction of volume status, and may result in improved echocardiographic parameters and cardiac prognosis.


The role of the left ventricle in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and aggravates many common critical diseases . Several supportive therapies, including mechanical ventilation and fluid management, can make RV dysfunction worse, potentially exacerbating shock. We briefly review the epidemiology, pathophysiology, diagnosis, and recommendations to guide management of acute RV dysfunction in ICU patients. Our aim is to clarify the complex effects of mechanical ventilation, fluid therapy, vasoactive drug infusions, and other therapies to resuscitate the critical patient optimally. The role of the left ventricle (LV) in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and exacerbates many common critical illnesses , pulmonary embolism (PE), inferior acute myocardial infarction, and postoperative cardiac surgery).There is a variety of definitions for acute RV dysfunction (RVD), RV failure (RVF), and right heart failure (RHF) in the literature that must be clarified and not used interchangeably.RHF can be defined by a clinical syndrome due to an alteration of structure and/or function of the right heart circulatory system (comprised from the systemic veins up to the pulmonary capillaries) that reduces the ability to propel blood to the pulmonary circuit and/or high systemic venous pressures at rest or with effort :A, 3:AAcutI > 0.4 ng/mL, troponin T > 0.1 ng/mL) predicts severe RVD. Although evidence of cardiomyocyte death can be seen in the absence of RVD, such patients are at risk for progression to circulatory collapse.Evidence of cardiomyocyte death  is a form of RVD due to an acute increase in RV afterload.Acute RVF is defined as acute RVD plus low cardiac output (CO) and hypoperfusion with the consequent multiorgan dysfunction/failure. RVF occurs when the RV fails to provide enough blood flow to the pulmonary circulation to accomplish adequate LV filling [ filling  . Echocardiographic RVD is present between 30 and 56% of normotensive patients with PE. All-cause mortality rate at 30 days in the patients with confirmed PE was 5.4 to 10%, and in-hospital mortality rate directly attributed to PE was 1.1 to 3.3%, depending on whether it is in-patients versus out-patients registry and the degree of illness –11. Card2O [ARDS is one of the most common entities to challenge the RV. The incidence of acute RVD in ARDS varies from 30 to 56%, depending on the definition criteria of RVD, the severity of lung injury, and ventilatory strategy which is associated with increased 28-day mortality even in the lung-protective mechanical ventilation era and Berlin definition of ARDS –17. BothRV myocardial infarction (RVMI) can be complicated by acute RVD in 30–50% of patients with inferior wall ST-elevation MI. Meanwhile, severe hypotension and low CO are present in 10% on admission in the reperfusion era . The rigAcute RVF is a serious problem after cardiothoracic surgery. It occurs in 0.1% of patients after cardiotomy, in 2-3% of patients undergoing heart transplantation, and in 10–20% of patients needing LV assist device insertion . PH and The extent of pulmonary parenchymal resection (loss of pulmonary tissue) and the preexisting PVD/RVD predict the risk and severity of postoperative RVD in patients undergoing lung resection. Hypoxia, atelectasis, and hypercarbia may precipitate acute RVD .Acute RVD is both common and potentially lethal in critically ill patients. Different clinical entities can produce acute RVF in ICU as a consequence of alterations in one or more of the determinants of RV performance . We will discuss the clinically most important etiologies of acute RVD/RVF:The anatomy and physiology of the RV are both unique and complex and quite different from LV. In contrast to the ellipsoidal shape of the LV, the RV appears triangular and crescent-shaped. Anatomically, RV can be described regarding three components: (1) the inlet, which consists of the tricuspid valve, chordal tendineae, and papillary muscles; (2) the trabeculated apical myocardium; and (3) the infundibulum, or conus, which corresponds to the outlet region . Data frRegarding the myofiber architecture of the heart and according to Torrent-Guasp and other authors, the ventricular myocardium is constituted by a continuous band of muscle that extends from the pulmonary artery root to the aortic root, forming a helical structure with two spirals and delimiting the two ventricular cavities. This myocardial band would be composed of the “basal loop” and the “apical loop.” The basal loop is predominantly horizontal and comprises the right and left segments; the apical loop is predominantly vertical and consists of the descending segment (“left septum”) and the ascending segment (“right septum”) –35.Under normal afterload, RV contraction begins at the sinus (inlet chamber) and progresses toward the conus or infundibulum (outlet chamber) (approximately 25 to 50 ms apart), indicating a peristaltic/asynchronous bellows-like pattern of contraction from apex to base. In contrast, LV contracts in a squeezing/synchronous pattern by twisting and rotational movements from apex to base (likened to wringing a towel) . The RV The low impedance and the high capacitance of the normal pulmonary circulation are reflected in the triangular shape of the RV pressure-volume loop, without distinct periods of isovolumic contraction and relaxation –43. RV eRV mechanics and function can be altered in the setting of either pressure/volume overload and primary reduction of contractility owing to myocardial ischemia . The comThe heart has intrinsic mechanisms to maintain CO to beat-to-beat changes in preload and afterload by a heterometric dimension adaptation described by Starling's law of the heart. Myocardial stretch elicits a rapid increase in developed force, which is mainly caused by an increase in myofilament calcium sensitivity (Frank-Starling mechanism). In the next 10–15 min, a second gradual increase in force takes place (slow force response), increasing the calcium transient amplitude secondary to a cardiac autocrine-paracrine nongenomic mechanism and named homeometric autoregulation described by Von Anrep more than 100 years ago . AlthougAcute adaptation of the RV to PH depends on both the stationary (pulmonary vascular resistance) and the pulsatile  components of afterload . It shouRV systolic impairment and dilation emerge once both myocardial intrinsic adapting mechanisms are exhausted. Several molecular and cellular mechanisms have been proposed in the development of acute RVD secondary to PH. RV wall tension increase leads to the cardiomyocyte stress and injury secondary to ischemia, substrate depletion, and mitochondrial energy metabolism impairment . DiffereThe biochemical and mechanical changes accounting for the transition from acute RVD to failure remain a subject of intense study. Some authors have proposed that acute RV failure begins when the coronary vasodilator reserve is exhausted as a consequence of RV ischemia although it is not possible to discard the concomitant existence of a primary RV failure, related to an overdistension of the ventricle , 59. AnoFinally, RV cardiomyocyte ischemia produces another vicious cycle of increased oxygen demand in the setting of decreased oxygen delivery, leading to circulatory collapse and multiorgan failure .The clinical presentation of acute RVF varies depending on the underlying cause, the presence of comorbidities, and the cardiovascular reserve of the right ventricle-arterial unit. It can occur suddenly or catastrophic in a previously “healthy heart” or in a hidden way, worsening of compensated RVD in the setting of a chronic heart and lung disease. The diagnosis of acute RVF in ICU patients can become very difficult due to the presence of comorbid conditions that may cause organ hypoperfusion even in the absence of RVD .Clinical clues and ECG signs of acute RVD are varied and limited by a low sensitivity and specificity. Therefore, diagnosis typically relies on echocardiography. The ascendance of intensivist-conducted echocardiography has become important not only for early detecting acute RVD in ICU patients but also for monitoring and guiding a rational therapy preventing RVF from occurring.Measurements by two-dimensional echocardiography (2DE) are challenging because of the complex three-dimensional geometry of the RV and sonographic interference from the lungs. While transthoracic echocardiography (TTE) provides adequate imaging in 99% of critically ill patients for diagnosing acute RVD and cardiac cause of shock , transesMultiple views are required to an accurate assessment of RV structure and function. We can resume the following views to be used in ICU patients: the parasternal long and short axis, apical four-chamber, and subcostal four-chamber views on TTE and mid-esophageal four-chamber, RV inflow-outflow, and transgastric short axis views on TEE , 65, 66.RV structural parameters: linear and areas measurements to assess RV dilation (absolute and relative to LV) predominantly at inlet chamberRV functional parameters: predominantly global longitudinal systolic function RV afterload assessment.It is advisable to gather three groups of parameters :RV strucGiven the potential risks of placing a PAC and the availability of bedside echocardiography, the use of PAC is much less common nowadays. In general, invasive monitoring should be reserved for those patients with echocardiographic evidence of severe RVD at risk of acute RVF or patients with established RVF, since we can perform repeated measurements rapidly .2), stroke volume index (<30 mL/m2), and mixed-venous oxygen saturation (SvO2 < 55%) [The usual PAC findings suggestive of acute RVD include an elevated CVP (greater than 20 mmHg), an inverse pressure gradient (CVP > PAWP), and a low cardiac index (<2 L/min/m2 < 55%) , 69.2O, PAWP is higher than LV end-diastolic pressure.One of the challenges of using PAC is the accuracy and precision of PAWP assessment due to the influence of respirophasic effects of mechanical ventilation, end-expiratory versus mean digital measurements, the volume of balloon inflation, and increase extension of zones 1 and 2 (West) , 71. We In summary, combining the use of real-time echocardiographic evaluation bedside with the knowledge of RV physiology is the desirable way to diagnose acute RVD/RVF in ICU patients. PAC might contribute to the monitoring and adjustment of the treatment.Effective treatment of acute RVF requires a skilled multidisciplinary team to rapidly assess and triage the patient. The treatment of acute RVD can be divided into the following bundles: (a) general measures including avoiding increasing RV afterload, decreasing RV contractility and optimization of RV preload, applying an “RV-protective” ventilation strategy, and maintaining sinus rhythm and atrioventricular synchrony; (b) pharmacological treatment with a guided inotropic and vasoactive supports; (c) mechanical circulatory support devices. Real-time monitor with bedside echocardiography assessment and the invasive hemodynamic monitoring remain the most valuable methods to guide a rational therapy of acute RVD/RVF in critically ill patients.The prevention of acute RVF in ICU begins with the identification of high-risk patients, for example, patients with severe ARDS and inferior AMI and patients undergoing cardiac surgery with long cardiopulmonary bypass times and receiving cardiac allografts with either long ischemic time or mismatched in size. Once the severe RVD or RVF is recognized, we have to identify and treat any underlying reversible conditions that are either primarily responsible for (triggering factors) or contributing to the progressive impairment of RV function. volume status is essential for the failing RV, as both hypovolemia and hypervolemia may result in reduced CO. The RV has a flatter function curve than the LV, meaning that there is less change in RV performance over a wide range of filling pressures. When volume overload is present, the use of diuretics or renal replacement therapy is required [Proper management ofrequired . Continurequired . OverdiuWe should be aware of the limitation of the dynamic fluid responsiveness predictors in fluid management whenever RV dysfunction is present. It is well known that the presence of RV failure should be suspected when a patient has significant variations of stroke volume or pulse pressure but does not respond to fluids . HoweverBesides, RV preload requirements differ substantially based on whether afterload is normal or increased. When acute RVD occurs in the setting of increased RV afterload, we should be restrictive with volume management. Increasing blood volume to an already overloaded RV  will not only improve perfusion but also impair CO, aggravating RV dilatation, increasing tricuspid regurgitation and right-sided venous congestion and subsequent underfilling of the LV , all of which will lead to hypoperfusion and multiorgan dysfunction. On the contrary, when acute RVD occurs in the setting of normal pulmonary vascular resistance , we can be more liberal with fluid reposition to maintain CO. Some authors have proposed a mini-fluid challenge  as a safer and rational approach in some clinical scenarios  . mechanical ventilation are to reduce the preload and raise the afterload, which in the setting of acute RVD may be a critical issue. The ventilatory strategy is the main nonpharmacological treatment of the RV afterload through the control of hypoxemia, hypercapnia, acidemia, and inspiratory airway pressure. The main principles of mechanical ventilation for patients with acute RVD include (a) limiting tidal volume and PEEP, therefore limiting plateau (<27 cmH2O) and driving pressures (<18 cmH2O), (b) avoiding hypercapnia (<60 mmHg) and acidosis, and (c) preventing or reversing hypoxic pulmonary vasoconstriction [2/FiO2 ratio could be an indication for proning to unload the RV by recruiting collapsed alveoli without causing overdistention and reducing airway pressure and hypercapnia (“RV-protective” ventilation strategy) [The dominant RV effects oftriction . Additiotrategy) –79.Right atrial contraction contributes up to 40% of RV filling and is more important when the RV compliance is impaired . Appropriate sinus heart rate and rhythm, and the maintenance of atrioventricular synchrony and atrial kick, can be among the simplest methods of maintaining and avoiding RV contractility impairment. Electrical or pharmacological cardioversion for the restoration of sinus rhythm and the placement of a temporary pacemaker if heart block is present should be considered .The pharmacological treatment will be focused on reducing the RV afterload and preserving an appropriate systemic pressure (vasoactive support) and increasing the RV contractility (inotropes drug therapy). The ideal cardiovascular drug for use in acute RVF would be an agent that enhances systemic arterial pressure and RV contractility without raising pulmonary vascular resistance (PVR). In summary, the pharmacological treatment should provide the following properties: (1) a predominant inotropic property, (2) avoiding pulmonary vasoconstriction, preferably vasodilation, and (3) maintaining systemic perfusion pressure  with an adequacy of perfusion  . vasopressor support, the primary objectives are to avoid systemic hypotension, achieving systemic pressure higher than the pulmonary pressure and an optimal PVR/SVR (PVR/systemic vascular resistance) ratio (μg/kg/min) [β1 adrenergic agonism, increasing cardiac index and improving RV-pulmonary coupling in studies of RVD secondary to PH [Regarding thee) ratio . Norepine) ratio . Except /kg/min) . Norepinry to PH , 82. Argry to PH . Phenylery to PH , 84. inotropes. Dobutamine has favorable pulmonary vascular effects at lower doses (<5 μg/kg/min), although it leads to increased PVR, tachycardia, and systemic hypotension at doses exceeding 10 μg/kg/min [The next major goal is to improve RV myocardial contractility by usingg/kg/min . If hypoBoth dopamine and epinephrine are not recommended for tachycardia, arrhythmic events, and an increase in the myocardial oxygen consumption. At moderate-high doses of dopamine, PVR/SVR ratio increases  Table 3Table 3. inodilators (inotropic and vasodilatory properties), both milrinone and levosimendan have been recommended for acute RVD treatment. Milrinone is a bipyridine phosphodiesterase III inhibitor that prevents the degradation of cyclic AMP increasing the intracellular calcium influx such that myocardial contractility improved. Similar to dobutamine, systemic vasodilatation may limit its use. This effect is minimized by the use of inhaled milrinone  is the day before cardiac surgery [Amongilrinone . Milrinoosphates –90. Amonosphates –93. We hosphates . Very reosphates . These nosphates , 96. Ear surgery , 98. How surgery , 100. pulmonary vasodilators may be useful to reduce RV afterload in acute RVD settings particularly whenever pulmonary remodeling is suspected or confirmed. Exclusion of an isolated pulmonary venous pressure elevation is important, as increased transpulmonary flow may precipitate pulmonary edema [Specificry edema . Systemiry edema . PulmonaInhaled NO (iNO) is a potent pulmonary vasodilator at concentrations from 5 to 40 parts per million with a rapid onset of action and very short half-life, making it an ideal agent for management of PH and/or hypoxemia in critically ill patients in whom lowering PAP and improving RV function is paramount  –105. WhiThe use of other currently available pulmonary vasodilators, such as the endothelin receptor antagonists (ERA) and the recently approved soluble guanylate cyclase stimulator, riociguat, should probably be avoided in acute RVF due to concerns about unreliable oral absorption. ERA use in the ICU is limited by the potential hepatotoxicity and riociguat may have significant systemic vasodilator effects, especially under conditions such as sepsis. However, oral pulmonary vasodilators can be useful when patients have become hemodynamically stable, and the medical team is planning to withdraw parenteral or inhalation agents, avoiding the rebound of PH . In geneDespite optimal medical management, some patients fail to improve and require implantation of a mechanical circulatory support device. The RV may exhibit a greater capacity for rapid recovery compared with the LV. Recent literature suggests that 42% to 75% of patients with acute RVF recover hemodynamic and functional status enabling device explantation . The useTwo types of mechanical circulatory assistance have been described in the setting of RVF: (a) RV assist devices (RVAD) and (b) extracorporeal membrane oxygenation (ECMO) . RVAD maThere was a lack of large comparison groups of patients with RVF managed with medical treatment only, RVADs, or ECMO. A prospective study that includes a clear definition of refractory RVF, guidelines for device use, and appropriate control groups is required.We have described general management considerations for critically ill patients with acute RVF. A key principle in the management of acute RVD focuses on determination and treatment of the underlying etiology . We brie RV myocardial infarct (preferably with primary percutaneous coronary intervention) may lead to immediate improvement and later complete recovery of RV function and a better outcome [Early myocardial reperfusion of patients with outcome . Unlike  outcome . So, lat pulmonary embolism. Unless contraindications exist, acute PE is treated with anticoagulation. Based on the contemporary risk classification, “high-risk” patients  and “intermediate-high-risk” patients  if RV dysfunction leads to hemodynamic decompensation, reperfusion treatment, preferably systemic (i.v.) thrombolysis, is recommended [RVF is the principal determinant of early mortality in the acute phase ofommended . Surgicaommended . Pharmacommended . pulmonary arterial hypertension (PAH) are occasionally seen for the first time in the ICU. Possible triggers for acute RVF in patients with PAH should be actively identified, as their presence will impact clinical management. The most frequent causes are infection/sepsis, supraventricular arrhythmias, anemia with iron deficiency, and nonadherence to or withdrawal from chronic PAH treatment. As we previously mentioned, hypoxia and hypercapnia, as well as acidosis and hypothermia, are precipitating factors of RVF by promoting pulmonary vasoconstriction and the further increase of PAP. Positive pressure ventilation should be avoided because it increases RV afterload and the sedatives should be used with caution because they may lead to systemic hypotension [Patients with previously unknownotension . Fluid sotension , 120. Inotension . It is notension .Acute respiratory distress syndrome is the main cause of acute RVF encountered in ICU. Mechanical ventilation can contribute to an uncoupling between pulmonary circulation and the RV, predisposing to the RVF. A protective ventilation strategy with focus on maintaining plateau pressure < 27 cmH2O and partial pressure of arterial carbon dioxide < 60 mmHg, adapting positive end-expiratory pressure to RV function, and considering prone positioning for PaO2/fraction of inspired oxygen < 150 mmHg has been recommended to prevent acute RV failure or ameliorate its complications [ications . noncardiac surgery, perioperative RV failure is most often, although not exclusively, secondary to acute pulmonary hypertension (increased afterload). In cardiac surgery, RV failure is also frequently caused by volume overload, myocardial ischemia, preexisting RV dysfunction, or arrhythmias [Inhythmias .Right-sided valvular diseases have a significant and independent impact on morbimortality. Right-sided infective endocarditis accounts for 5–10% of all cases of infective endocarditis and may occur in native valves (intravenous drug abusers), prosthetic valves, congenital heart defects, and implanted devices  [cemaker) . SurgeryAcute RVD/RVF is seen with increasing frequency in the intensive care unit and causes or aggravates many common critical diseases.Bedside echocardiography assessment and invasive hemodynamic monitoring remain the most valuable methods to diagnose and to guide a rationale therapy of acute RVD/RVF in critically ill patients.General precautionary measures, early diagnosis of RVD, and etiology-specific therapy may reduce the appearance of RVF. Supportive therapies focused on improving RV function via optimization of preload, enhancing contractility, and reducing afterload are the key principles in the management of acute RVF.Future research should focus on better understanding the cellular and molecular mechanisms of acute RV cardiac dysfunction to develop novel therapies that directly target the injured myocardium.