Twenty five patients with myocardial scar or QRS ≤ 150 or the absence of LBBB  underwent acute hemodynamic assessment by LV + dP/dtmax with a variety of LV pacing configurations at an optimized AV delay. The change in LV + dP/dt max (%ΔLV + dP/dt max) with 3P-MPP syn  was neither statistically significantly different to 3P-MPP seq  nor to SPP basal  or SPP mid , but higher than SPP apical . AHR (defined as a %ΔLV + dP/dt max ≥ 10%) varied between pacing configurations: 36% (9/25) for SPP apical, 44% (11/25) for SPP basal, 54% (13/24) for SPP mid, 56% (14/25) for 3P-MPP syn and 48% (11/23) for 3P-MPP seq.Fifteen patients  had an AHR in at least one pacing configuration. AHR was observed in 10/13 (77%) patients with a LBBB but only in 5/12 (42%) patients with a non-LBBB (p = 0.11). To conclude, simultaneous or sequential multipoint pacing compared to single point pacing did not improve the acute hemodynamic effect in a suboptimal CRT response population.The aim of the SYNSEQ  study was to evaluate the acute hemodynamic response (AHR) of simultaneous (3P-MPP ClinicalTrials.gov, identifier: NCT02914457. Cardiac resynchronization therapy (CRT) has transformed the treatment of patients with heart failure, impaired left ventricular (LV) function and a wide QRS complex . It is wsyn) could achieve a more rapid and uniform LV activation than single point pacing (SPP). A better acute hemodynamic response (AHR) to CRT with MPP compared to SPP has been reported by some studies (seq) could also provide a physiological pattern of LV activation  or sequential (3P-MPPseq) MPP pacing. Recent data show that acute hemodynamic response measured by LV dP/dtmax is correlated with better clinical outcome and reverse remodeling, expressed as reduction of LVESV and LVEF improvement  study (NCT02914457) was an acute hemodynamic study with prospective enrolment, conducted across five European centers. All patients provided written informed consent. The study was approved by the Local Ethics Committees and complied with the Declaration of Helsinki.-LBBB. ECG morphology was assessed independently by two blinded investigators. The etiology of heart failure was confirmed on basis of clinical history, and the echocardiographic examination. In addition, transmural/subendocardial myocardial scar was accessed by late-gadolinium enhancement cardiac magnetic resonance , followed by deployment of a quadripolar LV lead within the vein chosen by implanters, who were instructed to deploy the LV lead tip as apical as possible within the vein of choice  and right anterior oblique (30°) fluoroscopic views were used to localize lead positions, as previously described . Briefly) were acquired with a 32-channel recording system  and recorded on a laptop computer using customized software. Beat-to-beat raw signals were visualized and checked in real time to ensure appropriate signal quality and to confirm capture. Experimental lead configurations and atrioventricular (AV) delay settings were digitally annotated for off-line analysis.The acute hemodynamic study was undertaken during implantation of a CRT device. The CRT implantation was performed as per standard practice after completion of the acute study. Four external pacemakers , synchronized by a central master pacemaker  and a custom-made switch box, were used for each pacing site to ensure capture. The atrial channel of the central master was used for right atrial pacing. Throughout the acute study, cardiac electrograms, surface ECGs, invasive arterial blood pressure  and LV pressure  and AV delays of ±30 and ±60 ms around this AV delay. All measurements were repeated 4 times over 20 beats for each pacing configuration and AV delay, interspersed with AAI pacing, to minimize sampling error . The tested LV pacing configurations were RV and SPPapex, RV and SPPmid, RV and SPPbasal, RV and 3P-MPPsyn, RV and MPPseq. For analysis, up to eight beats prior and eight beats immediately after each pacing change from a pacing configuration to AAI pacing were used to calculate percentage change in LV + dP/dtmax.The reference for calculation of %ΔLV + dP/dtng error . The intmax (%ΔLV + dP/dtmax) from pacing on to pacing off (AAI). The acute hemodynamic response (AHR) was defined as ≥10% increase in the acute hemodynamic effect (%ΔLV + dP/dtmax).Acute hemodynamic effect (AHE) was assessed as the percentage change in LV + dP/dtBeat-to-beat LV intraventricular pressure, 12 lead surface ECG and endocardial  electrograms were acquired simultaneously using a 32-channel physiological recording system . Data analysis was undertaken offline. The Raschlab v0.3.0 software package  was used for data review and annotation. Non-captured beats and ventricular ectopic beats plus the subsequent two beats were identified visually and excluded from further analyses. The dataset was then converted to Matlab  compatible format for further analysis.max for up to eight cardiac beats before and after the experimental transition from pacing on to pacing off. We then calculated ΔLV + dP/dtmax for each of the eight transitions.The AHE for each configuration was calculated with the median LV + dP/dtThe paced QRS duration was measured from the ventricular pacing spike to the end of the QRS complex in surface ECGs. The Q-LV interval was defined as the interval from the onset of the intrinsic QRS on the surface ECG to the first large positive or negative peak of the LV electrogram. Q-LV-timing data are expressed as Q-LV/QRS. The electrical delay from RV or LV pacing spike to the different LV activations was also measured.max was calculated for each subject and each configuration by a regression analysis constructing a quadratic curve through all AV-delays  and R (versions up to 3.6.1). Primary objectives: For comparison between pacing configurations, the following approach was performed. Firstly, the maximal average %ΔLV + dP/dtV-delays , 26. SecContinuous variables are expressed as mean ± SD (unless indicated otherwise). No correction for multiple testing was performed because of the exploratory nature of this study.Thirty-one patients were enrolled in the study. Complete datasets were available for analysis for 25 patients , 12 of whom  showed no typical LBBB pattern on ECG. Twenty patients presented with myocardial scar , and 10 had a QRS-duration ≤ 150 . Patients received maximally tolerated pharmacological therapy for heart failure prior to the CRT implant. Patients' demographics are summarized in max for all pacing configurations at the optimized AV delay: 3P-MPPsyn , 3P-MPPseq , SPPbasal , SPPmid , and SPPapical . Comparisons between 3P-MPPsyn and SPP configurations, 3PP-MPPseq and SPP configurations as well as between 3P-MPPsyn and 3P-MPPseq based on the weighted within-patient differences were not statistically significant except for comparison between 3P-MPPsyn and SPPapical  as well as 3P-MPPseq and SPPapical   for SPPbasal, 54% (13/24) for SPPmid, 56% (14/25) for 3P-MPPsyn and 48% (11/23) for 3P-MPPseq. Overall, AHR was similar for MPP configurations and SPP configurations.Fifteen patients  showed an acute hemodynamic response in at least one pacing configuration. Acute hemodynamic responder rates  varied between pacing configurations: 36% (9/25) for SPPmax) trended higher for all pacing configuration in patients with a LBBB. The AHR in at least one pacing configuration was  for patients with a typical LBBB compared to patients with a non-LBBB  (p = 0.11).Patients had a mean QRS-duration of 158.7 ± 11.9 ms, and 52% (13/25) of patients presented with typical LBBB pattern on ECG. As shown in basal (4.9% ± 16.5), SPPmid (3.2 ± 14.9%), SPPapical (8.7% ± 18.0), and MPPseq (8.5% ± 19.7)], but decreased by 4.3% with 3P-MPPsyn (−4.3% ± 14.3). No significant correlation emerged between %ΔQRS duration and %ΔLV + dP/dtmax .Percentage change QRS duration (%ΔQRS duration) increased by 3-9% for most pacing configurations . Our stmax <10%) for any configuration (consistent hemodynamic non-responders). In 24% patients we find an acute hemodynamic response (%ΔLV + dP/dtmax ≥ 10%) independent of the configuration (consistent hemodynamic responders). And finally, in the remaining 36% patients we find an acute hemodynamic response only in some of the tested configurations. This last group is clinically the most relevant one, as choosing the right configuration will make the difference between acute hemodynamic response and non-response and thus result in reversed remodeling of LV and long-term patient benefit . At the same time 3P-MPPsyn demonstrated the highest acute hemodynamic benefit. Moreover, 3P-MPPsyn was the optimal configuration in 47% of those 15 patients who demonstrated an AHR in at least one configuration which was significantly higher than the proportion 21% expected by chance . This indicates that MPP appears to consistently display better hemodynamic response.In the present study, 3P-MPPmax, stroke work, stroke volume and LVEF, compared with the best SPP vector configuration. Thibault et al. also showed that MPPsyn was associated with a higher ΔLV + dP/dtmax than AAI pacing and that MPP was superior to SPP in 72% patients . 3P-MPPseq had similar mean AHE as SPPmid and SPPbasal. An acute hemodynamic effect emerged compared to SPP-apical, which must however be attributed to the relatively lesser effect of SPP-apical stimulation. In normal sinus rhythm, electrical impulses travel through the rapid conduction system from the His bundle toward the apex. Thereafter, LV activation spreads from apex to base as impulses exit the Purkinje system into the slower-conducting working myocardium (max) could be achieved by synchronizing pacing to the earliest activated segment .Collectively the two MPP configurations achieved the highest acute hemodynamic response in 16/25 (64%) patients which was significantly higher than the value (39.2%) expected by chance  followed by left ventricular (LV) pacing [His-Optimized CRT (HOT-CRT)] improves ventricular electrical synchrony beyond BiV and MPP , 44. In syn, which led to a reduction. As in other studies  than observed in patients with LBBB and greater QRS durations   .This study shows that even in patients with a reduced likelihood of response to, a typical LBBB morphology seems still associated with an improved acute hemodynamics. Our findings indicate that tailoring of pacing configurations  is required to achieve an acute hemodynamic effect in individual patients on the borderline of an clinically relevant hemodynamic response. Whilst our findings support the use of MPP as an option in some patients, it has no clear general benefit in the entire potentially predisposed group.The small sample size is an important limitation, especially for the comparison between LBBB and non-LBBB patients. Therefore, other group comparisons like scar and no-scar or QRS < or > than 150 ms were not performed. The current study was a relatively small, but multicenter, non-randomized study. Furthermore, only acute hemodynamic measurements were used to define the optimal CRT device setting resulting in the best CRT-response. The results observed in this study should be tested in a larger cohort including besides acute hemodynamic measurements also longer term echocardiographic and clinical outcomes . 3. Comité Ético de Investigación Clínica (Instituto de Investigación Sanitaria La Fe), Valencia, Spain. 4. West Midlands - Edgbaston Research Ethics Committee The Old Chapel Royal Standard Place Nottingham NG1 6FS. 5. Regionala Etikprövningsn ämden Afdelning 1 Sandgatan 1 22350 Lund Sweden. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that this study received funding from Medtronic, Inc., Bakken Research Center (BRC), Maastricht, The Netherlands. The funder had the following involvement in the study: a role in study design, data collection and analysis (including statistician and database management), decision to publish, preparation of the manuscript and submission process.VS, FLem, and BS were employed by the company Medtronic Inc. BM and RC were an employee of Medtronic and holds Medtronic stocks. MS, AM, AS, and FLey they received fees from commercial companies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Changes in left ventricular (LV) geometry are early manifestations of cardiac damage. The relationship between vascular aging and LV geometry has been reported. However, in newly diagnosed primary aldosteronism (PA), with more severe target organ damage than essential hypertension, the relationship between vascular aging and LV geometry has never been described.We conducted a retrospective study among newly diagnosed PA from 1 January 2017 to 30 September 2021 at the Third Xiangya Hospital. The data of vascular aging parameters were collected, including ankle–brachial index (ABI), brachial–ankle pulse wave velocity (baPWV), and carotid intima-media thickness (cIMT). Echocardiography data were collected to assess LV geometry patterns.A total of 146 patients with newly diagnosed PA were included. The mean age was 44.77 ± 9.79 years, and 46.58% participants were women. Linear regression analysis adjusting all potential confounders showed that cIMT was significantly associated with LV mass index (LVMI)  and baPWV was significantly associated with relative wall thickness (RWT) . Multifactorial adjusted logistic regression analysis demonstrated that cIMT was significantly associated with LV hypertrophy (LVH)  and baPWV was significantly associated with LV concentric geometry (LVCG) .baPWV was significantly associated with LVCG and cIMT was significantly associated with LVH in newly diagnosed PA. This study provides insights on the importance of baPWV measurement and cIMT measurement in early assessment of cardiac damage in newly diagnosed PA. Primary aldosteronism (PA) is defined as increased secretion of aldosterone by the adrenal cortex and suppressed activity of the renin–angiotensin system, which is clinically manifested as hypertension and hypokalemia . The preVascular aging reflects the structural and functional changes of the large conduit arteries . CarotidHowever, in PA, a population at high risk for cardiovascular events, the relationship between vascular aging and LV geometry has never been explored. In the present study, we aimed to investigate the association of the vascular aging parameter  and LV geometry in new diagnosed patients with PA and to provide support for the assessment of target organ injury in the preliminary evaluation of PA.2]; (5) cardiovascular events within the last 6 months, including myocardial infarction or stroke; (6) suffered from cancer and other systemic diseases, including acute or chronic inflammatory diseases; and (7) pregnant or lactating women. The present study was approved by the Medical Ethics Committee of the Third Xiangya Hospital . All the patients signed informed consent at admission and agreed to share their health information for medical research.The study participants were recruited from 1 January 2017 to 30 September 2021 at the Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China. The records of 146 patients with newly diagnosed PA were retrospectively collected in the database of the Third Xiangya Hospital. The inclusion criteria were as follows: (1) age ≥18 years old and (2) confirmed diagnosed with PA on this admission and not previously diagnosed with PA. The exclusion criteria were as follows: (1) missing echocardiography data; (2) simultaneously missing data of baPWV, ABI, and cIMT; (3) a definite diagnosis of other secondary hypertension; (4) serious heart disease  or severe chronic kidney disease [estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m-1/ng·ml-1·h-1), further confirmatory tests were performed to confirm the diagnosis.Before screening and confirmatory tests, antihypertensive medicine with great influence on the aldosterone-to-renin ratio (ARR) was withdrawn at least 4 weeks according to the Endocrine Society’s clinical practice guideline . Patient-1 after the infusion of 2 L of normal saline . PAC was measured basally at 08:00 and after the completion of an infusion of 2 L of normal saline in 4 h, and PA was diagnosed when PAC >10 ng·mll saline . Studiesl saline .Information on sociodemographic characteristics and clinical data were obtained from electronic medical records, including age, gender, height, weight, smoking status , drinking status , serum potassium level, blood pressure (BP), heart rate, the duration of hypertension, a family history of premature cardiovascular disease, and BP-lowing drug treatment. BP measurements were taken in the sitting position after a rest period of at least 5 min using an automated electronic device . The body mass index (BMI) is calculated by dividing the body weight in kilograms by the square of the height in meters. Biochemical parameters included fasting blood glucose (FBG), blood lipid levels , and serum creatinine. The eGFR was calculated using the Modification of Diet in Renal Disease formula .The ABI and baPWV were measured simultaneously with an automatic waveform analyzer . The measurement was taken in the supine position after a rest period of at least 5 min. ABI was measured as the ratio of the systolic BP of the ankle artery to that of the brachial artery. The pulse waves of the brachial and posterior tibial arteries of the left and right limbs were measured to assess the transmission time between brachial and posterior tibial artery waveforms. The baPWV was calculated as the brachial–ankle distance divided by the transmission time . The aveEchocardiography was performed by trained cardiologists using an available machine , according to the recommendation from the American Society of Echocardiography and the European Association of Cardiovascular Imaging . The LV LV geometry patterns were defined into normal, concentric remodeling, concentric LVH, and eccentric LVH. LVH was defined as LVMI >115 g/m² in men and >95 g/m² in women, including concentric LVH (RWT > 0.42), and eccentric LVH (RWT ≤ 0.42). RWT > 0.42 without LVH was considered diagnostic for concentric remodeling. Concentric LVH and concentric remodeling were defined as LVCG.Continuous variables were presented as weighted means ± standard deviation or median (interquartile range) and categorical variables as numbers (percentages). Continuous variables were compared using Student’s t-test or Wilcoxon rank sum test, and categorical variables were compared using chi-square analysis. Spearman correlation analysis was performed to assess the correlation of vascular ageing parameters with LVMI and RWT. The linear regression model was applied to compare the relationship between vascular aging parameters with LVMI and RTW. When the dependent variable was not normally distributed data, we performed logarithmic transformation on the data. When the association of vascular ageing parameters and LV geometry was investigated, logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) by controlling age, gender, BMI, smoking status, drinking status, BP, heart rate, FBG, TG, HDL-C, eGFR, serum potassium level, PAC, the duration of hypertension, a family history of premature cardiovascular disease, and BP-lowering drug treatment. All statistical analyses were performed using Stata version 16.0 . P-value < 0.05 (two sided) was considered to be statistically significant.This study included 146 patients with newly diagnosed PA. The characteristics of these patients are shown in The correlation of vascular parameters with LVMI and RWT is demonstrated in  A crude model showed that ABI and cIMT were positively associated with LVMI and baPWV was positively associated with RWT. After adjusting all potential confounders, cIMT was still significantly associated with LVMI  and baPWV was still significantly associated with RWT .The results of the linear regression analysis of the relationship of vascular parameters with LVMI and RWT are summarized in We compared the values of vascular parameters between LVH and non-LVH and LVCG and non-LVCG. As shown in To the best of our knowledge, this is the first study to explore the relationship of baPWV, ABI, and cIMT with LV geometry in patients with newly diagnosed PA. In the present study, we found that baPWV was significantly associated with RWT and LVCG and cIMT was significantly associated with LVMI and LVH in newly diagnosed PA. The finding of this study provided evidence for the significant contribution of baPWV and cIMT to abnormal LV geometry in newly diagnosed PA.The change of LV geometry is a response to systemic and local hemodynamic changes and has also been described as target organ injury , 23. It In this current study, we analyzed the association of baPWV, ABI, and cIMT with LV geometry in patients with newly diagnosed PA. Our study found that baPWV was positively correlated with RWT; ABI and cIMT were positively correlated with LVMI, which was consistent with previous studies , 28. MorVascular remodeling in patients with PA mainly involves the increase of cells and extracellular matrix in the subintimal space and middle layer, which is manifested by vascular wall thickening, arterial stiffness, and subsequent vascular dysfunction , 36. BaPThis study also has some limitations. First, since this study was retrospective, it could not provide a causal relationship between vascular parameters and LV geometry. Future studies could follow up the effects of increased baPWV or cIMT on LV geometry using a longitudinal design. Furthermore, we used baPWV as the indicator of arterial stiffness, while cfPWV is considered a gold indicator of arterial stiffness . HoweverThe present study suggested that baPWV was significantly and independently associated with LVCG and cIMT was significantly and independently associated with LVH in patients with newly diagnosed PA. This study provides insights on the importance of early baPWV and cIMT measurement in the assessment of LV geometry change in newly diagnosed PA.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was reviewed and approved by the Medical Ethics Committee of the Third Xiangya Hospital. The patients/participants provided their written informed consent to participate in this study.WJ and XL contributed to conception and design of the study. MH and JL wrote the first draft of the manuscript. MH and JL performed the statistical analysis. XZ and SC wrote the sections of the manuscript. All authors contributed to article and approved the submitted version.The study was supported by the Key Research and Development program of Hunan Province (NO.2022SK2029), the National Natural Science Foundation of China Projects (NO.81800271).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Soluble suppression of tumorigenicity 2 (ST2) is closely related to the development of cardiovascular disease, but the level of acute coronary syndrome (ACS) and the relationship between ST2 and ACS are unclear.n = 65) and non‐ST‐segment elevation myocardial infarction (NSTEMI) group (n = 58), and the healthy population, without chest pain and with normal coronary CT, was included as a control group (n = 55). Laboratory index levels were collected from each participant. The baseline information was reviewed and analyzed. The binary logistic regression was used to explore the relation of ST2 levels with the occurrence of ACS and NSTEMI, and the diagnostic performance of ST2 for diagnosing ACS or NSTEMI was evaluated using a receiver‐operating characteristic (ROC) curve.Patients with the acute coronary syndrome were divided into the unstable angina pectoris (USAP) group (p < 0.01). ST2 levels were positively correlated with ALT, AST, and BNP in the control group, were negatively correlated with HGB and TG in the USAP group, and were positively correlated with WBC, GLU, BNP, and Gensini scores in the NSTEMI group. Multivariate analysis revealed that the occurrence of ACS was associated with ST2, BNP, GLU, TC, BUN, WBC, and PLT, and the occurrence of NSTEMI was associated with AST, WBC, LDL‐C, and ST2. Meanwhile, ST2 levels achieved good performance for ACS and NSTEMI diagnostician.The level of ST2 was found significantly higher in NSTEMI than in USAP and was higher in USAP than in control (ST2 could be used as an auxiliary diagnostic indicator for the occurrence of ACS and NSTEMI. The diagnostic performance of ST2 for ACS was equivalent to BNP, and the diagnostic performance of ST2 for NSTEMI was equivalent to AST and WBC. ST2 could be used as an auxiliary diagnostic indicator for the occurrence of ACS and NSTEMI. Despite a variety of therapeutic measures such as emergency thrombolytic therapy, percutaneous coronary stenting (PCI) and coronary artery bypass grafting are now widely used in clinical practice, the risk of major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) remains increasing.The clinical presentation of ACS is typical in only a few cases.Clinical features and electrocardiography provide timely recognition of ST‐segment elevation myocardial infarction (STEMI) and are considered to be the main criteria for the diagnosis of AMI, but not sufficient to diagnose or exclude NSTEMI in the majority of patients.Soluble suppression of tumorigenicity 2 (ST2) is a member of the interleukin 1 receptor family, formally known as interleukin 1 receptor‐like 1 (IL1RL‐1). There are two major isoforms: a transmembrane receptor (ST2L) and a truncated soluble receptor, which can be detected in the serum.22.1The study was reviewed and approved by the Ethics committee of Shanxi Baiqiuen Hospital. Signed informed consent was obtained from the participants before enrollment in the study. 123 patients with ACS (ACS group)  and 55 health screeners with the normal coronary artery (control group)  were included in this study. ACS was divided into two subgroups: USAP, which was defined as a patient with symptoms of myocardial ischemia but no increase in troponin, with or without ischemic changes in the electrocardiogram, such as ST‐segment depression or new T wave inversion, and included 65 patients. NSTEMI was determined as a patient with symptoms of myocardial ischemia and increased in troponin, with ischemic changes in the electrocardiogram, included 58 patients, and all NSTEMI patients were Killip class I. All patients with ACS presented with typical ischemic chest pain within 6 h of symptom onset, without ST‐segment elevation on ECG, and underwent diagnostic coronary angiography. Controls were evaluated by electrocardiogram, echocardiogram, and coronary CT, which showed no abnormalities. The exclusion criteria for all participants were as follows: i) Participants with infections, tumors, or systemic immune diseases; ii) who with severe liver and kidney diseases; iii) patients with severe hypertension with uncontrolled blood pressure, and diabetes mellitus with long‐term uncontrolled blood sugar within the ideal range; iv) who with more than moderate valvular disease, heart failure, hypertrophic cardiomyopathy, thyroid disease, severe anemia; v) patients use of immunosuppressive drugs.2.2Participants were asked to complete a questionnaire on medical history, medication use, height, and weight. All participants underwent chest radiographs, abdominal ultrasonography, electrocardiography, and echocardiography. Left atrial diameter (LAd) and left ventricular end‐diastolic dimension (LVEDD) were measured, and left ventricular ejection fraction (LVEF) was calculated by the Simpson's biplane method.Coronary angiography was performed in all patients with ACS, and the degree of stenosis in the left main coronary artery, the left anterior descending branch, the left rotating branch, and the right coronary artery was assessed in conjunction with the imaging findings. A lesion was considered normal if there was no abnormality or if the stenosis was <50%; a single‐branch lesion was determined if ≥50% stenosis was present in any of the above arteries, and a multi‐branch lesion was determined if ≥50% stenosis was present in two or three arteries. According to the American Heart Association's Gensini score, stenosis ≤25% was scored as 1, 26%–50% as 2, 51%–75% as 4, 76%–90% as 8, stenosis 91%–99% as 16, and complete occlusion as 32, and the final Gensini score was obtained by multiplying the stenosis score of the artery being evaluated by the correlation coefficient. The GRACE score is a tool that can assess the risk and prognosis of ischemic adverse events in patients with CHD, including age, systolic blood pressure, pulse rate, and blood creatinine. The sum of the scores of each index is the GRACE score. 0–109 is considered low risk, 110–140 is considered the intermediate risk, and 141 and above is considered high risk. The TIMI risk score is a simple prediction scheme to classify the risk of death and ischemic events in patients with USAP/NSTEMI.Venous blood is usually collected within 6 h of admission, prior to angiography and administration of medication, and centrifuged at 3000 rpm for 10 min at 4°C to separate plasma and serum. Plasma and serum were aliquoted in Eppendorf tubes and frozen at −80°C until analysis. ST2 was measured using an ST2 assay kit . The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (sCr), uric acid (UA), blood glucose (GLU), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), and brain natriuretic peptide (BNP) were determined using the automatic biochemical analyzer . White blood cells (WBC), hemoglobin (HGB), and platelet (PLT) were measured by an automatic blood cell analyzer .2.3U test was used for the intergroup comparisons. Mean ± standard deviation (SD) or median (quartiles) was used for the presentation of the results. Chi‐square (χ2) tests were used for ratio comparisons intergroup. Fisher exact tests were used when the expected count was <5. The Pearson's or Spearman correlation analysis was used to confirm the association between the variables. The binary logistic regression analyses were used to analyze the relationship between the ST2 levels and other important factors associated with the ACS or NSTEMI (p ≤ 0.05) in the multivariate analyses using stepwise selection. Receiver Operating Characteristics (ROC) curves and area under ROC (AUROC) were used to predict the occurrence of ACS or NSTEMI. The cutoff value of ST2 was determined by the nearest integer (Youden index). The two‐tailed test was set at a significance level of 0.05.SPSS 22.0 software (IBM Corp.) was used for the statistical analyses. T‐test or Mann–Whitney 2.4The sample size was calculated using G power version 3.0.10. The minimum sample size of patients needed to get a power level of 0.80, an alpha level of 0.05, and a medium effect size of 0.50 for ST2 was 52 in each group.33.1p < 0.05 or p < 0.01). The levels of LVEDD in the NSTEMI subgroup were much higher (p < 0.05), and the level of LVEF was notable lower (p < 0.01) compared with the USAP subgroup, and there were more males than females in the NSTEMI subgroup (p < 0.05). Levels of Grace scores, TIMI scores, and Gensini scores were much higher than the USAP subgroup (p < 0.01), and most of the ECG parameters were significantly different in the UA and NST groups (p < 0.05 or p < 0.01). (Table The characteristics of the participants were shown in Table 3.2p < 0.01). The concentrations of ST2, cTnI, ALT, AST, sCr, WBC, LDL‐C, and BNP in the NSTEMI subgroup were much higher than in the USAP subgroup (p < 0.01 or p < 0.05). , AST , and BNP  in the control group. And there were negative correlations between ST2 and HGB , TG  in USAP. For NSTEMI, there were correlations between ST2 and WBC , GLU , BNP , and Gensini score  (Table p < 0.01), BNP , GLU , TC , BUN , WBC , and PLT  were the independent factors for the development of ACS (Table p < 0.05), AST , WBC , and LDL‐C  were the independent factors for the development of NSTEMI . BNP, GLU, TC, BUN, WBC, and PLT were the other independent factors, whose AUC were 0.859 , 0.739 , 0.292 , 0.722 , 0.739 , and 0.268 , respectively (Table p < 0.001). AST, WBC and L‐DLC were the other independent factors, whose AUC were 0.869 , 0.783 , and 0.609 , respectively  is one of the major fatal and disabling diseases affecting millions of people worldwide. ACS leads to compromised diastolic function and myocardial ischemia,Platelets and the coagulation system are key factors in the initiation, amplification, and perpetuation of ACS.In addition, we found that levels of BUN were significantly higher in ACS than in controls. It may be related to the fact that the sympathetic and renin‐angiotensin systems are activated when ACS occurs, and the increase in reabsorption in the proximal renal tubule leads to an increased concentration of BUN.AST is found in large numbers in the heart muscle cells and liver. When the supplement of blood is reduced, a large amount of AST in the cytosol enters the bloodstream, resulting in a significant increase in AST levels, and therefore, AST is used as an adjunct to epicardial coronary artery disease or liver disease. Liver insufficiency is common in heart disease, elevated AST is associated with an increased risk of cardiac‐related death if no other cause of liver damage is found.Cardiac fibrosis after myocardial infarction is one of the common clinical types of myocardial fibrosis, and the core pathology is that the main effector cells of myocardial fibrosis after myocardial infarction are induced by pro‐fibrotic factors such as oxidative stress and inflammatory factors, which leads to changes in biological behaviors such as proliferation, phenotypic differentiation, migration, and secretion, resulting in massive deposition of extracellular matrix, cardiac remodeling, and fibrosis, affecting cardiac diastolic function and electrical signal. It also leads to heart failure and arrhythmias, and affects prognosis.The Gensini score is a scale that reflects the degree of coronary artery stenosis in subjects and is widely used in clinical practice. In the study, we found that ST2 level was positively correlated with the Gensini score, which suggested that ST2 levels in NSTEMI patients were related to the degree of coronary artery stenosis.In addition, we found there was a limited association between ST2 and cTnI, which suggested that the biological behavior of myocardial fibrosis and myocardial infarction are not synchronous after ACS.ROC curve analysis shows that ST2 has good diagnostic efficacy for ACS as well as NSTEMI, even after adjusting for age, gender and BMI. When ST2 is higher than 7.15 ng/ml or 19.6 ng/ml, it means the occurrence of ACS and NSTEMI, and this was different from the cutoff value for heart failure.This study has some limitations. On the one hand, stable angina was not included in this study because it has been studied in many reports, and the relationship between controls and unstable angina has been clarified. On the other hand, although ST2 could reflect the degree of myocardial fibrosis and differentiate between USAP and NSTEMI, it is only used as a diagnostic indicator in the early stages of disease onset and the prognosis of patients is not yet known. Therefore, in future studies, we will continue to return to investigate the efficacy of ST2 on the prognosis of patients.The authors declare that they have no competing interests.


Right ventricular remodeling has been neglected in patients with arterial hypertension as all studies have concentrated on the left ventricle and left atrial-ventricular and ventricular-arterial coupling. The development of novel imaging techniques has revealed significant impairment in the RV structure, systolic and diastolic function, and, afterwards, RV longitudinal mechanics. However, these changes are subclinical and can be detected only after comprehensive imaging analysis. The latest findings confirm the importance of RV hypertrophy, systolic, and diastolic dysfunction in the prediction of cardiovascular adverse events in the hypertensive population, representing an important clinical implication of these parameters. In clinical practice, 2D echocardiography is widely used for the evaluation of RV remodeling. However, existing techniques are largely underused and limited to a few basic parameters (RV thickness and TAPSE), which are not nearly enough for a detailed assessment of RV remodeling. In addition, 3D echocardiography provides the possibility of accurate evaluation of RV volumes and ejection fraction, which are comparable with results obtained by cardiac magnetic resonance (CMR)—a gold standard for the evaluation of the RV. The use of 3D echocardiography is limited due to its low availability, the lack of adequate software necessary for the calculation of results, and the necessity for a higher level of expertise. CMR provides all information required for a detailed assessment of RV structural, functional, and mechanical remodeling, and it is considered the reference method for this type of evaluation. Furthermore, it is the only technique that may provide tissue characterization and evaluation of the interstitial space, which is essential for hypertensive heart disease. The aim of this review is to provide the current level of evidence regarding RV remodeling in patients with arterial hypertension evaluated with different imaging techniques and various parameters from each method. The right ventricle (RV) has long been considered unessential in patients with arterial hypertension. In patients with other conditions that are directly or indirectly involved with the RV, the importance of this cardiac chamber has already been well established, and assessment is provided in everyday clinical echocardiographic or CMR examinations. Nevertheless, studies published in the last decade have revealed the involvement of the RV in patients with arterial hypertension, including functional and mechanical changes, but also structural remodeling that has never before been related to arterial hypertension ,2,3.RV remodeling seems to follow changes on the left side, which means that subtle mechanical changes and diastolic dysfunction occur at the very beginning, while RV hypertrophy and subclinical impairment in systolic function come afterwards. These changes are important as they have been proven to be the independent predictors of cardiovascular and overall mortality in the general population as well as some specific groups of patients ,5,6.The imaging and assessment of different aspects of RV remodeling are challenging and have been long limited to 2D echocardiography, which enables only the basic parameters regarding RV structure and function. There are a couple of reasons for this. First, the anatomical position of the RV in the chest and the relationship with surrounding anatomical structures, as well as its specific crescent shape, do not facilitate the visualization and evaluation of all segments. The development of new techniques within 2D echocardiography, such as speckle tracking imaging, and the introduction of new imaging modalities, namely, 3D echocardiography and cardiac magnetic resonance (CMR), significantly increased our ability to assess the same parameters that are available for the LV. The huge scientific development in the imaging of the RV, achieved in the last decade, opened Pandora’s box and imposed the question of the clinical relevance of all parameters that we can measure nowadays. The current review article summarizes the current clinical and scientific approach in the assessment of RV structure, function, and mechanics in patients with arterial hypertension, which is an important but often neglected topic.Arterial hypertension is characterized by the overstimulation of the sympathetic system and the renin–angiotensin–aldosterone system (RAAS) as well as oxidative stress and endothelial dysfunction, all of which may induce impaired vascular relaxation ,8,9. RAAthe lion of the right ventricular function” and it is already known that the septum contributes to approximately 30% of RV systolic function [Ventricular interaction is another important reason that explains RV remodeling in arterial hypertension, as hemodynamic changes are transferred from the LV to the RV through the interventricular septum. Buckberg et al. called the septum “function . TherefoSome reports have revealed increased pulmonary pressure in patients with arterial hypertension. This can be explained by several mechanisms: (i) the transmission of increased systemic pressure in hypertensive patients combined with the elevation of pulmonary microvascular resistance; (ii) the retrograde transmission of impaired LV relaxation, diastolic dysfunction, and hemodynamic changes. This increase does not usually lead to the development of pulmonary hypertension that would be diagnosed by echocardiography but to an increase in pulmonary pressure compared with normotensive controls.The RV differs from the LV by several anatomical features: pronounced trabeculation, a muscular strand that connects the interventricular septum to the anterior papillary muscle called a moderator band, and a lack of fibrous continuity between its inflow and outflow valves. It has helical fibers distributed into epicardial and endocardial layers, which perform torsion and provide more effective RV systolic function. However, the RV does not have a middle layer and, therefore, relies more on the RV longitudinal shortening than the LV. Even though the interventricular septum is considered a part of the LV, it also includes longitudinal fibers that belong to the RV. It is clear that fibers from different layers in the LV and RV strongly interact and provide effective biventricular function.A recently published study has investigated macroscopic and microscopic differences in the RV structure between hypertensive patients and controls . The autEchocardiographic studies showed significantly higher RV wall thickness in patients with arterial hypertension than in controls , which wOn the other hand, 2D and 3D echocardiographic studies showed a direct correlation between systolic blood pressure and RV wall thickness in hypertensive patients as well as a relationship between systolic blood pressure and RV dilatation, confirming the negative impact of arterial hypertension and even prehypertension on RV remodeling ,20,21. TCMR studies revealed significant changes in interstitial myocardial tissue not only when using conventional techniques such as late gadolinium enhancement ,23; evenRV functional changes in arterial hypertension are usually subclinical but detectible with sophisticated imaging methods. This remodeling considers systolic and diastolic dysfunction. Conventional parameters of RV systolic function  normally do not reveal any impairment in systolic function in hypertensive patients. On the other hand, pulsed and tissue Doppler parameters of RV diastolic function often reveal diastolic dysfunction in hypertensive patients. The most relevant point is which imaging technique (echocardiography vs. CMR) as well as which method within a technique  should be used for the evaluation of RV function. The sensitivity, specificity, and reproducibility of the diverse techniques are different, and it is not difficult to understand the variations in results between studies.Most of the published data showed no difference in conventional 2D echocardiographic parameters  between hypertensive and normotensive subjects ,26,27. HThe evaluation of RV diastolic function is not widely used in clinical practice as its clinical implications have been insufficiently investigated, and the guidelines are not as clear as for LV diastolic dysfunction. Parameters used in the evaluation of RV diastolic function are obtained by pulsed and tissue Doppler. Results from different echocardiographic evaluations are conflicting. Some authors found significantly impaired tricuspid E/A and E/e’ ratios in hypertensive patients ,28,29,30The right atrium (RA) is enlarged in hypertensive patients, and our study showed that the phasic function is significantly influenced by systemic BP . RA phasCurrently used echocardiographic techniques do not provide the same comprehensive evaluation of RV mechanics that is available for the LV. RV mechanics evaluation is normally limited to longitudinal strain, whereas circumferential and radial strain rates are available only in CMR-derived analyses. Moreover, 3D echocardiographic evaluation of RV mechanics, providing data on longitudinal, circumferential, radial, and area strain rates, is available from a limited number of vendors (Toshiba), and the data are scarce and limited to patients with pulmonary hypertension . LongituThe speckle tracking-derived RV longitudinal strain has been the only method used in the last decade A, whereaEarly findings revealed that the free wall RV longitudinal strain was gradually reduced with systolic BP . The samPatients with comorbidities such as obesity, diabetes, and metabolic syndrome had worse RV GLS than patients with isolated hypertension ,37,38,39Data regarding CMR-derived RV GLS are scarce, and one study reported significantly lower RV GLS in diabetic patients with and without arterial hypertension compared with controls, but there was no difference between diabetic patients with and without diabetes .RA longitudinal strain is also significantly decreased in hypertensive patients compared with controls ,21. It iRA phasic function, determined by different segments of the longitudinal strain curve, showed impairment that correlated with systolic BP. Strain-derived RA phasic function is faster, easier, and more reliable and reproducible than volume-derived RA phasic function and, therefore, might be easily used in clinical practice and not only for research purposes A. RA strThe evaluation of RV remodeling is challenging, even with new imaging modalities, but it is significantly improved and provides more comprehensive information than only a decade ago. Conventional echocardiography should be used for the evaluation of RV structure (thickness), systolic parameters , diastolic dysfunction , and RA evaluation (volumetric-derived phasic function). Our recent longitudinal study showed that RV hypertrophy, RV systolic dysfunction, RV diastolic dysfunction, and RA dilatation were correlated with adverse cardiovascular events in the hypertensive population during a 9-year follow-up . HoweverSpeckle tracking echocardiography has opened a new era in RV and RA imaging as it is a convenient, reasonably fast, and reproducible method that provides not only information about the current status of right heart mechanics but has an important predictive value in a large number of cardiovascular conditions ,44. TherNew imaging modalities have revealed a significant involvement of the RV and RA in patients with arterial hypertension. Even though these changes are subtle and subclinical, they are related to adverse outcomes in hypertensive patients, and this is why they should be diagnosed in a timely fashion and regularly followed. RV longitudinal strain should be included in the clinical reports of patients with arterial hypertension as it provides comprehensive information about RV systolic function and mechanics and has important predictive value. Larger studies that include hypertensive patients with longer follow-up periods are warranted to demonstrate the clinical utility of RV (and RA) GLS in this population of patients.


Methamphetamine-associated cardiomyopathy (MA-CMP) is an increasingly recognised aetiology of cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a specialised cardiac imaging modality commonly used in assessment of cardiomyopathy. We aimed to identify specific CMR features associated with MA-CMP.A retrospective cohort study of CMR scans was performed in a single centre between January 2015 and December 2020. Thirty patients with MA-CMP who had undergone CMR were identified. MA-CMP was defined as those with a history of significant methamphetamine use hospitalised with acute decompensated heart failure (other causes of cardiomyopathy excluded). A retrospective analysis of index admission CMRs was performed. All studies were performed on a 1.5 T CMR scanner.The mean age of MA-CMP patients was 43.7 ± 7.5 years, and 86.7% were male. The mean left ventricular (LV) volume obtained in this cohort was consistent with severe LV dilatation (LV end-diastolic volume (334 ± 99 ml); LV end-systolic volume: 269 ± 98 ml), whilst the right ventricular (RV) volume indicated moderate-to-severe dilatation . Mean LV ejection fraction (20.9 ± 9.2%) indicated severe LV dysfunction, with moderate-to-severe RV dysfunction also detected (RV ejection fraction: 29.4 ± 13.4%). 22 patients (73.3%) had myocardial late gadolinium enhancement (LGE), of which 59.1% were located in the mid-wall, with all of these involving the interventricular septum. 22.7% displayed localised regions of sub-endocardial LGE in a variety of locations, and 18.2% had transmural regions of LGE that were located in the inferior and inferolateral segments. 6 patients (20%) had intracardiac thrombus .MA-CMP was associated with severe biventricular dilatation and dysfunction, with a high prevalence of intraventricular thrombus. This cohort study highlights that MA-CMP patients have a high prevalence of CMR findings. The growth in methamphetamine usage worldwide continues to present increasing societal and healthcare challenges. With the escalation of its usage in a variety of social demographics, methamphetamine-associated cardiomyopathy (MA-CMP) has become an increasingly recognised aetiology of cardiomyopathy, particularly amongst younger patients presenting to emergency departments with heart failure (HF) symptoms and are found to have newly detected ventricular dysfunction –4. The cAlthough there has been a number of observational studies of this cohort , 5, 7–10A retrospective cohort study was performed of a population of patients with MA-CMP. Patients were identified at the Central Adelaide Local Health Network , via a search of the HF database and searching through discharge summaries, utilising electronic medical records from the period between January 2015 and December 2020, to identify all patients with MA-CMP. MA-CMP was defined as those with a history of regular, long-term methamphetamine use, who had required inpatient cardiology admission with acute decompensated HF and had no other identifiable causes of cardiomyopathy. Specifically, coronary artery disease, primary valvular disease , active hyperthyroidism, idiopathic, viral, alcohol, chemotherapy or hypertension-related cardiomyopathy were excluded where identified. If there was a history of alcohol or other significant drug use, it was assessed whether methamphetamine was the primary drug of dependence for participant inclusion. Patients were also excluded if they had no available CMR imaging, including those that could not tolerate CMR due to contraindications and/or claustrophobia. All studies were performed on a 1.5 T CMR scanner  with Gadovist , the administered intravenous contrast agent.Clinical and demographic data collected included age at time of index admission/diagnosis, sex, ethnicity, known route of methamphetamine ingestion, duration and/or cessation of methamphetamine use, use of tobacco products, excessive alcohol consumption, and other drug abuse, as well as medical comorbidities . Therapies patients were receiving for MA-CMP were also recorded along with patient compliance. CMR parameters collected included: LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), right ventricular (RV) end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV ejection fraction , presence and location of late gadolinium enhancement (LGE) and presence of intra-cardiac thrombus, according to published standards .All continuous variables were presented as mean ± SD as appropriate to distribution. Categorical variables were expressed as number and percentage. Outcomes which did not follow the normal distribution, as assessed via plotting, were expressed as mean and range, with means tested using Mann–Whitney U. For all tests, significance was accepted as a p value < 0.05. All statistical analyses were conducted using SPSS . The CALHN Human Research Ethics Committee of the Royal Adelaide Hospital approved the study protocol and waived informed consent.A total of 4,700 consecutive patients with a history of HF were identified during the study period. After exclusion criteria were applied, 30 patients were included in the cohort. Cohort selection flowchart is shown in Fig. The year of diagnosis was recorded with an increase in incidence evident across the data collection period, both within the population with CMR imaging performed, and those without, as seen in Fig. Table Many MA-CMP patients had concurrent heavy tobacco use (80%), and a portion had a previous or current history of excess alcohol use (40%) and/or marijuana use (50%). Comorbidities were present within the cohort, with overall 33.3% possessing a history of hypertension, 10% diabetes mellitus, 10% hyperlipidaemia, 3.3% chronic kidney disease and 3.3% with prior ischaemic heart disease. No patients had a history of cardiac rhythm disorders.CMR parameters are presented in Table Table Six patients (20%) had intracardiac thrombus. Of these cases, 66.7% were in the LV and 33.3% were biventricular. Figure Follow-up data were available on 24 of the 30 patients (80%) included in this cohort using echocardiography. Complete cessation of methamphetamine use and compliance to HF pharmacotherapy was advised to all included participants in this cohort during their index admission. Of the cohort of 11 patients who ceased methamphetamine, all (100%) complied with their medication regime. This compared with only 5 out of the 13 patients taking prescribed medications who continued to use methamphetamine following diagnosis. Over a median follow-up of 6 months (IQR 3.0 to 6.5 months) from index admission, improvement in cardiac function, specifically a LVEF increase of > 5%, was observed in participants who achieved complete cessation of their methamphetamine use compared to those who reduced or remained consistent in their consumption . The presence of baseline LGE on CMR, however, did not show a significant impact on change in follow up LVEF. Additionally, whilst there were variable cessation rates in both patients with and without LGE, a two-way ANOVA test indicates that only cessation is statistically significant , independent of LGE. These figures are presented in Tables Given the potential of alcohol abuse being a confounder and contributor to cardiomyopathy in this population, the relationship of alcohol abuse on ventricular volumes, LVEF and RVEF (at baseline), as well as recovery in ventricular function was measured. Whilst there was a small trend to increased volumes in those with a history of alcohol abuse Table , this waCMR has evolved as an essential investigative tool in evaluation of cardiomyopathy due to its accurate quantification of biventricular volumes and ejection fraction as well as tissue characterisation . In addiLV dilation and contractile impairment is a significant predictor of adverse outcomes in dilated cardiomyopathy . In addiThe mechanisms of ventricular dilatation specifically in MA-CMP warrant discussion. MA-CMP development is postulated to be a secondary to an interplay of direct and indirect mechanistic pathways. Directly, amphetamines promote free radical production resulting in direct cellular injury, apoptosis via increased p53 activity, mitochondrial dysfunction, altered gene expression and defective intracellular haemostasis. Contractile dysfunction develops from disrupted electrical–mechanical coupling . In suscLGE is an effective, well-validated and reproducible method of detecting myocardial fibrosis and other pathologies such as infarction, infiltration and inflammation. An abundance of CMR clinical studies have demonstrated correlation with adverse events . However, patients included were assessed on review of the medical records as to what was their predominant drug of abuse and dependence. Patients only with predominant MA abuse were included in our study, but alcohol certainly may have been a contributor to development of a cardiomyopathy in those with a history of alcohol abuse which does represent a potential confounder to the findings reported. Importantly, there was no statistically significant difference in the baseline ventricular volumes in those with previous alcohol abuse, compared to those who did not.The population selected for this cohort had a significant and long-history of methamphetamine abuse. However, the intensity of methamphetamine use is difficult to quantify in this patient population, particularly when clinical data is retrieved retrospectively from reviewing electronic medical records. Therefore, the study does represent a reasonably heterogenous population of methamphetamine users, with variable methods and levels of consumption.To our knowledge, this is the largest series of MA-CMP that has been characterised with CMR. This study demonstrated that MA-CMP is associated with significant biventricular dilatation and systolic dysfunction, a high incidence of LGE and a 20% incidence of intra-cardiac thrombus, which was sometimes biventricular. The MA-CMP population possessed heterogenous patterns of LGE detected, most frequently observed in the mid-wall and interventricular septum. Follow-up data of this cohort revealed that abstinence from methamphetamine use following diagnosis of MA-CMP was associated with a greater improvement in LVEF. Future studies with larger cohorts, as well as outpatient cohorts, are required to corroborate these findings and to investigate their follow-up imaging for further recovery of cardiac function.


Cardiogenic shock complicating acute myocardial infarction is a complex clinical condition associated with dismal prognosis. Routine early target vessel revascularization remains the most effective treatment to substantially improve outcomes, but mortality remains high. Temporary circulatory support devices have emerged with the aim to enhance cardiac unloading and improve end-organ perfusion. However, quality evidence to guide device selection, optimal installation timing, and post-implantation management are scarce, stressing the importance of multidisciplinary expert care. This review focuses on the contemporary use of short-term support devices in the setting of cardiogenic shock following acute myocardial infarction, including the common challenges associated this practice. Cardiogenic shock (CS) is the leading cause of death in acute myocardial infarction (AMI), and it is characterized by tissue hypoperfusion and hypoxia related to low cardiac output . It is oNationwide databases examining temporal trends in CS have shown inconsistent data regarding the incidence of CS. While some studies demonstrate an increase in the overall incidence of CS in recent years , others CS complicates approximately 5–10% of AMI’s with a higher incidence in ST elevation myocardial infarction (STEMI) and is more frequently seen among women and patients > 75 years old ,6.The clinical and hemodynamic heterogenicity of CS with only few randomized clinical trials evaluating the various therapeutic approaches and recommendations lead to uncertainties as to the best treatment strategies. Thus, management of CS is often challenging and requires early diagnosis and institution of high-quality interdisciplinary care . When trSupportive pharmacologic and device-based therapies are also frequently utilized with little evidence of benefit . Hence, This review is aimed to outline the current evidence of MCS utilization during CS in the setting of AMI and to give future perspective of trials and approaches to treat CS complicating AMI. Other important and crucial treatments for CS complicating AMI are beyond the scope of this review.−1·m−2 AND pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg) . Fi. Fi14]. Similar to patients with CS in the setting of AMI, patients with chronic heart failure (HF) may also require mechanical support due to clinical deterioration with evidence of end-organ hypoperfusion.The INTERMACS  scale helps to stratify patients with advanced HF into seven clinical profiles according to hemodynamic status and level of target organ damage to facilitate the appropriate matching of a patient’s profile with therapeutic options, particularly in relation to potential populations for mechanical circulatory support. INTERMACS profiles 1–3 are associated with the highest level of clinical compromise and mortality rates and thus require temporary device support .p = 0.027 and 47% vs. 34%; p = 0.025, respectively). Thus, in the current era, the only intervention with proven mortality benefit in CS complicating AMI is early revascularization either with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) surgery with class I indication in contemporary guidelines [The current management recommendations of CS are based on early revascularization along with general supportive measures, such as fluids and oxygenation, vasopressors and inotropes, and the use of temporary mechanical support devices . Early ridelines .At present, the impact of inotropic and vasoactive agents on CS outcomes remains controversial . In the MCS is a relatively new option for treating CS complicating AMI and may offer significant advantages over drug therapy, including targeted cardiovascular support without increased risk of myocardial ischemia, possible reduction of myocardial oxygen demand, and avoidance of systemic adverse events .While CS patients in SCAI stages A and B can proceed directly to the catheterization lab for early reperfusion, patients in stages C–E may require initial hemodynamic and/or respiratory stabilization with the shortest possible delays before target vessel revascularization . UnfortuThe main goals of temporary MCS devices are to improve cardiac output by reducing intracardiac filling pressures; reduce left ventricular LV volumes, wall stress, and myocardial oxygen consumption; and ameliorate coronary perfusion to improve tissue perfusion.MCS devices are designed to provide either a temporary, short-term cardiac output support or a long-term assistance to the left and/or right ventricle. Short-term percutaneous platforms are widely used in the setting of CS, in particular in patients refractory to medical therapy, either alone or in combination. Temporary devices may serve as a bridge to recovery or until further decisions in management are made (bridge to decision), such as the need for long-term support, heart transplantation, or destination therapy. Short-term MCS is increasingly used as a bridge to decision in patients with refractory cardiogenic shock . In a meRecent studies have shown that standardized approach to CS, including early target vessel revascularization along with early use of MCS along with close monitoring of hemodynamic parameters and markers of target organ perfusion, may improve outcomes ,24. HoweOptions for acute MCS  include Intra-aortic balloon pump (IABP) counter-pulsation is one of the earliest types of short term MCS. It consists of a flexible 30–50 cc helium-filled balloon catheter (7–8F), inserted percutaneously via the femoral artery, connected to a mobile console that times periodic balloon inflation and deflation according to the cardiac cycle. When inflated in diastole , diastolic and mean arterial pressure rise, thus theoretically improving coronary flow and myocardial oxygenation. On the other hand, when rapidly deflated just prior to blood ejection from the LV, it provides immediate systolic blood pressure attenuation and consequently afterload reduction, leading to an increase in stroke volume. Overall, myocardial oxygen demand is reduced .IABP has been investigated in multiple clinical scenarios, including high-risk PCI and CS in the setting of AMI ,29,30. OAccordingly, the routine use of IBAP was given a class III indication for CS complicating AMI in the STEMI European guidelines . MoreoveIn summary, there is no convincing evidence to support routine use of IABP in post-MI CS patients. Consequently, the overall use of IBAP in the management of ischemic CS is consistently decreasing, with the exception of CS due to severe mitral regurgitation, where the use of IABP is still rated as IIa indication ,6,35.Impella  is a temporary VAD frequently included in the management of patients with post-AMI CS and as a support measure in PCI for high-risk patients ,37. The The safety and feasibility of the Impella 2.5 and CP devices have been reported in large registries . ImpellaThe Impella RP (right percutaneous), introduced via the femoral vein, supports the RV. It is utilized to maintain blood flow from the inferior vena cava into the pulmonary artery with peak flow rate > 4 L/min. The RECOVER RIGHT (The Use of Impella RP Support System in Patients With Right Heart Failure) study was the first to suggest the feasibility and safety of the RV support device in selected patients with RV failure . NeverthWhile the use of IBAP is declining, the use of MCS remained relatively constant, indicating an increase in uptake of other LV support device, in particular Impella . For insThe TandemHeart system  is a percutaneous ventricular assist device that unloads the failing LV by continuously delivering up to 5 L/min of oxygenated blood directly from the left atrium (LA) into the arterial system using a centrifugal pump. The LA is accessed via transeptal approach and device installation requires fluoroscopic guidance and an operator familiar with transeptal access. Creating this LA to femoral artery bypass reduces LV pressure and volume, attenuating myocardial oxygen demand. Evidence regarding the safety and efficacy of TendemHeart remains scarce. When compared to IBAP in CS, percutaneous LVAD provided superior hemodynamic support but did not improve early survival ,47,48. TIn recent propensity-matched registries, VAD use has been associated with higher risks of bleeding, stroke, and death as well as higher cost when compared with the IABP .VA-ECMO  or Extracorporeal life support (ECLS) represents the most advanced and complicated temporary cardiac-pulmonary mechanical support system providing immediate and complete biventricular hemodynamic support with up to 8 L/min of output as well as concomitant gas exchange (oxygenation and carbon dioxide clearance). A centrifugal pump drains deoxygenated blood from the central venous system and returns the oxygenated blood retrogradely into the arterial circulation after interacting with the membrane oxygenator. To mitigate the risk of distal limb ischemia, an 8 Fr distal reperfusion cannula is inserted into the superficial femoral artery, creating an artificial bypass.In a subset of patients with severely depressed contractility and/or concomitant mitral or aortic regurgitation, VA-ECMO may increase afterload and LV end diastolic pressure. In such circumstances, LV unloading with IABP or Impella is mandatory. A recent study showed that among adults receiving VA-ECMO, LV unloading was associated with lower in-hospital mortality despite increased complications including hemolysis and cannulation site bleeding. Compared to VAD, LV unloading with IABP was associated with similar mortality and lower complication rates .Evidence for benefit of VA-ECMO in CS is based on several non-randomized studies reporting survival range from 33.8% to 66.7% in AMI and CS with the use of VA-ECMO ranged ,51.Recent evidence supports favorable outcomes with timely insertion of VA-ECMO. In a large Japanese registry, a shorter time interval between cardiac arrest and VA-ECMO insertion in out-of-hospital resuscitated patients due to cardiac causes was an independent predictor of improved neurologic outcomes at 30 days .Early placement of VA-ECMO in CS may also be beneficial in terms of 30-day all-cause mortality according to a study including CS patients (56% had post-AMI CS). The Shock-to-ECMO time was defined as the time interval between the onset of refractory CS and the time when the ECMO’s centrifugal pump was turned on. A short Shock-to-ECMO time (< 0.9 h) was associated with a 47% lower risk of 30-day mortality when compared to longer Shock-to-ECMO time (>2.2 h) .Data from registries indicate rare use of more than one MCS in a single patient. Among 12,077 patients with CS complicating AMI, 86.5% of patients received one MCS  while 13.5% of patients underwent dual device placement or received another MCS device. The most frequent combinations were IBAP plus Impella (2.3%) and IBAP plus ECMO (1.1%) . In contSelected ongoing MCS studies in CS are summarized in The incidence of mechanical complications and associated CS following AMI has declined in recent years, but mortality rates remain high, between 10 and > 50% . In the Percutaneous transcatheter heart interventions are a viable alternative to surgery in acutely ill patients at extremely high operative risk. Minimally invasive procedures, with or without MCS support, of both mitral and aortic valves have been described in the setting of CS in small case series and registries, with high procedural success rate and improved outcomes ,59,60. HFurthermore, in a small cohort of post-AMI CS cases with acute MR, patients who underwent TEER had similar clinical outcomes compared to patients without CS, provided hemodynamic stabilization was first achieved before MR repair , suggestIn summary, valves intervention in CS patients is an emerging treatment that will probably become more common in the future in selected patients with valve disease and CS.Temporary circulatory support devices are an emerging and rapidly evolving technologies developed as an adjunctive treatment of CS. However, the evidence for survival benefit following their use remains scarce. Multiple platforms are commercially available, each with its own pros and cons. Thus, a high level of expertise is essential to effectively address issues such as device selection, timing of treatment initiation, device troubleshooting, post-implantation care, and weaning. In addition, further prospective randomized data are urgently needed to formulate effective MCS management strategies in order to maximize their potential benefit.


Pentalogy of Cantrell is a rare and deadly syndrome, manifesting as intracardiac anomalies and ventricular diverticulum. Echocardiographers have an insufficient understanding of pentalogy of Cantrell, which may lead to missed diagnoses, especially in cases lacking the most obvious signs.One of twin male infants, at a gestational age of 37 weeks, was found with a cardiac murmur and a pulsatile mass in the midline supraumbilical abdomen for 2 days. Echocardiography on admission indicated congenital heart disease. A cardiac murmur was detected in the 3–4 intercostal space and extensively spread. The infant was diagnosed with pentalogy of Cantrell by ultrasound and computed tomography angiography (CTA) preoperatively. The patient underwent heart deformity surgery and was followed up for 16 months. The patient's cardiac structure and function returned to normal.Intracardiac anomaly and ventricular diverticulum are the primary manifestations of pentalogy of Cantrell. Pentalogy of Cantrell may be diagnosed by combining the ultrasound and CTA findings. Pentalogy of Cantrell is a collection of congenital malformations involving the heart, pericardium, diaphragm, sternum, and ventral abdominal wall and was first reported by Cantrell et al. . The preOne of twin male infants, at a gestational age of 37 weeks, was found with a cardiac murmur and a pulsatile mass in the midline supraumbilical abdomen for 2 days. The patient was admitted to the Affiliated Children's Hospital of Zhengzhou University in November 2016. The mother was para 1, gravida 1. The birth weight was 2.65 kg. There was no family history of genetic disease. A postnatal echocardiogram on day 2 showed cardiomegaly. Due to the possibility of congenital heart disease, the infant was transferred to our hospital. On admission, the heart was enlarged with an uplift of the anterior region. The cardiac sound was strong with a regular rhythm. The heart rate was 125 beats/min. A cardiac murmur was detected in the 3–4 intercostal space and extensively spread. In addition, a pulsatile mass was detected in the midline supraumbilical abdomen. The electrocardiography (ECG) axis was skewed to the left, and the T wave was low and inverted on the I and avL guides. Two atrial septal defects (ASD) measuring 6.8 and 2.0 mm, respectively, from the left to right shunt, a large ventricular septal defect (VSD) measuring 5.7 mm from the left to right shunt, a persistent ductus arteriosus (PDA), and severe tricuspid regurgitation were observed. A left ventricular diverticulum (LVD) herniating into the abdomen through the deficiency of the diaphragm and showing an affluent flow signal was located between the liver and anterior abdominal wall, as detected on color Doppler ultrasound. The diagnoses of LVD, ASD, VSD, PDA, severe tricuspid regurgitation, and pulmonary arterial hypertension were based on the echocardiogram findings . The steThe patient was administered general anesthesia at a low temperature, and heart deformity surgery was performed under extracorporeal circulation. During the operation, the heart was rotated anticlockwise and enlarged. The left ventricle was found in the anterior and left sides. The pericardium defect was found in the apex of the left ventricle. The tubular structure (diverticulum), measuring 10 mm in the midline, extruded from the left ventricle via the pericardium defect. Then, it descended into the abdominal cavity behind the sternum through the diaphragm defect and towards the umbilical region. Partial muscle deficiency was found in the upper anterior abdominal wall. The diverticulum was cut off at the diaphragm, the proximal part of the diverticulum was sutured continuously, and the distal part was ligated. Subsequently, patch closures of ASD, VSD, and PDA ligation were performed. The pericardium and anterior diaphragm defects were also sutured . The ECGThe reported case showed that intracardiac anomaly and ventricular diverticulum are the primary manifestations of pentalogy of Cantrell. Pentalogy of Cantrell may be diagnosed by combining the ultrasound and CTA findings. The results may provide a reference for the recognition and diagnosis of Cantrell's pentad.Cardiac anomaly, intracardiac anomaly, and ventricular diverticulum are the most common and primary manifestations of pentalogy of Cantrell and are correlated with the prognosis , 4. The In conclusion, intracardiac anomaly and ventricular diverticulum are the primary manifestations of pentalogy of Cantrell. The findings of the color Doppler echocardiogram are characteristics for the diagnosis of pentalogy of Cantrell. Therefore, it may be the first-choice modality for the evaluation of pentalogy of Cantrell due to its convenience, easy operation, and high resolution.


Conclusions: Acute ED consumption is associated with a significantly lower cardiac efficiency in healthy minors. The generation of non-invasive LV PVLs might be beneficial in the assessment of subtle changes in LV efficiency. Further studies need to investigate the influence of chronic ED consumption on LV function and morphology.Background: Minors are considered the main consumer group of energy drinks (EDs). The aim of this study was to investigate the acute effects of ED consumption on left ventricular (LV) hemodynamics and efficiency in healthy children and teenagers. Methods: This study was a randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants consumed a weight-adjusted amount of an ED or a placebo on two consecutive days. LV hemodynamics and efficiency parameters were evaluated non-invasively by generating LV pressure–volume loops (PVLs) through simultaneous echocardiography and blood pressure measurement. Results: A total of 24 children and teenagers  were included in the present study. Conventional echocardiographic parameters of LV function did not show significant differences between both beverage groups. The non-invasive generation of LV PVLs revealed a significantly lower cardiac efficiency 240 min after the ED consumption compared to the placebo intake (140.72 (133.21–149.73) mmHg vs. 135.60 (124.78–140.33) mmHg,  Energy drinks (EDs) are sweetened beverages that contain high amounts of caffeine and other stimulants, such as taurine, guarana or glucuronolactone. EDs are particularly popular among children and teenagers, as a survey of the European Food Safety Authority (EFSA) suggests . AccordiSeveral pediatric case reports describe adverse cardiovascular events, such as severe cardiac arrhythmia, arterial hypertension or coronary artery dissection, after acute ED consumption ,3,4. In While minors are considered the main ED consumer group, systemic studies investigating the acute and chronic effects on the pediatric cardiovascular system are lacking. Recently, a publication of our department revealed a significant increase in systolic  and diastolic blood pressure  of up to 5.23 mmHg and 3.29 mmHg after acute ED consumption in healthy children and teenagers, respectively . As an iTo the best of our knowledge, studies evaluating the acute effects of ED consumption on pediatric LV function do not exist. Interestingly, clinical studies with adult subjects revealed a significant increase in LV contractility after acute ED consumption ,10. HoweConventional echocardiographic efficiency parameters of the LV, such as ejection fraction  or global longitudinal strain, are considered load-dependent . To overThe aim of this study was to investigate the acute effects of ED consumption on LV hemodynamics and efficiency in healthy children and teenagers by conducting a randomized, single-blind, placebo-controlled, crossover clinical trial.This study was approved by the Ethics Committee of the Ludwig Maximilians University Munich  on 12 January 2021 (project number 20-0993). Prior written informed consent was obtained from all study participants, and for minor study participants, consent was additionally obtained from parents or legal guardians.For this study, healthy children and teenagers between the ages of 10 and 18 years were recruited prospectively via public calls within the greater Munich (Germany) area. Prior to enrollment, study participants were screened through a personal interview, clinical examination, transthoracic echocardiography, 24 h Holter ECG and 24 h blood pressure measurement. The exclusion criteria were as follows: presence of chronic conditions , history of sudden cardiac death within the family, known allergies against beverage ingredients, regular use of medication with effects on cardiovascular function, regular use of drugs including smoking and alcohol consumption and pregnancy. In addition, study participants were only included if the M-Mode echocardiography-assessed LV EF was ≥55%. The assessment of weight classification, caffeine consumption behavior and ED consumption behavior was described in recent publications of our department ,15.https://www.drks.de/drks_web/, registered on 12 January 2022, identifier: DRKS00027580). Detailed information on the study design, including caffeine abstention, fasting conditions and precise beverage ingredients, are described in recent publications of our department . He. He12]. Blood pressure was measured in supine position with an automated blood pressure device . Precise information on the assessment of blood pressure was given in a recent publication of our department .For the generation of non-invasive LV PVLs, the following parameters assessed via echocardiography and simultaneous blood pressure measurement were required: EDV, ESV, SV, EF, pre-ejection period of the left ventricular outflow tract, total-systolic period of the left ventricular outflow tract, HR, SBP and DBP .Arterial elastance   was calculated as [The end-systolic blood pressure (Plated as (2) Pesm(sb), mmHg/mL)  is the internal energy that is generated by the LV during systole and “stored” in the ventricular wall ,23. Epotlated as ,24(4)V0The stroke work  represents the effective external work conducted by the LV . SW corrThe pressure–volume area  embodies the total LV mechanical energy generated during one single cardiac cycle and was defined as ,18,25(6(sb) was built to describe ventricular–arterial coupling [The ratio of Ea to Eescoupling ,20. Cardcoupling ,26(7)CWThe efficiency of energy transfer between the LV and the arterial system, also named work efficiency , was defined as ,22(8)WECardiac efficiency , describing the amount of PVA required to generate 1 mL of SV, was defined as (9)CE mm(sb), Epot, SW, PVA, Ea/Ees(sb), CW, WE and CE. End points were assessed at baseline as well as at 30, 60, 120 and 240 min after beverage consumption on each study day .The primary end points were EDV, ESV, SV, EF, Ea, Eesp-value < 0.05 was considered statistically significant.As this study was a pediatric pilot study, a prior power analysis was not feasible. Baseline parameters were tested using a paired t-test to determine if the differences between ED and placebo group were normally distributed. The Wilcoxon signed-rank test was chosen if the differences were not normally distributed. To assess the effect of different beverages on the primary end points over time, a two-way repeated-measures ANOVA was performed for normally distributed data (R version 4.1.1). If data were not normally distributed, Ln, Lg or Sqrt data transformation were utilized, and the Wilcoxon signed-rank test was applied. A masked researcher performed data analysis independently. A In total, 27 healthy children and teenagers were recruited. Of those, three subjects were excluded due to insufficient data quality. Participants’ characteristics are demonstrated in For EDV, non-normal distributions were revealed at time 60 within the ED group and at time 240 within the placebo group. Therefore, the original EDV data were transferred into Sqrt form. For ESV, non-normal distributions were shown at time 60 within the ED group and at times 60 and 240 within the placebo group. Hence, the original ESV data were transferred into Ln form. SV data were normally distributed for all time points for each beverage. For EF, non-normal distributions were revealed at times 30 and 120 within the ED group. The original EF data were transferred into Sqrt form.(sb), an extreme outlier was identified. After outlier exclusion, the statistical conclusions remained the same compared to the original data. For Epot, non-normal distributions were revealed at all time points except at time 0 within the ED group. Hence, the original Epot data were transferred into Lg form, resulting in the identification of an extreme outlier. After outlier exclusion, the statistical conclusions remained consistent. The original SW data were transferred into Sqrt form as non-normal distributions were observed at time 240 within both groups. For PVA, non-normal distributions were demonstrated at times 30 and 240 within the ED group and at times 120 and 240 within the placebo group. Hence, the original PVA data were transferred into Sqrt form, resulting in the identification of two extreme outliers. After outlier exclusion, the statistical conclusion remained consistent.Non-normal distributions were revealed for Ea at times 30 and 60 within the ED group and at times 0, 60, 120 and 240 within the placebo group. To achieve normal distribution, the original Ea data were transferred into Lg form. For EesLV hemodynamics did not differ significantly after the ED and the placebo consumption in study participants .(sb), WE and CE, the Wilcoxon signed-rank test was applied for each time point as a normal distribution was not able to be achieved through data transformation. For CW, non-normal distributions were revealed at times 30 and 240 within the ED group and at times 30 and 120 within the placebo group. Therefore, the original CW data were transferred into Lg form. Ea/Ees(sb), CW and WE did not differ significantly after the ED and the placebo consumption in study participants  tended to be higher after the ED consumption but did not reach statistical significance. Interestingly, a recent publication of our department revealed that the acute ED consumption is linked with a significantly lower heart rate in children and teenagers [2 body surface area; caffeine concentration: 30 mg/100 mL) [2 body surface area; caffeine concentration: 30 mg/100 mL) [Caffeine and taurine are considered to increase LV inotropy and hence LV contractility ,27. In teenagers . These feenagers . In conteenagers ,10. Doer/100 mL) . The ED /100 mL) . Interes/100 mL) . Another/100 mL) ,10.The acute vasoactive effects of caffeinated EDs are potentially more profound than their inotropic ones. To maintain SV and EF despite increased LV afterload, more LV mechanical energy might be required after the acute ED consumption, ultimately leading to a significantly lower CE.This study proposes that acute ED consumption is associated with a significantly lower CE. However, the effects of chronic ED consumption on LV function and morphology remain uncertain. Chronic ED consumption might cause unphysiological blood pressure spikes, the onset of arterial hypertension and increased LV afterload, which could ultimately lead to LV hypertrophy. A chronic decrease in CE due to regular ED consumption could result in a higher myocardial oxygen demand, potentially aggravating the process of LV hypertrophy . InteresTo the best of our knowledge, this is the first pediatric study investigating the acute effects of EDs on LV function in healthy children and teenagers. Nonetheless, the present study demonstrates certain limitations, some of which have already been discussed in previous publications of our department ,14,15. T(sb) was only validated in adult subjects; however, high accuracy for pediatric cohorts was demonstrated in the literature [The echocardiographic assessment and the offline analysis of the recorded loops can be considered as user-dependent. For a more reproducible measurement of LV parameters, cardiac magnetic resonance imaging might be superior . As LV fterature . To the Acute ED consumption is associated with a significantly lower LV efficiency in healthy children and teenagers. Moreover, the generation of non-invasive LV PVLs might be beneficial in the assessment of subtle changes in LV hemodynamics and efficiency as no significant differences in LV function were shown through conventional echocardiographic parameters. Further studies need to investigate the influence of chronic ED consumption on LV function and morphology in pediatric as well as in adult subjects. Children and teenagers should be discouraged from drinking EDs, in particular those with pre-existing cardiovascular conditions.