Background: The extracorporeal life support (ECLS) and temporary bilateral ventricular assist device (t-BiVAD) are commonly applied in patients with cardiogenic shock. Prolonged cardiopulmonary resuscitation (CPR) has poor prognosis. Herein, we report our findings on a combined ECLS and t-BiVAD approach to salvage cardiogenic-shock patients with CPR for more than one hour. Methods: Fifty-nine patients with prolonged CPR and rescued by ECLS and subsequent t-BiVAD were retrospectively collected between January 2015 and December 2019. Primary diagnoses included ischemic, dilated cardiomyopathy, acute myocardial infarction, post-cardiotomy syndrome, and fulminant myocarditis. The mean LVEF was 16.9% ± 6.56% before t-BiVAD. The median ECLS-to-VAD interval is 26 h. Results: A total of 26 patients (44%) survived to weaning, including 13 (22%) bridged to recovery, and 13 (22%) bridged to transplantation. Survivors to discharge demonstrated better systemic perfusion and hemodynamics than non-survivors. The CentriMag-related complications included bleeding , thromboembolism , and infection . The risk factors of mortality included Glasgow Coma Scale (Motor + Eye) ≤ 5, and lactate ≥ 8 mmol/L at POD-1, persistent ventricular rhythm or asystole, and total bilirubin ≥ 6 mg/dL at POD-3. Mortality factors included septic shock , central failure , and multiple organ failure . Conclusions: Combined ECLS and t-BiVAD could be a salvage treatment for patients with severe cardiogenic shock, especially for those already having prolonged CPR. This combination can correct organ malperfusion and allow sufficient time to bridge patients to recovery and heart transplantation, especially in Asia, where donation rates are low, as well as intracorporeal VAD or total artificial heart being seldom available. Cardiogenic shock is a low-cardiac-output state, which always leads to systemic end-organ hypoperfusion and acute pulmonary edema in the presence of severe left ventricular dyskinesia. It usually results in life-threatening complications that induce a high mortality rate . PrognosWe retrospectively reviewed our experience of in-hospital cardiac arrest patients, who had witnessed prolonged CPR for more than 60 min without ROSC between January 2015 and December 2019. The data were collected by means of reviewing medical records during hospitalization and follow-up after discharge. This study was approved by our Institutional Review Board of Tri-Service General Hospital, National Defense Medical Center  and all methods were performed in accordance with the relevant guidelines and regulations. Informed consent was waived by the ethics committee based on retrospective review of medical records. According to our treatment strategy of chronic heart failure and ECPR for decompensated cardiogenic shock A–D, CPR 2 with PEEP 8 cmH2O to avoid alveolar collapse. The support pressure was set to 12–15 cmH2O so as to ensure an optimal tidal volume status (6–8 mL/kg), and the plateau pressure was controlled under 24 cmH2O to prevent barotrauma. Extubation was also considered in accordance with the American Thoracic Society guidelines. Systemic heparinization was performed to maintain active clotting time (ACT) around 160–180 s. Routine broad-spectrum prophylactic antibiotic was also used to prevent cannula-related infection, and the end-organ perfusion and function was monitored. Enteral or parenteral nutrition was also started. Once neurologic function was preserved, the CentriMag VAD functioned as a bridge to recovery, heart transplantation, or permanent intracorporeal VAD  was used to assess the conscious level of patients on a daily basis. Due to endotracheal intubation, we only recorded eye opening and motor response without verbal response, which was excluded in GCS scoring. The LVAD flow was kept at 5.0–5.5 lpm with 3300–3500 rpm, while RVAD was kept at 0.5–1.0, lpm lower than LVAD, to prevent the development of pulmonary edema. The mean arterial pressure, central vein pressure, and pulmonary capillary wedge pressure (PCWP) were maintained at 75–90 mmHg, 12–15 mmHg and 12–15 mmHg, respectively. The oxygenator could be easily disassembled in the ICU as long as pulmonary edema was resolved. Usually, we kept inotropes at 5 mcg/kg/min to maintain LV outflow and prevent blood stasis and subsequent thrombus formation over LV and aortic root. During the VAD period, the ventilator was set at 40% FiOreal VAD A. In casWeaning of CentriMag VAD was only considered in cases where the inotropes were tapered and systemic perfusion was adequate. ACT was adjusted up to more than 200 s via systemic heparinization before lowering the CentriMag revolution. For RVAD, weaning was always initiated prior to LVAD. RVAD weaning was discontinued in cases where signs of RV overload, such as RV distension and left deviation of septum by echocardiography, and frequent suction event concomitant with decreased flow of LVAD, were noted. Once RVAD weaning was successful, LVAD weaning was then initiated. For LVAD, weaning was considered in cases of the LVEF > 40%. The flow was reduced gradually to 1.5 L/min with a rate of 200 mL per day. LVAD weaning was discontinued if signs of LV overload, such as pulmonary edema by chest film, LV distension by echocardiography, and high PCWP by Swan-Ganz catheter , were noted. Withdrawal and removal of Bi-VAD occurred when both RVAD and LVAD were weaned off. Otherwise, patients were referred for transplantation or durable intracorporeal VAD.p-value less than 0.05 was considered statistically significant. Continuous variables were expressed as means ± standard deviation and were compared using the unpaired t-tests. Continuous variables with non-Gaussian distribution were expressed with medians and interquartile range. Categorical variables were expressed as percentages and were compared with the χ2 test or Fisher’s exact test. Regarding hemodynamic improvement and end-organ perfusion, both POD-1 and POD-3 were compared to the pre-VAD baseline overall, and in survivors and non-survivors, respectively. A univariate analysis using multinomial logistic regression was employed to analyze the risk factors of mortality. Survival was calculated using the Kaplan–Meier method.SPSS 25.0 statistical software  was used for all analyses, and a 2. After t-BiVAD implementation, 10 patients were detected with pulsatile (pulse pressure), 33 had PEA/Asystole, and 16 had sustained VT/Vf. The mean LVEF was 11.3 ± 5.77%. The median VAD duration was 343 h (interquartile range 1004 h).A total of 59 consecutive patients with various etiologies of cardiogenic shock were enrolled between January 2015 and December 2019 A. Table 2) was significantly improved in both groups. The CentriMag-related major complications and causes of mortality are presented in n = 22), systemic embolization (n = 5), infection (n = 4), and acute kidney injury (n = 41) ((n = 41) . There w(n = 41) . Thirtee(n = 41) B,C, and (n = 41) D. The 2-(n = 41) E.n = 53), which would help ischemic organs to obtain optimal oxygenation but also compensate the oxygen debt during CPR as soon as possible. Of course, with the RV function preserved, isolated LVAD is adequate for LV dysfunction only  has a mag-levitated impeller design that has been reported to minimize friction and destruction of blood cells, preventing hemolysis and thrombus formation. A maximal blood flow of up to 9.9 L/min provides sufficient cardiac output to almost all Asian body sizes . In Taiwion only C. For biion only D. This cTakeda et al. reported on a minimally invasive ventricular assist system with oxygenator that could spare the sternum, minimize bleeding, avoid severe adhesion, and convenience the subsequent durable VAD implantation or transplantation ,12. We hFirst, this was a single-center study. The etiology of cardiogenic shock is too versatile and it is limited in performing intragroup and intergroup comparisons. Further, the results are based on our clinical practice policy, which may not be applicable to other heart centers. Second, the retrospective analysis utilized a historical chart review, and many unmeasured confounders might cause residual bias. However, it is difficult to design prospective randomized-controlled studies in this critical scenario. Third, a relatively small sample size and short-term follow-up may have also affected the validity of our findings. More cases and a longer-term follow-up period should be employed.In light of the extremely poor prognosis of patients with prolonged CPR, combined ECLS and t-BiVAD could be a safe and effective treatment to rescue patients with cardiogenic shock and sequelae end-organ malperfusion. In our cohort, survival to weaning-off, to discharge, and 1-year survival were 44.0%, 42.3%, and 40.6%, respectively. We, furthermore, demonstrated versatile configurations and extended running, which allows for a sufficient time to bridge patients to recovery and heart transplantation.


We present an interesting case of an 88-year-old man who was referred to our arrhythmia service for an upgrade of his dual-chamber pacemaker to a biventricular pacemaker for right ventricular pacing–induced cardiomyopathy. The patient was found to have stenosis of the left subclavian vein. Here, we describe the approach used to perform venoplasty in this patient. After venoplasty of the left subclavian vein, the patient did not have suitable coronary venous anatomy for deployment of the coronary sinus lead. Subsequently, a His lead was implanted. We achieved significant narrowing of the QRS with good thresholds and other lead parameters. Through this case report, we seek to present our approach of venoplasty in patients with occluded venous access for either an upgrade or a de novo implant. The options included implanting a new system from the right side, except that the patient had a chemotherapy port on that side, or a surgical left ventricular (LV) lead implantation. Ultimately, we decided to perform a balloon venoplasty of the left subclavian vein stenosis. A left antecubital vein access was upsized to a 6-French Terumo slender sheath . A repeat venogram demonstrated the occlusion of the left subclavian vein and collaterals from the left cephalic as well as the basilic vein into the left internal jugular vein. At the site of previous leads, there was no flow noted . A 0.035-in angled Navicross catheter was advanced over an angled glidewire advantage, which, by gentle manipulation, was successful in crossing the total occlusion . The tip of the catheter was then placed in the inferior vena cava, and the angled glidewire advantage was exchanged with a Wholey wire. An 8.0- × 6-mm balloon was advanced; however, the balloon failed to cross the obstruction. The Wholey wire was exchanged with a 0.014 balance middleweight 300-cm wire. A 4.0- × 80-mm ultraverse balloon  was used for balloon angioplasty, which was upsized to an 8.0- × 60-mm balloon. Balloon angioplasty was performed with an 8.0-mm balloon at 6 atm . Repeat cineangiography revealed adequate flow across the previously blocked subclavian vein without any dissection or perforation.An 88-year-old man with a history of complete heart block status after dual-chamber pacemaker implantation was sent to our arrhythmia clinic for the management of right ventricular (RV) pacing–induced cardiomyopathy. He had a history of paroxysmal atrial fibrillation and chronic kidney disease (CKD) with a creatinine level of 1.5 mg/dL. He was also suffering from chronic lymphocytic leukemia and had a chemotherapy port in the right subclavian vein. The patient was experiencing heart failure (HF) symptoms, including shortness of breath and leg swelling. His echocardiogram showed an ejection fraction (EF) of 40%. A stress test was performed, which did not reveal any ischemia. Given his need for RV pacing and cardiomyopathy, an upgrade of his dual-chamber pacemaker to a biventricular (BiV) pacemaker was offered. The patient was brought to the electrophysiology lab in the post-absorptive state. Routine venography of the left subclavian venous system was performed, which revealed subclavian vein stenosis . Multiple attempts at placing the CS lead over the angioplasty guidewire failed. A renal vein subselector was used; however, we could not cannulate the side branch with a guidewire. The options were to perform an angioplasty of the CS lead or conduction system pacing (CSP) either with His-bundle pacing (HBP) or left bundle pacing. Given his history of CKD and earlier subclavian venoplasty (SV), it was decided to limit further use of the contrast and instead perform HBP. A Medtronic SelectSecure 3830 lead  was advanced over the C315 delivery system. Pace-mapping was performed in the area where we had a good His signal. Selective and non-selective capture of the His bundle was demonstrated. The helix was delivered by clockwise rotation of the lead . The pacing threshold was 1.2 V at 0.4 ms. An electrocardiogram showed a significant narrowing compared to baseline  and 5B.Subsequently, the pocket was opened, and the device and the leads were dissected out. Using a micropuncture needle set, subclavian vein access was obtained. A Worley delivery sheath was advanced over the guidewire. CS cannulation was performed without any difficulty. A CS venogram was recorded, which revealed a tortuous lateral branch that tapered abruptly The patient was subsequently discharged home after an overnight observation. He was followed up in the clinic at 6 weeks and was feeling much better with improvements in his symptoms of fluid retention and shortness of breath. His EF on follow-up was noted to be 50%.This case illustrates the anatomical barriers that can be encountered during a device upgrade of a patient with multiple comorbidities and the tools and techniques available to an implanting physician in the current era to overcome and troubleshoot these problems. The decision to upgrade the pacemaker to a BiV pacemaker was made in view of the symptomatic HF with LV dysfunction, a high percentage of RV pacing, and the absence of inducible ischemia.2 Previous use of transvenous temporary leads, LVEF < 40%, and advanced age (>65 years) were found to be independent risk factors for a higher incidence of venous occlusion. Most of the patients in these studies were asymptomatic due to the collateral venous circulation that developed as the stenosis progressed.The first anatomical obstacle in our case was the subclavian occlusion precluding access to implant an LV lead. The incidence of subclavian vein stenosis after device implantation varies widely in the literature, ranging from 30%–50%.3 The 2017 Heart Rhythm Society expert consensus statement includes SV as an option when venous access becomes an issue due to occlusion of the desired access point.5 Once the access was established in our case with SV, another anatomical challenge emerged in an attempt to implant an LV lead.In our situation, one of the options was to implant a cardiac resynchronization therapy (CRT) pacemaker device from the other side. However, the patient had a chemotherapy port on the right side, making that route of access unavailable. Crossing intraluminal occlusions followed by SV has been demonstrated to be a safe alternative. The largest series reporting the use of SV for lead implantation included 373 cases documented over an 11-year period. Successful access was achieved in 371 of 373 cases with no adverse clinical outcomes, including distal embolization, venous disruption, and damage to the leads.7 However, CRT is not without its limitations. One major limitation of BiV pacing in CRT is the failure of LV lead deployment due to limitations in CS anatomy,8 and the standard of care suggests epicardial LV lead insertion as the next alternative. Historically, in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT), 7.5% of patients (n = 82) who were assigned to the CRT-implantable cardioverter-defibrillator (ICD) group received an ICD-only device during the trial because of technical difficulties in positioning the LV pacing lead in the coronary vein.9 Overall, an unfavorable CS anatomy precludes the delivery of an LV lead placement in 5%–8% of patients, and the lead position is suboptimal in another 15%–20% of patients.10 In a contemporary meta-analysis of 29,503 patients, the overall rate of failure of implantation of an LV lead was 3.6% . The rate of failure in studies that commenced before 2005 was 5.4% , and that in studies performed from 2005 onward was 2.4% . The causes of failure (reported for 39% of failures) also changed over time. Failure to cannulate and navigate the CS decreased from 53% to 30% (P = .01), and the absence of any suitable, acceptable vein increased from 39% to 64% (P = .007).8 Our case was representative of this trend, with no suitable branch for LV lead placement found after CS cannulation. Therefore, we had to seek alternatives to an LV lead in our case.We know that CRT is the only known non-pharmacologic HF therapy that improves cardiac function, functional capacity, and survival while decreasing cardiac workload and hospitalization rates in chronic systolic HF and conduction system disease.7 The 2021 European Society of Cardiology guidelines11 recommend HBP as a treatment option together with other techniques such as surgical epicardial lead (class IIa level of evidence B indication) in CRT candidates in whom CS lead implantation is unsuccessful.Presently, CSP serves as an attractive bailout strategy in patients with a lack of coronary venous access, diaphragmatic pacing, and/or failure to respond to classic CRT.12 and is steadily gaining interest for providing a more physiological alternative to RV pacing. It may also correct intraventricular conduction delay in a subset of patients, thereby providing an alternative to BiV pacing for treating HF. There is growing evidence, mainly from observational studies, that HBP may be safe and effective in these settings, although large randomized controlled trials (RCTs) and long-term follow-up data are still lacking.13 Lustgarten et al. were the first to design a prospective crossover study in which patients received both HBP and traditional CS LV leads. They found comparable results at 1 year of follow-up between functional outcomes  and echocardiographic outcomes . The study was an important proof of concept for HBP-CRT as a potential first-line strategy for CRT.14 In another study, Vijayaraman et al. showed successful HBP in 90.6% of patients (n = 32), 14 of whom had failed CS leads and 2 who were non-responders to BiV-CRT. They observed QRS narrowing and improvements in LVEF and NYHA functional class, reiterating that HBP in lieu of an LV lead is also feasible.15 Ajijola et al. evaluated 21 patients with an indication for CRT implant to incorporate a His-bundle lead for CRT in lieu of a CS lead. HBP implantation was successful in 76% of patients (16/21 patients) with significant narrowing of the QRS duration and improvement in NYHA class, LVEF, and LV internal dimensions in diastole at 6 months of follow-up.16 Sharma et al. assessed 106 patients with CRT indications for HBP as a rescue strategy for failed LV lead or non-response to BiV pacing, or as a primary strategy for atrioventricular (AV) block, bundle branch block, or high ventricular pacing burden as an alternative to BiV pacing. The study reported a 90% success rate with significant QRS narrowing, an increase in LVEF, and an improvement in NYHA class after a mean follow-up of 14 months.17HBP was first reported in humans in 200018 In this first randomized pilot trial, His-CRT did not demonstrate significant improvements in electrocardiographic or echocardiographic parameters compared to BiV-CRT. This study was underpowered to detect differences of <10% between groups, and the existence of a type II error cannot be excluded. Importantly, an intention-to-treat analysis in the presence of high crossover rates cannot directly assess treatment efficacy.The first prospective RCT to compare corrective HBP versus BiV pacing for CRT was the His Bundle Pacing vs. Coronary Sinus Pacing for Cardiac Resynchronization Therapy (His-SYNC) pilot trial, which was an investigator-initiated study conducted at 7 centers in the United States.Challenges with HBP include the complexity of implant and significant learning curve, higher acute pacing thresholds with a rise in follow-up, and diminutive R-wave sensing. What is sorely needed is both refinement in delivery tools of His leads and more data on clinical outcomes after HBP in patients with HF. The His Optimised Pacing Evaluated for Heart Failure Trial (HOPE-HF) (NCT02671903) will provide some data in this regard, as it evaluates the use of HBP in HF patients with long AV delay.We were able to achieve an acceptable threshold for the His lead and QRS narrowing, which is a surrogate for electrical resynchronization. The patient was seen for follow-up at 6 weeks and 3 months. He reported an improvement in his symptoms, and an echocardiogram revealed an EF of 50% at 3 months.The cardiac device–implanting physician has multiple tools and techniques available in their armamentarium to overcome some of the anatomical challenges during device implants, especially during device upgrades. One must be familiar with these contemporary tools and techniques in order to deliver the best results to the patient in terms of procedural success as well as long-term clinical outcomes.


Improvement of left ventricular ejection fraction (LVEF) in patients after the first manifestation of heart failure with reduced ejection fraction (HFrEF) has currently been observed more frequently than it was years ago. This appears to be due to the early initiation of comprehensive HF therapy. According to these observations, a new HF syndrome category, heart failure with improved ejection fraction (HFimpEF), was introduced. In this short review, we present definitions of reverse remodelling, myocardial remission, and myocardial recovery. We provide an overview of clinical research aimed at evaluating reverse remodelling in different populations of patients with HFrEF. Clinical and imaging characteristics and biomarkers identified as predictors of reverse remodelling and improvement of the LVEF are discussed. We also briefly address the current views on the management of patients with HFimpEF. In-depth study and knowledge of the molecular mechanisms underlying the reverse remodelling process may lead to the identification of new individualized therapeutic approaches for HFrEF. Myocardial injury, haemodynamic overload, and excessive neurohumoral activation are the main triggers of several pathophysiological processes leading to structural and functional changes in the myocardium, which are referred to as cardiac remodelling. This pathological process is responsible for the onset and progression of heart failure. Pathological remodelling causes hypertrophy, dilatation, and spherical left ventricular (LV) remodelling, as well as contractility disorders, and typically leads to heart failure with reduced ejection fraction (HFrEF). In the past, systolic dysfunction and remodelling were considered to be irreversible processes and were associated with an unfavourable prognosis. Currently, it is known that favourable changes in LV geometry and LV systolic function improvement can be observed in a significant percentage of patients with HFrEF. These morphological and functional myocardial changes are referred to as reverse remodelling (RR). RR is basically accompanied by termination or reversal of the pathophysiological processes responsible for the initial pathological remodelling. From a morphological point of view, the LV dimensions start returning to normal; mitral regurgitation becomes less severe, and the contractility and LV ejection fraction (LVEF) show improvement. In clinical practice, RR is associated with improved functional capacity and reduced hospitalization and mortality rates. According to these characteristics, the induction of RR becomes a major therapeutic target in patients with HFrEF. The predictive factors of RR have been partially described, but detailed knowledge of them, as well as accurate RR prediction, is important for a therapeutic strategy decision, especially when expensive device therapy is being considered.documented reduced LVEF <40%,an increase in LVEF of at least 10% from the baseline value,an increase in LVEF to >40%.In recent years, there has been an increase in the number of studies focused on the group of patients with RR. This phenotype of heart failure is referred to as heart failure with improved ejection fraction (HFimpEF) or heart failure with recovered ejection fraction. Echocardiography plays a dominant role in the evaluation of RR. The presence or absence of RR is identified by the difference between the initial and follow-up values of the measured parameters Fig. . The timTable cardiac remission. Cardiac remission may or may not be associated with improvement in LVEF, and therefore, it is clinically stabilized regardless of functional myocardial changes. If cardiac remission is associated with improvement in systolic function as well, we refer to this condition as myocardial remission. The term remission refers to a transient condition because despite the improved function, the cellular, molecular, and genetic processes are not in their physiological state, and these patients are still in danger of systolic dysfunction progression. In rare cases, complete normalization of pathological processes, including gene expression, may occur, which is typically accompanied by normalization of systolic function as well, which in practice means a cured patient. We also describe so-called myocardial recovery in these patients, but today, it is practically impossible to distinguish this stage from myocardial remission. Patients with myocardial remission represent the dominant portion of HFimpEF patients, as shown by several studies focused on this phenotype of patients. These studies confirm the persistence of abnormal gene expression as well as abnormal global longitudinal strain (GLS) of the left ventricle. After RR and improvement in LV systolic function due to LV assist device implantation, only approximately 5% of genes that are dysregulated in HF return to normal, despite morphological and functional heart recovery.In the heart failure trajectory, we can observe various changes in clinical condition and LV systolic function. The stage of long-term disease stabilization, when patients are monitored on an outpatient basis, tolerate treatment well, and do not require hospitalization for decompensated heart failure, is referred to as The aetiology of heart failure is an important determinant of RR induction. In general, patients with an ischaemic cause of HFrEF are less likely to achieve RR than patients without ischaemic myocardial damage. Due to almost no ability of cardiomyocytes to regenerate, their postinfarction loss is practically irreversible, and if ventricular dysfunction is already present, no functional improvement is expected in the future. In contrast, due to the increased demands on the intact working myocardium, progression of the dysfunction is more likely to occur.DCMP dominates among the nonischaemic causes of HFrEF, with nonfamilial forms of DCMP having a more favourable prognosis and a higher probability of RR induction. DCMP associated with truncating titin mutations usually responds well to drug treatment, and RR is more likely to develop than DCMP associated with laminin A/C and other sarcomere protein gene mutations. The estimated probability of RR induction due to proper treatment in patients with idiopathic DCMP is approximately 40% .A relatively high rate of RR induction is also expected in patients with mild forms of myocarditis  , periparWhen using echocardiography in RR prediction, it is also necessary to evaluate, in addition to basic morphological and functional parameters, the deformation characteristics of the myocardium using speckle-tracking echocardiography as it reflects contractility and LV systolic function more reliably and seems to predict RR better. Some of the standard echocardiographic parameters are considered to be predictors of RR, including mild/moderate mitral regurgitation, higher TAPSE, smaller left atrial volume, and smaller LV end-diastolic volume. A larger end-diastolic dimension of LV and lower LVEF are paradoxical RR predictors, but these patients actually have a worse prognosis. However, an initially larger and more dysfunctional ventricle can more easily achieve an increase in LVEF even with a smaller change in LV geometry, but LVEF is unlikely to reach 40%; therefore, we should not consider these parameters as RR predictors. LV GLS assessment represents a more sensitive method for systolic function assessment that is relatively independent of ventricular volumes. Several studies have confirmed that GLS is a reliable RR predictor . In a stIn addition to echocardiography, magnetic resonance imaging of the heart also plays an important role in RR prediction. Late gadolinium enhancement (LGE) represents the main parameter predicting RR. Patients with a low degree of LGE or no LGE at all are more likely to achieve RR , 26.Today, the medical and device treatments used to improve the prognosis of HF patients also have a well-documented effect on reverse LV remodelling. Due to their long-term use, beta blockers and preparations that interfere with the renin-angiotensin aldosterone system  have well-described mechanisms affecting RR. Newer drugs, including ARNI and SGLT2i, also have a demonstrated effect on RR, but no detailed explanation of their mechanism of action has been fully understood yet. Table Biomarkers are used routinely for heart failure diagnosis, prognosis assessment, and response to treatment monitoring. Currently, it is possible to evaluate the degree and severity of some pathophysiological processes accompanying the onset and progression of heart failure by using biomarkers . The ideThe contribution of NT-proBNP in RR prediction has been demonstrated in several studies that evaluated its dynamic changes. A significant NT-proBNP decrease was associated with LVEF improvement. In the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) study, which included 269 patients, a decrease in NT-proBNP levels below 1,000 ng/L at a time interval of 12 months after treatment initiation was correlated with LVEF improvement and LV volume reduction. No unambiguous correlation between the NT-proBNP initial value and RR prediction has been demonstrated in several larger studies.Troponin T as a myocardial damage marker appears to be a promising RR predictor. A study on a heterogeneous group of HFrEF patients showed a higher incidence of RR in patients with an initial highly sensitive troponin T value <11 ng/L than in patients with higher troponin T levels .Suppression of tumorigenicity 2 (ST2) is a marker of pathological remodelling that reflects the degree of fibrosis and LV hypertrophy in patients with HFrEF. Higher soluble ST2 levels have been associated with poorer prognosis of patients with HF in several studies , 30, 31.After the definition of a new group of patients with heart failure, new questions regarding their management have arisen. Due to the incomplete understanding of various mechanisms of RR and a lack of large randomized clinical trials, no official guidelines for the management of patients with HFimpEF have yet been published, and only the consensus of experts is being followed.n = 25) and a treatment-continued group (n = 26), with an assignment ratio of 1:1. DCMP relapse  was considered the primary outcome. Within 6 months, 11 patients (44%) achieved the primary outcome in the discontinued-treatment group, while no patient achieved the primary outcome in the continued-treatment group. Subsequently, in the next 6 months, 25 patients from the continued-treatment group terminated their treatment, and 9 (36%) of them achieved a primary outcome within 6 months [A TRED-HF study addressed the issue of treatment termination or treatment continuation in patients with HFimpEF after LVEF and LV volume normalization and NT-proBNP decrease to less than 250 ng/L . In that6 months .Repeated progression of the disease after previous recovery was examined in a study involving 85 patients with DCMP who continued with their heart failure therapy. Progression of systolic dysfunction after 50 ± 33 months was observed in 38% of cases and was associated with older age, greater LVEDD, and the presence of diabetes mellitus . DiscontPatients with HFimpEF should be monitored regularly on an outpatient basis for the risk of repeated progression of systolic dysfunction. The frequency of check-ups should be every 6 months during the first 3 years. The regular outpatient check-up should include clinical examination focused on signs of congestion, physical capacity evaluation, electrocardiogram, NT-proBNP level measurement, and echocardiography. In patients with cardiomyopathy with a higher risk of atrial arrhythmias, an ECG Holter of at least once every 2 years is recommended. The indication for primary prevention of sudden cardiac death in patients with HFimpEF is ambiguous, but ICD implantation should be considered in patients with an identified genetic cause of cardiomyopathy at high risk of ventricular arrhythmias .It is already known that some patients diagnosed with HFpEF are actually patients who have already had a reduced ejection fraction, which has improved due to certain factors . They foStudies evaluating the clinical outcomes of patients with HFimpEF have consistently shown a reduction in mortality and hospitalization rate and a better quality of life compared to patients with HFrEF, heart failure with mild reduced ejection fraction, and HFpEF , 42, 43.In conclusion, early identification of heart failure, accurate aetiological diagnosis (including genetic testing), and proper treatment with adequate dose titration are key factors for predicting and achieving RR in patients with HFrEF. In-depth study and knowledge of the molecular mechanisms involved in RR may lead to the identification of new individualized therapeutic approaches for HFrEF.Dr. Eva Goncalvesova declares the following disclosures : Servier, AOP Orphan Pharmaceuticals, Boehringer-Ingelheim, Johnson & Johnson, Merck, Novartis, Amgen, Pfizer. Dr. Martin Chudy has no conflicts of interest to declare.The manuscript was supported by a grant from the Slovak Society of Cardiology.Martin Chudý and Eva Goncalvesová were involved in conception, design, literature review, and critical revision of the manuscript and completed, read, and approved the final manuscript.


The aim of the study was to evaluate the efficacy and safety of stenting for branch pulmonary artery stenosis using a biodegradable nitride iron stent  were included in this pre and post-intervention, prospective, cohort and preclinical study. All cases underwent transthoracic echocardiographic (TTE), chest radiography, along with computed tomography  and right heart catheterization. Different types of biodegradable nitride iron stents were implanted. TTE was performed serially 1 day, 1 month and 3 months after the procedure to evaluate the rate of restenosis and right ventricular function.p = 0.008) and left ventricular ejection fraction (p < 0.01). The early trans-tricuspid inflow velocities E/E′  correlated significantly with E′/A′ (p = 0.009). FAC and E′/A′ were statistically different from those prior to stenting (p = 0.041 and p = 0.035) when tested one month postoperatively. At three months postoperatively, only E/A showed a statistical difference (p = 0.015).Stenting was successful in 11 patients. There were no major adverse cardiovascular events related to the device or to the procedure. Blood perfusion in the branch pulmonary artery was improved immediately. At follow-up, there was no significant restenosis that required re-intervention. None of the patients suffered from in-stent thrombosis, vascular embolism, stent displacement or heart failure. Compared with normal values, there were statistical with regards to FAC, E/A and E′/A′. Furthermore, we found that TAPSE correlated significantly with pulsed Doppler S wave ; NCT04973540). Pulmonary artery stenosis (PS) is often associated with congenital heart disease (CHD) and a wide range of genetic syndromes, thus leading to elevated right ventricular or main pulmonary artery pressure, arrhythmia, imbalanced lung perfusion, systemic cyanosis, and sudden death –3. At prvia the femoral vein or artery that allow unrestricted vascular growth    and righThe inclusion criteria were as follows: (1) patients must between 1 and 14 years old; (2) patients needed to have congenital or secondary pulmonary artery stenosis , and meet one of the following criteria: (A) the pressure gradient across the stenosis was ≥ 20 mmHg as measured by a catheter; (B) the degree of pulmonary artery stenosis was ≥ 50% /; (C) the ratio of right ventricular systolic pressure to aortic systolic pressure was ≥ 50%; (3) patients and their families were compliant with the requirements of the study, and were willing to participate voluntarily, sign the informed consent form, complete the 2-year follow-up; and (4) patients had a life expectancy of > 2 years after successful stent implantation.The exclusion criteria were as follows: (1) patients who had a history of disease related to iron overload or iron disorder, such as hereditary hemochromatosis; (2) patients with cardiopulmonary function that could not tolerate surgery, such as those with severe heart failure (NYHA Grade III and above) that could not be controlled by active medical treatment; (3) patients with known allergies to contrast agent, iron and its degradation products; (4) patients with hemorrhagic disorders; (5) patients with contraindications to antiplatelet agents and anticoagulant therapy; (6) patients with thrombosis at the vascular wall of the target lesion or the distal or proximal location; (7) patients with confirmed severe renal or hepatic insufficiency who were unsuitable for the index procedure according to the investigator’s judgment; (8) previous stent implantation had been performed to treat the target lesion; (9) patients with severe stenosis or excessive tortuosity in the targeted vessels, or anatomical abnormalities, thus making it difficult for the device to reach the target lesion; (10) patients with other conditions that are not suitable for stent delivery or balloon expansion; (11) patients who have already participated in another drug or medical device clinical trial that have not yet completed or withdrawn within 3 months before the screening period of the current trial; and (12) patients who were not suitable for participating in the trial as per the investigator’s judgment.® Angel™  have different sizes. The diameters of the stents range from 2.25 to 10 mm. The lengths of the stents range from 8 to 38 mm. The sizes of the delivery long sheath range from 4 to 9F. The radial support of the stent ranges from 90 to 140 kpa. All patients underwent right heart catheterization under general anesthesia. A TERUMO 6F (Japan) femoral sheath was used to puncture the right or left femoral vein. The intravenous dose was 100 U/kg of heparan. The right ventricle, pulmonary artery trunk, and the distal branch of the pulmonary artery pressure were measured with a TERUMO 6F-MPA2-100 (Japan) catheter along the right femoral vein, the right atrium, the right ventricle, the pulmonary artery trunk, the branch pulmonary artery. Then, we calculated the pressure gradient across the stenosis. Right ventricle or main pulmonary artery (mPA) angiography was performed in anteroposterior, lateral and cephalic positions at 15°–20° to assess the morphology of stenosis in the branch pulmonary artery; for this, we used a TERUMO 5F-pigtail (Japan) catheter. Care was taken to note the position of the branching vessels and their relationship to the stenosis. Following pulmonary artery angiography, different size stents were mounted on balloons and directed to straddle the lesions with an 6F or 8F long sheath guide (Cook Inc) over a 0.035-inch extra-stiff exchange interventional wire . Following placement, we attempted to dilate both the proximal and distal pulmonary vessels. After catheterization, low molecular weight heparin sodium was injected subcutaneously twice at 100 U/kg–1 after 4 and 16 h after intervention. Acetylsalicylic acid (3 to 5 mg/kg–1/d–1) was prescribed for 6 months, and clopidogrel (1 mg/kg–1/d–1) was prescribed for 1 month.The biodegradable nitride iron stent IBSPrior to stent implantation, patients underwent routine transthoracic echocardiographic (TTE), chest radiography and computed tomography (CT) with a 256-slice scanner equipped with a multiple detector . Blood was also drawn so that we could determine the levels of iron metabolism indicators. TTE examination was carried out preoperatively using IE33, IE Epic-7C  and Vivid E 9  ultrasound systems with a transducer of 5–8 MHz. The follow-up period was 2 years. Following implantation, we determined pulmonary artery perfusion (the diameters of the stents and the pressure gradients across the stents) and right ventricular function parameters  with TTE on day 1, month 1,3,6,12,24. The morphology and degradation of the stent were evaluated by MDCT one year after implantation. When suspected stent stenosis was confirmed by echocardiography within 1,3,6 months after implantation, MDCT examination was performed, and angiography was necessary. Iron metabolism, liver and kidney function and coagulation indexes were examined half a year after operation. The Pre- and post-operative TTE images and MDCT images were reviewed by two independent experienced pediatric cardiologists to determine the location and morphology of the stenosis in the branch pulmonary artery.The primary end point was composite, combining major adverse cardiovascular events that included cardiovascular mortality, in-stent thrombosis, vascular embolism, stent displacement, and heart failure. Secondary endpoints were branch pulmonary artery diameter evolution, complications related to the procedure, intervention rate, and all-cause mortality.t-test or the Mann-Whitney U test as appropriate. All analyses were performed using SPSS Statistics 23  and a two-sided P < 0.05 was considered as statistical significance.Continuous variables are expressed as mean standard ± deviation or median with range. Categorical variables are presented as numbers and proportions, and between-group differences were analyzed using the Student’s A total of 11 children with PS were included in the current analysis. There were two female patients and nine male patients. Ages ranged from 36 to 86 months (mean age: 59.7 ± 16.05 months). Weight ranged from 14 to 20 kg (mean weight: 16.8 ± 1.94 kg). All of the children with PS had congenital heart diseases; the most commonly detected abnormalities were tetralogy of Fallot (TOF) and pulmonary atresia with ventricular septal defect (PA/VSD), both of which were found in four (36.4%) patients, followed by VSD combined PS in two (18.2%), and complete transposition of the great artery (TGA) in one (9%) patient . All patBlood samples were taken from each child to determine the levels of indicators for iron metabolism. The mean serum level of iron was 13.6 ± 5.5 μmol/L; the mean serum levels of transferrin and ferritin were 2.5 ± 0.35 g/L and 66.2 ± 58.9 ng/ml, respectively. Preoperative indices of iron metabolism indices were normal. Since the other patients did not reach the 6-month follow-up period, indices of iron metabolism were measured again in only 3 patients at 6-month follow-up; no significant abnormalities were found.Transthoracic echocardiographic (TTE) and MDCT was carried out preoperatively in 11 cases. The parameters measured in MDCT included: A1 (narrowest diameter), A2 , A3  and L (the length of the lesion). The narrowest diameters of the lesion vessels ranged from 0.86 to 4.714 mm (mean diameter: 2.95 ± 0.998 mm), the proximal diameters ranged from 0.86 to 10.06 mm (mean diameter: 4.35 ± 2.52 mm), the distal diameters ranged from 3.77 to 10.31 mm (mean diameter: 7.37 ± 1.95mm), and the length of the lesion ranged from 9.16 to 23.73 mm (mean length: 15.15 ± 5.32 mm) . AccordiEleven cases underwent right heart catheterization under general anesthesia. The measured parameters included: A1 (narrowest diameter), L (length of the lesion vessels) and A2 . The hemodynamic parameters included: preoperative/postoperative right ventricle (RV) pressure, main pulmonary artery (mPA) pressure, and pressure gradient . Nine pap < 0.05). Preoperative mean pressure gradient across the stenosis was 44.5 ± 22.1 mmHg; this decreased to 14.7 ± 8.9 mmHg after stenting. Preoperative mean RV systolic pressure and mPA systolic pressure were 73.36 ± 17.10 mmHg and 63.80 ± 21.04 mmHg, respectively; these decreased to 45.50 ± 12.62 mmHg and 46.40 ± 10.26 mmHg, respectively, after intervention and were both statistically significant .With regards to the primary end point, stenting was successful in 11 patients. There were no major adverse cardiovascular events related to the device or to the procedure. With regards to secondary end points, as the narrow pulmonary artery was expanded, the blood perfusion in the branch pulmonary artery improved immediately. The narrowest mean diameter of the lesion vessels was 3.37 ± 1.2 mm before stenting; these were dilated to 7.92 ± 1.62 mm after stenting. There was a significant difference in the immediate postoperative stenting effect in terms of the diameter of the lesion vessels and the pressure gradient across the stenosis  and the pressure gradients across the target vessels were significantly reduced after one day and three months when compared with that before stenting (p = 0.021 and 0.037). Furthermore, there was no significant difference in the vascular diameters and pressure differences between groups when tested 1 day, 1 month and three months after stenting (p = 0.642 and 0.445), thus indicating that no significant restenosis was detected during follow-up that required re-intervention. None of the patients experienced in-stent thrombosis, vascular embolism, stent displacement, or heart failure.Eleven cases underwent TTE examination preoperatively and at follow-up intervals. The narrowest mean diameter of the lesion vessels was 4.58 ± 1.92 mm before stenting and the mean pressures gradient across the stenosis was 48.5 ± 26.9 mmHg. After 1 day, 1 month, and 3 months, we evaluated the diameters of the lesion vessels and the pressure gradients across the stents , 5. The p < 0.01) (p = 0.041 and p = 0.035). Three months post-stenting, only E/A showed a statistical difference (P = 0.015)  . These r= 0.015) .r = 0.393; p = 0.008) and LVEF , E/E′ correlated significantly with E′/A′ , RA volume correlated significantly with RVD1 and RVD2 volume , and RVD1 volume correlated significantly with RVD2 volume   .Primary or secondary branch pulmonary artery stenosis complicates the management of congenital heart diseases. Tetralogy of Fallot and pulmonary atresia with ventricular septal defect are the most common congenital heart diseases involved. This is consistent with our own clinical trials results. Over the past several decades, technological advances and innovative approaches have expanded our range of therapeutic options for percutaneous catheterization for branch pulmonary artery stenosis –15. Howe® Angel™) has shown excellent mechanical performance and biocompatibility . Mean TAPSE and S’ values increased after relieving pressure overload, although there were no significant differences due to small samples. Several previous studies have reported similar results in patients who underwent cardiac surgery; for example, one study showed that the values of TAPSE and S’ were increased in volume overload and decreased in pressure overload  and right ventricular systolic and diastolic function during the initial three months, the follow-up was too short since here after three months most of all the biodegradable stents were still there. Secondly, the relatively small size of the cohort may have biased the results. Finally, there was a lack of guidance for the assessment and quantification of RV function in congenital heart diseases in pediatric patients. Although MRI is the gold standard, it is still difficult to complete MRI examination for infants in China. The image quality of MRI is poor due to the long operation time, the difficulty for infants to cooperate and the need for sedation. 2D or 3D RV speckle-tracking echocardiology is the focus of future research. Clinical applications of strain imaging to assess systolic and diastolic function in children with complex congenital heart disease have recently been reported. However, the mean values and associated variations of these strain values have not to be firmly established in children, which limited the study.The prospective and multicenter clinical trial had some limitations. First, our follow-up period was two years, however, the preliminary trial only evaluated the efficacy and safety of stenting for branch pulmonary artery stenosis using a biodegradable nitride iron stent (IBSIn this preclinical trial, we first evaluated the efficacy and safety of IBS for branch pulmonary artery stenosis in children. The short-term results indicated that the biodegradable Fe- based stent is the perfect choice for infants or children. The diameter of the lumen was significantly improved and no stent thrombosis, malposition, or restenosis were observed. Nevertheless, small improvements in RV systolic and diastolic function were noted after successful transcatheter intervention, although there were no significant differences due to the small sample size. We believe that a comprehensive evaluation is now necessary in patients with biodegradable Fe-based stents, including the assessment of long-term safety, exercise capacity and ventricular function. Importantly, not all patients with branch PAS benefit from endovascular stenting; further evaluation is desirable to understand and predict whether intervention is likely to be beneficial.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Clinical Research Ethic Committee of Guangdong Provincial People’s Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.LS and J-jL contributed to conception and manuscript writing. Y-kX, Y-mX, and S-sW contributed to design and formal analysis. Z-wZ contributed to editing, supervision, and funding acquisition. All authors contributed to manuscript revision, read, and approved the submitted version.


Experimental data on pulmonary regurgitation has linked right ventricular longitudinal function to left ventricular filling pressure in animals with induced and treated pulmonary regurgitation but this relationship has not been investigated in patients with repaired Tetralogy of Fallot (rToF). The aim of this study was to determine if right ventricular longitudinal function assessed using cardiovascular magnetic resonance (CMR) is associated with left ventricular filling pressure in patients with rToF. A second objective of this study was to determine if direction of septal movement is related to right ventricular pressure load in rToF. Eighteen patients with rToF undergoing CMR and heart catheterization prior to pulmonary valve replacement were retrospectively included and catheter-based pressure measurements were compared with CMR-derived RV regional function. Left ventricular filling pressure was measured as precapillary wedge pressure (PCWP). Longitudinal contribution to RV stroke volume correlated with PCWP  but not with RV EF or pulmonary regurgitation. Neither RV longitudinal strain nor TAPSE showed correlation with PCWP. Longitudinal contribution to stroke volume was lower for the RV compared to the LV . Direction of septal movement did not show a correlation with RV end-systolic pressure. Right ventricular longitudinal pumping is associated with left ventricular filling pressure in rToF-patients and this inter-ventricular coupling may explain LV underfilling in patients with pulmonary regurgitation and rToF and may be of value to determine right ventricular dysfunction. RV systolic pressure, however, cannot be assessed from the direction of septal movement, in these patients. Tetralogy of Fallot (ToF) is one of the most common complex congenital heart defects. After initial surgical correction early in life many develop progressive right ventricular (RV) systolic dysfunction and RV dilatation . Right vDepending on type of initial repair and the morphological appearances of the RV outflow tract, pulmonary valve (PV), and pulmonary artery or conduit, ToF might include right ventricular outflow obstruction, pulmonary stenosis (PS), pulmonary regurgitation (PR) or a combination thereof . PulmonaThe right ventricle in rToF can be exposed to exaggerated pressure load , volume Experimental data on pulmonary regurgitation has linked RV longitudinal function to left ventricular filling pressures . Kopic eIn this study we aimed to elucidate further the relationship between invasive pressure measurements and RV regional function as well as direction of septal movement in a cohort of patients with rToF. We hypothesized that RV longitudinal pumping is related to the filling pressures of the left ventricle in this category of patients and that there is no correlation between direction of septal movement and pressure load of the RV.Retrospective inclusion of patients with rToF undergoing cardiac catheterization and CMR imaging prior to scheduled pulmonary valve replacement. Indications for PVR included RV dilatation, clinical symptomology due to stenosis, and invasive pressure indices. This retrospective aspect of the study was approved by the Johns Hopkins Institutional Review Board.Right heart catheterization by femoral venous access using a 5–7 French Balloon wedge-pressure catheter  included measurements of oxygen saturation and pressure. A pressure drop across the pulmonary valve of more than 30 mmHg was classified as pulmonary stenosis. Pulmonary hypertension was defined as a transpulmonary pressure greater than 12 mmHg. Pulmonary capillary wedge pressure was measured in the left pulmonary artery, right pulmonary artery, and if applicable in the conduit from primary surgery.Cardiac magnetic resonance imaging was conducted using a Siemens 1.5 T  with retrospective ECG gating at end-expiratory breath hold. Cine imaging was acquired with a steady state free precession sequence with typical repetition echo time: 1.25 ms, flip angle: > 50°, spatial resolution: 1.3 × 1.3 × 6 mm and typical temporal resolution of 30 ms. A stack of images covering the left ventricle in the short axis as well as images in the long axis views were acquired. In addition, phase contrast velocity mapping was acquired in the main pulmonary artery to quantify pulmonary regurgitation.http://segment.heiberg.se) . To determine interventricular relationships, paired Wilcoxon test (non-parametric) was used. Association between variables were analysed by Pearson correlation. A P-value of < 0.05 was considered statistically significant.Table Cardiac magnetic resonance imaging was performed at age 17 years [14–28 years] with time after initial total correction 15 years [12–21 years] . Catheter measurements were obtained between May 2010 and January 2019. CMR acquisition was performed between August 2009 and August 2017.All patients had PVR performed following CMR. Out of 10 patients who had RVEDVi < 140 ml 8 had pulmonary stenosis  as their indication for PVR. Two patients qualified for PVR due to a combination of RV dysfunction, pulmonary regurgitation and borderline RVEDVi.Table Longitudinal contribution to RVSV was lower  than longitudinal contribution to LVSV . Two patients did not contribute with values for TAPSE and one patient did not contribute with longitudinal strain, this due to insufficient CMR coverage .Figure Recordings of PCWP were performed in both the left and right pulmonary artery (PA) n = 3), left PA only (n = 10) or right PA only (n = 5). Pulmonary artery pressures were recorded in the pulmonary branches (n = 18) and in the main pulmonary artery or the surgically placed conduit (n = 14). Right ventricular pressure was obtained in all patients. Pressure drop across the pulmonary valve was 33 mmHg [16–49 mmHg]. 10 patients were characterized as having pulmonary stenosis (> 30 mmHg pressure drop). The transpulmonary gradient was 9 mmHg [7–11 mmHg], with two patients showing a transpulmonary gradient > 12 mmHg consistent with pulmonary hypertension. See Table , left PAA moderate positive correlation was found between longitudinal contribution to RV stroke volume and LV filling pressure measured as PCWP  as presented in Fig. Septal contribution to SV was − 2 ml [− 3.8–2.1]. Seven patients had positive values indicating movement towards the LV and thus septal contribution to LVSV. Eleven had negative values indicating movement towards the RV and thus septal contribution to RVSV. As illustrated in Fig. Septal volume indicating movement towards the LV in systole showed a weak positive correlation with longer QRS-duration , illustrated in Fig. This study addresses the hemodynamic relationship between LV filling pressures (measured as PCWP) and longitudinal RV pumping in patients with rToF. In addition, we investigate the direction of septal movement and its relation to RV end systolic pressure. Right ventricular longitudinal contribution to SV and left side filling pressures showed a moderate positive correlation. These results show that the previous experimental findings of a correlation between RV longitudinal function and LV filling pressure, measured as PCWP, in the setting of PR  are applAs long-term survival with rToF is improving, the importance of understanding the hemodynamics of these congenital heart defects become apparent  while tiWe sought to study RV longitudinal function in relation to LV filling as further indices to evaluate biventricular function in rToF is needed. RV dilatation has long been used as a marker of declining ventricular function in rToF, but recent findings suggest that this may be too simplistic. Rashid and colleagues highlighted this and showed that RV systolic function was more important for exercise capacity (an ultimately cardiac-output-dependent variable) than RV dilatation in rToF . TAPSE, . [In 2014, Stephensen et al.  studied . . Lower aQuantification of left sided filling pressure using precapillary wedge pressure is used clinically when a left heart catheterization is not available, but LV end-diastolic pressure (LVEDP) is considered the gold standard measurement of LV filling pressure. Precapillary wedge pressure do underestimate LVEDP, and is affected by pulmonary congestive disease more so than LVEDP , 21. One. showed that volume load affects longitudinal pumping in an experimental model where isolated PR lead to decreased longitudinal pumping and when pulmonary valve integrity was restored  longitudinal pumping increased once again [Kopic et alce again . The samce again , howeverce again . Thus, v. could be attributed to the use of an animal model rather than a heterogenous patient cohort. No correlation between degree of PR and PCWP could be shown in this study in patients with rToF nor in the above-mentioned experimental study of PR. Instead, PCWP was only related to RV longitudinal function and this suggests that patients with the same size pulmonary regurgitant volume reacts differently with regards to longitudinal function. As mentioned previously the correlation between increased RV longitudinal contribution to SV and increased PCWP could potentially be, at least partly, due to restrictive properties of the left atria and ventricle, thereby putting a greater “demand” on the RV pumping capacity to uphold filling. To what degree scarring and constrictive physiology of the ventricles after open heart surgery results in raised RV longitudinal contraction remains to be studied.In this study we found that RV longitudinal contribution to stroke volume is related to PCWP, with greater longitudinal contribution being related to higher filling pressures of the left ventricle. The same correlation was indeed observed by Kopic et. al in a porcine model of isolated PR , and oneThe current results suggests that RV longitudinal function may be of importance for the filling of the left atria and left ventricle, regardless of volume load on the RV. This notion is strengthen in the light of previous studies showing lower left atrial volumes and left ventricular volumes (lower LVEDV) using echocardiography , 25 as w. We would therefore conclude that septal movement is a less reliable indicator of ventricular function when there is a combination of volume- and pressure load, such as in the case of combined pulmonary insufficiency and stenosis. Surgical patch closure of a ventricular septal defect in rToF may affect interpretation of septal mechanics, as well as asynchronous contraction of the septum due to right bundle branch block, the latter being illustrated in Fig. Paradoxical septal movement towards the right ventricle during systole, was seen in a majority of patients included in this study. Paradoxical septal movement in rToF have previously been shown to be associated with lower LVEF  and is a5The cohort studied is a heterogenous one from a tertiary referral centre which may limit generalisability. However, this is often the case when studying seldom occurring congenital heart defects. In this study we did not have sufficiently large patient numbers to conduct subgroup analyses, such as for example for different surgical techniques. This is a major area of discussion as constrictive physiology following open heart surgery may affect intracardiac pressures. Also, both pulmonary stenosis and regurgitation was present in our cohort contributing to the heterogeneity. CMR and catheterization were not carried out simultaneously, therefore we cannot account for changes in hemodynamic properties during the time elapsed between assessments. For example, a continuous deterioration of RV function has been described in rTOF and it can be argued that this might be the case in the studied cohort during the time in between CMR and catheterization and we acknowledge this as a major limitation.Two patients had pulmonary arterial pressures consistent with definitions of pulmonary hypertension and how concomitant pulmonary vascular pathology might influence the correlation between RV longitudinal function and left sided filling pressures is yet to be determined in this population.Finally, interobserver variability is an issue when interpreting CMR images for determination of ventricular volumes, this has however been tested and proven robust for the above methods .Right ventricular longitudinal pumping is associated with left-sided filling pressures in rToF patients but not related to degree of volume overload (RVEF and PR). This is hypothesis generating and suggests that the longitudinal motion of the right ventricle could be viewed as an adaptive mechanism regardless of degree of volume load. Measuring RV longitudinal contribution may be of value when evaluating ventricular dysfunction in rToF-patients. Furthermore, direction of septal movement is an unreliable indicator of RV pressures in rToF patients probably due to combined pulmonary insufficiency and stenosis together with conduction abnormalities following open heart surgery. Care should be taken when interpreting septal movement in the setting of rToF.


COVID 19 pandemic has induced a large sedentarism in several kinds of sports. Some peculiar categories of athletes could particularly suffer from a prolonged inactivity as those affected by minimal cardiopathies as bicuspid aortic valve (BAV) athletes. This study aims to verify the myocardial performance in a restricted group of BAV athletes compared to a control group of agonistic athletes evaluated by traditional echocardiography and deformation parameters. 2D standard and deformations parameters were measured at rest conditions in BAV athletes and controls. Particularly EF, LVDD/LVS diameters, GLS rotation and twisting were considered as myocardial performance data; E/A, E1 and A1 as diastolic ones. All the 2D standard parameters measured were within the normal range in both groups, especially the EF value. Significant differences were found in the diastolic function with reduced values of E and E1 waves in BAV vs. controls. The strain analysis showed a significant reduction in GLS measured in 2C, 3C, 4C in BAV if compared to controls, while no significant differences were found in torsional and rotational parameters. These results are suggestive for a potential long term negative impact of inactivity on cardiac performance more evident in BAV athletes, if compared to athletes with normal aortic valve. GLS of LV and RV can be considered as a predictive parameter of this mild dysfunction and assumed as follow-up parameter to restore a progressive training. The COVID 19 pandemic led to considerable restrictions in the sports field, reducing the hours of daily physical activity and therefore causing a worsening of lifestyle.Some categories of sport participants under particular surveillance for minimal heart disease may suffer from the negative effects of these restrictions. The forced confinement could potentially induce to a cardiovascular risk factors accumulation and worsening the basic myocardial performance.Among them, the athletes with bicuspid aortic valve (BAV) and mild valvular dysfunction, eligible for sports activity, are particularly interesting in sport medicine. Previous studies have defined the evaluation of sport fitness criteria and also the specific aspects of cardiac performance ,2. In paThe study aimed to verify, during the period of the COVID19 pandemic, the myocardial performance among athletes with Bicuspid Aortic Valve in absence of regular training and reduced lifestyle level, assessed with echocardiographic evaluation. They have been compared to a group of athletes practicing high intensity sports, equally forced to sedentarism. The study has been planned in order to evaluate the eventual peculiar impact of a prolonged sedentarism on this specific category of subjects in absence of effective aortic valve dysfunction.A group of 29 BAV athletes  and a control group of 16 young athletes practicing rowing , similar for intensity of training, were selected for a cardiovascular examination by echocardiographic exam conducted at resting condition. At the time of the investigation, none of the participants received the vaccination against SarsCov2 and they were forced to prolonged sedentarism as a consequence of COVID-19 pandemic. None showed acute cardiovascular or respiratory symptoms.Among BAV athletes, 5 practiced athletics, 2 basketball, 16 soccer, 3 swimming, 1 cycling and 1 fencing.Following the ESC guidelines valve classification , BAV morThe 2D echo examination was performed by two certified sonographers. It included the standard systo-diastolic and the deformation parameters as global longitudinal strain, basal and apex rotation and torsion of the left ventricular chamber.Considering the data were from the institutional database, normally obtained during the annual check sport medicine eligibility, in this case the ethical commitee approval is not mandatory. An informed consent was however distributed among the participants. A written informed consent has been obtained from the patients.2) was obtained using the Devereux formula [Following the American Heart Association Guidelines,  a comple formula . Ejectio formula . Morphol formula .The 2D images of 4-chamber views were post-processed with X-Strain software to provide an angle-independent tool for the evaluation of velocities and strain. This software allows automatic evaluation of the dynamic properties of the endocardial border and of the sub-endocardial tissue from 2D B-mode echocardiographic clips. Strain analysis by speckle-tracking is independent of translational motion, tethering effects of the nearby regions, and it thus allows uniformity of measurements through the normal LV myocardium.The endocardial border is drawn by the operator in a four-chamber view on a single frame from one annulus to another; the first and last points delineate the mitral plane. The other regional segments points were automatically set by the dedicated software. The LPSS was measured in basal and mid-apical segments of the LW and IVS from the images captured at rest The focused apical 4-chamber view was used for the LV and a modified apical four-chamber view for the RV. In both views frame rates were adjusted to between 40 and 90 frames per second.During the offline analysis  a region of interest was placed around the LV from basal septum through to the basal lateral wall ensuring the whole of the myocardium was encompassed within. This provided six myocardial segments and an average of these provided a global index of LV longitudinal ε. For the RV the Offline analysis involved placing the region of interest around the RV lateral wall only from base to apex. From the short axis view, captured at basal and apex segments of the LV chamber, the rotation was calculated. The net difference of the basal vs. apex rotation values, gave the torsion. Tecnically from that window an as-circular-as-possible short-axis image of the LV apex, just proximal to the level with end-systolic LV luminal obliteration, was obtained by angulation of the transducer. The short-axis views, captured at the mitral valve plane and apex level, were later on processed by the speckle tracking X-Strain software. The software asks the operator to provide the initial position of the tracking points.p) of 0.05 was considered statistically significant. Two-sided 95% exact confidence intervals were used to estimate the difference in the two groups, which is consistent with the two-sided significance level of 0.05.All data are reported as mean + SD. The comparisons between LPSS values of basal and mid-apical segments for each group were performed using Student’s unpaired t-test . A probability value (p < 0.01). Demographical data are expressed in 45 subjects (29 BAV athletes and 16 rowers) were included in the study. The two groups did not differ for weight, height, BMI and BSA. Instead, there was a significant difference in mean age of the two groups  and an higher A wave value  than rowers, resulting in an E/A ratio lower in BAV group . Besides, BAV group presented lower values of E1  but had higher values of A1  and S waves . There were no significant differences regarding the aortic measures, with the exception of the diameter of aortic bulb, which was significantly higher in BAV group . Evaluating right ventricle echocardiographic parameters, RV area resulted higher in the BAV group  while the Rvot, basal and longitudinal diameter values were higher in rowers .No significant differences were reported for LV diameters, wall thicknesses and cardiac mass ; the groOther significant differences were detected at speckle tracking analysis : rowers BAV is a common congenital heart disease normally compatible with the sports activity ,2,9. ProA first consideration must be made about the age difference between the two groups: although significant, the difference between mean age of BAV athletes and rowers was about 8 years, which is a relative short amount of time to determine a significant impact on cardiac remodeling, in agreement with what was already described in literature ,12. In aA specific attention has been dedicated toward the rotation and twisting. These parameters play a relevant role in the characterization of the heart performance in adaptive ,14 and mAlthough the evidence of the same and normal LV systo-diastolic diameters and EF in both groups, a potential different micro-structural remodelling of the heart could justify this specific behaviour. No data of the previous echocardiographic condition have been reported in the present investigation, considering the early past of the athletes, was in absolute normal conditions: they had obtained infact the eligibility. No myocardial strain analisys have been made in that time, considering the deformation parameters are not comonly used routinarly. Deformations parameters are more subtle and sensitive in the early detection of the fibres impairment, compared to standard EF evaluation ,18. Our Despite torsional and rotational parameters reduction appears to go in the same direction of athletes detraining, decreasing values of GLS could be associated to initial cardiac disfunction also in apparently healthy subjects. The data obtained support the importance to perform a complete echocardiographic evaluation in sports medicine, especially after the reduction of the amount of physical activity. Strain analysis can add specific informations on the heart’s function.Cardiac function could be negatively affected during a prolonged period of sedentarism or forced reduced physical activity. This specific aspect will need to be more in deep investigated by a long tern follow –up, not applicable in a time of a reduced access to a medical center due to the high level virus infection. Among athletes affected by minor congenital cardiac disease and therefore generally considered within the eligibility, the BAV athletes are a special category under peculiar cardiologic attention long known. The present investigation support the hypothesis to focus on a particular population of athletes normally studied only for their sport performances. Despite regular physical activity plays an important role in general population, our findings suggest that BAV population may particularly benefit from regular training in a more relevant way. Especially, speckle-tracking exam can offer the possibility of detecting subtle contractile impairment: in fact, among strain parameters, GLS was reduced. An eventual role of the moderate intensity of training vs. high intensity in this category of athletes, with particular attention on spontaneous physical activity, will need more investigations in future.The principal limits of the study is the small size of the sample, justified in any case on the basis of the difficulties to enroll a wide group in the COVID pandemia period when a strong restriction of the physical activity had been made, especially in sport medicine.An other limit is due to age difference of the two groups investigated that is, in any case, on the basis of the level of training, not in first line considered determinant of the principal aim of the study, addressed to strain analysis that cover a larger age range if compared to the 2D standard echo parameters.


Myocardial edema is an early manifestation of chemotherapy-related myocardial injury. In this study, we used cardiac magnetic resonance (CMR) T2 mapping to assess myocardial edema and its changes during chemotherapy for gynecologic malignancies.We enrolled 73 patients receiving chemotherapy for gynecologic malignancies, whose the latest cycle was within one month before the beginning of this study, and 41 healthy volunteers. All participants underwent CMR imaging. Of the 73 patients, 35 completed CMR follow-up after a median interval of 6 (3.3 to 9.6) months. The CMR sequences included cardiac cine, T2 mapping, and late gadolinium enhancement.Myocardial T2 was elevated in patients who were treated with chemotherapy compared with healthy volunteers . During follow-up, myocardial T2 rose further . Multivariate analysis showed that the number of chemotherapy cycles was associated with myocardial T2 elevation . After adjustment for other confounders, myocardial T2 elevation was independently associated with a decrease in left ventricular mass .In patients with gynecologic malignancies, myocardial edema developed with chemotherapy cycles increase, and was associated with left ventricular mass decrease. T2 mapping allows the assessment of myocardial edema and monitoring of its change during chemotherapy. All participants provided written informed consent forms before enrollment. Patients from the Department of Tumor Radiation and Chemotherapy who were diagnosed with gynecologic malignancies were recruited. Inclusion criteria were (1) current or recent (within the preceding month) receipt of chemotherapy and (2) age between 18 and 75 years . ExclusiWe obtained venous blood samples from patients 1 hour before CMR imaging to examine serologic markers of myocardial injury, including troponin I and creatine kinase.2. T2 mapping images were acquired using the steady-state free-precession technique, and three single-shot images were acquired at different T2 preparation times . The detailed parameters were as follows: TE = 1.23 ms, TR = 38.34 ms, flip angle = 60°, slice thickness = 8 mm, matrix = 208 × 208 pixels, and FOV = 250 × 300 mm2 . The CMR protocol consisted of cardiac cine, T2 mapping, and late gadolinium enhancement (LGE) imaging. Cine imaging used a balanced steady-state free-precession pulse sequence: echo time (TE) = 1.22 ms, temporal resolution (TR) = 39.34 ms, flip angle = 40°, slice thickness = 8 mm, matrix = 208 × 208 pixels, and field of view (FOV) = 340 × 284 mm 300 mm2 . For LGETwo experienced radiologists separately conducted the image analysis using imaging postprocessing software . The analysis of LV functional parameters was presented in previous studies . MyocardTo assess intraobserver variability, one radiologist randomly measured myocardial T2 in 39 subjects twice within 1 week. The other radiologist, who was blinded to the first radiologist’s results, then reperformed the measurements.t-test or the rank-sum test was used to compare continuous variables between patients and healthy volunteers, as appropriate. Parameters from the two CMR examinations, performed in 35 patients who completed CMR follow-up, were compared using the paired t-test or rank-sum test, as appropriate. Bivariate correlation analysis was performed using the Pearson’s or Spearman’s method, as appropriate. To identify the factors that were independently associated with myocardial T2 and LV mass, a multivariate linear regression model was constructed. Intraobserver and interobserver variabilities of myocardial T2 measurements were assessed using intraclass correlation coefficient. All tests were two tailed; P values < 0.05 were accepted as statistically significant.Statistical analysis was performed using IBM SPSS Statistics  and GraphPad Prism  software applications. Categorical or enumeration parameters were presented as numbers (percentages), whereas continuous variables were expressed as the mean ± standard deviation or as medians (interquartile range), as appropriate. The chi-square test was used to compare categorical or enumeration parameters. The independent P > 0.05). Moreover, no cardiovascular diseases or cardiovascular risk factors were detected in any of the enrolled volunteers.From September 2018 to December 2020, this study enrolled 73 patients treated with chemotherapy for gynecologic malignancies and 41 healthy volunteers Figure 1Among the 73 patients treated with chemotherapy, 6  were complicated with hypertension and 3  had diabetes. In addition, 6 patients  had a history of taking cardiac medication Table 1.Of the 73 patients, 35 patients  completed the CMR follow-up. The interval between the two scans was 6 (3.3 to 9.6) months, and these patients completed 3 (2 to 5) cycles of chemotherapy during the interval.P > 0.05). However, the LV mass  and LV end-diastolic volume  were slightly lower in patients compared to healthy volunteers. Among 73 patients, 17  were recorded as positive for LGE, as opposed to healthy volunteers who were all negative. At CMR follow-up in 35 patients , and three patients were newly recorded as positive for LGE .For LV functional parameters Table S1P = 0.013], whereas myocardial T2 showed no difference in the middle and basal slices between the two groups (both P > 0.05).The global LV myocardial T2 was higher in patients than in healthy volunteers  and troponin I .However, no correlation was observed between myocardial T2 and creatine kinase  or troponin I .In the 35 patients who completed CMR follow-up, the myocardial injury biomarkers tended to increase from baseline to follow-up imaging: creatine kinase [39u/L (15u/L to 41u/L) vs. 78.00u/L (58.25u/L to 95.00u/L), Univariate analysis indicated that both the receipt of chemotherapy  and chemotherapy cycles received  positively correlated with myocardial T2 in all subjects. In model 1, after adjustment for chemotherapy drug types and time interval from first chemotherapy to CMR imaging, the number of chemotherapy cycles was associated with myocardial T2 . When Model 2 added age and clinical risk factors to the analysis, the number of chemotherapy cycles was also associated with an increase in myocardial T2 . In the multivariate analysis, after adjustment for CMR parameters and clinical risk factors , myocardial T2 remained independently associated with a reduction in LV mass  and 0.904 (95% CI: 0.818–0.950), respectively.This study enrolled patients treated with chemotherapy for gynecologic malignancies and used CMR T2 mapping to assess myocardial edema. The main findings were the following (1): Myocardial T2 was higher in patients than in healthy volunteers and increased as the chemotherapy cycles received increase during follow-up. (2) After adjustment for chemotherapy drug types and clinical characteristics, the number of chemotherapy cycles was associated with increased myocardial T2. (3) In the multivariate analysis including CMR and clinical risk factors, increased myocardial T2 was independently associated with lower LV mass. To the best of our knowledge, the present systematic study is the first to focus on myocardial edema associated with chemotherapy for gynecologic malignancies. Most patients included in this study underwent chemotherapy with paclitaxel plus platinum, a combination that is infrequently reported in literature. Our results showed that myocardial edema could be aggravated as chemotherapy continues and that myocardial edema is associated with a reduction in LV mass. Thus, the cardiac side effects of paclitaxel and platinum chemotherapy require clinical attention. Using CMR T2 mapping, clinicians can assess myocardial injury and track changes of myocardial edema during chemotherapy.Chemotherapy-related cardiotoxicity develops because of a variety of physiological changes, and myocardial edema is an early manifestation –9. QuantAdditionally, our study revealed that the increase in myocardial T2 of patients was more pronounced in the apical slice than in the middle and basal slices. Although similar data haven’t been reported about the regional distribution of myocardial T2, published literatures have demonstrated the greatest motion impairments at heart apex in patients treated with chemotherapy , 27. TakAs reported in the previous studies, myocardial T2 varies with the individual, and is potentially influenced by factors such as age and sex –30. LongTo date, clinical studies have focused mostly on the cardiotoxicity caused by anthracyclines and/or trastuzumab –9, 32–34During chemotherapy for cancer, the left ventricle can undergo a series of morphological changes, and those changes have prognostic significance –5. SeverThis study has several limitations. (1) This single-center study had a relatively small sample size. Nevertheless, the findings demonstrated that T2 mapping can be used to assess myocardial injury in patients undergoing chemotherapy for gynecologic malignancies. Future studies with larger populations are needed to strengthen our findings. (2) Most enrolled patients were at critical condition, meaning that they had to start chemotherapy as soon as possible. Consequently, a baseline CMR examination before chemotherapy was not performed. Given that situation, we recruited healthy volunteers to act as a control group. (3) Because the experiment was conducted during the COVID-19 outbreak, some patients contracted the virus, and thus, the rate of follow-up in the study was low. Future studies with larger cohorts are required to investigate whether myocardial T2 can predict a reduction in LVEF. (4) Our patient cohort received several different chemotherapy regimens. Although the effect of chemotherapy on myocardial edema was adjusted for drug types, the individual effects of the various drugs require further elucidation. (5) This study didn’t measure N-terminal pro-B type natriuretic peptide in patients, the association between N-terminal pro-B type natriuretic peptide and myocardial T2 needs further study with longer follow-up.In patients receiving chemotherapy for gynecologic malignancies, myocardial edema develops with the increase of chemotherapy cycles received. The myocardial edema is associated with a reduction in LV mass. T2 mapping allows the assessment of myocardial injury and the monitoring of myocardial edema during chemotherapy.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.The clinical protocol of this study was approved by the institutional ethics review board of West China Second Hospital and Chinese Clinical Trial Registry (ChiCTR-DDD-17013450). The patients/participants provided their written informed consent to participate in this study.Conceptualization, Y-KG and Z-GY; methodology and formal analysis, M-XY, XL, and LY; data curation and investigation, Q-LL, D-QW, and K-ML; supervision, R-TY and X-JL; original draft, M-XY and XL; review and editing, X-SL, CF, and X-MM; guarantor, Y-KG. All authors contributed to the article and approved the submitted version.This work was supported by National Natural Science Foundation of China ; Sichuan Science and Technology Program ; Fundamental Research Funds for the Central University (SCU2020D4132); Clinical Research Finding of Chinese Society of Cardiovascular Disease of 2019 (HFCSC2019B01) and 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University .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.


Background: As methamphetamine use has increased around the world, cardiovascular mortality has also increased. Methamphetamine-associated cardiomyopathy (MACM) is one of the serious cardiovascular complications of methamphetamine use. Limited evidence has been published regarding the increased risk of thrombogenicity in the setting of methamphetamine use. We propose that increased thrombogenicity presents a risk factor for intracardiac thrombi.Case Report: A 48-year-old female with a history of MACM was admitted to the hospital with acute decompensated heart failure. Transthoracic echocardiogram revealed multiple biventricular masses requiring further workup, but the patient left against medical advice on warfarin. The patient presented again 2.5 months later with decompensated heart failure. During the second admission, cardiac magnetic resonance imaging (CMR) characterized the masses in the left ventricle as thrombi, and computed tomography of the chest with contrast showed pulmonary embolism. Although the right ventricle mass was not seen on CMR, we believe the mass was a thrombus that either had migrated into the lungs or had resolved with warfarin use.Conclusion: MACM and biventricular thrombi are associated, but the association is rare and not well studied. Although the exact mechanism of this association is unknown, the increased circulating catecholamines are believed to be a contributing factor for increased thrombogenicity in the setting of active methamphetamine use. We suggest keeping a low threshold for surveillance echocardiography to screen for intracardiac thrombi in MACM patients with active methamphetamine use when they present with even mild symptoms of decompensated heart failure. Other relevant history included active tobacco use disorder, active methamphetamine use, hypothyroidism, and frequent heart failure hospitalizations because of dietary and medication noncompliance. Family history was negative for thrombophilia. Initial vital signs were significant for tachycardia with a heart rate of 120/min, borderline hypotension with blood pressure of 89/90 mm Hg, and tachypnea with a respiratory rate of 28/min. Laboratory results were significant for troponin elevation of 0.208 ng/mL . Workup for nonischemic cardiomyopathy was unrevealing. Ferritin, iron, iron saturation, thyroid-stimulating hormone, antinuclear antibody, hepatitis C antibody, urine and serum protein electrophoresis, and HIV screen were normal. Because antinuclear antibody was normal, further workup for lupus was not pursued. Hypercoagulable workup with rotational thromboelastometry was also normal. Electrocardiogram was without ischemic changes but showed QTc prolonged at 520 milliseconds and left atrial enlargement .Two years prior, coronary angiography had shown normal coronary arteries.2, right ventricle of normal size, grade III diastolic dysfunctions, severe global hypokinesis, and at least 4 masses in the left ventricle and 1 mass in the right ventricle (Transthoracic echocardiogram (TTE) showed left ventricular ejection fraction of 18%, severely dilated left ventricle with left ventricular internal dimension at end diastole index of 3.93 cm/mentricle  and 3. BApproximately 2.5 months later, the patient presented again with decompensated heart failure. At this time, she presented with a heart rate of 130/min and hypoxia requiring 4 L oxygen. Computed tomography (CT) chest with contrast revealed right lower lobe segmental pulmonary embolism. She was initially started on therapeutic dose heparin and was later switched to warfarin. Repeat TTE at this admission showed severely reduced left ventricular systolic function with ejection fraction of 18% and 2 left ventricular masses. CMR obtained during this admission characterized the left ventricular masses as thrombi but showed no evidence of malignancy or infection . Right v2 The incidence of MACM among methamphetamine users increased from 1.8 percent in 2009 to 5.6 percent in 2014.4 The underlying mechanisms include the replacement of myocytes by fibrosis and myocardial contractile dysfunction caused by a combination of catecholamine-induced myocardial wall stress and methamphetamine-induced direct myocardial cell toxicity.5Cardiovascular complications of methamphetamine use are well established and include malignant hypertension, arrhythmias, aortic dissection, myocardial infarction secondary to vasospasm, stroke, pulmonary arterial hypertension, and cardiomyopathy.6 Patients with MACM have a 33% prevalence of developing left ventricular thrombus and a 3.3% prevalence for developing right ventricular thrombus,5 likely attributable to a combination of increased catecholamine activation, prothrombotic state, and severe cardiac dysfunction.2 Sympathetic catecholamines have been shown to cause platelet aggregation in vitro and to enhance thrombus formation in plastic shunts in vivo.7 The aforementioned factors contribute to the increased risk of intracardiac thrombus burden seen in MACM patients.Patients with MACM tend to be younger than patients with cardiomyopathy attributable to other causes. Patients typically present with severe heart failure, reduced ejection fraction, and compensatory tachycardia in the setting of low cardiac output. The usual echocardiogram findings are severe left ventricular dilatation, reduced systolic function, right ventricle dilatation, and global left ventricle hypokinesis.3 However, compared to the case reported by Janardhanan and Kannan,3 our case is unique in several ways. First, biventricular thrombi associated with MACM are rarely reported, especially with simultaneous pulmonary embolism. We believe the right ventricular thrombus migration was the cause of pulmonary embolism in our patient, which highlights the instability of the thrombus. Second, given the patient's tachycardia and borderline hypotension, we repeated the TTE during the second hospitalization as opposed to the usual management of not obtaining TTE during heart failure–related readmissions. This management approach was a judgment call that perhaps prevented a fatal event, such as pulseless electrical activity cardiac arrest from pulmonary embolism or embolic phenomenon including stroke, by starting the patient on anticoagulation during her first hospitalization. Based on the limited evidence and our case, we suggest prophylactic anticoagulation for patients who are actively using methamphetamine and have MACM, severely depressed ejection fraction, and severe left ventricle dilation.In our case, we believe the right ventricular mass seen on TTE during the initial hospitalization was a thrombus as its appearance and echocardiogram density were similar to the echocardiogram density of the masses seen in the left ventricle. We believe the reason the right ventricular mass was not seen on CMR during the second admission is because the thrombus was small and had either resolved with anticoagulation or migrated into the lungs, causing the pulmonary embolism that was seen on the CT chest. To the best of our knowledge, ours is the second reported case of biventricular thrombi in the setting of MACM.Based on the literature and methamphetamine pathophysiology, we propose that in addition to the severe dilated cardiomyopathy, active methamphetamine use is not only a risk factor for intracardiac thrombi but can also lead to increased thrombus burden with biventricular involvement. Perhaps elusive mechanisms are involved that need to be investigated further. We suggest repeating TTE in patients with MACM and active methamphetamine use during every hospitalization as a surveillance strategy for biventricular thrombi, especially if a left heart catheterization is being considered, as many of these patients undergo this procedure. Anticoagulation with warfarin is advised as the mainstay of therapy to treat and potentially prevent the recurrence of the thrombi.