Impressively increasing availability of mechanical circulatory/cardiac support systems (MCSs) worldwide, together with the deepening of the knowledge of critical care medical practitioners, has inevitably led to the discussion about further improvements of intensive care associated to MCS. An appealing topic of the left ventricle (LV) overload related to VA ECMO support endangering myocardial recovery is being widely discussed within the scientific community. Unloading of LV leads to the reduction in LV end-diastolic pressure, reduction in pressure in the left atrium, and decrease in the LV thrombus formation risk. Consequently, better conditions for myocardial recovery, with comfortable filling pressures and a better oxygen delivery/demand ratio, are achieved. The combination of VA ECMO and Impella device, also called ECPELLA, seems to be a promising strategy that may bring the improvement of CS mortality rates. The series of presented trials and meta-analyses clearly showed the potential benefits of this strategy. However, the ongoing research has brought a series of new questions, such as whether Impella itself is the only appropriate unloading modality, or any other approach to unload LV would be beneficial in the same way. Benefits and potential risks of LV unloading and its timing are being discussed in this current review. Widely increased availability of mechanical circulatory/cardiac support systems (MCSs), together with the deepening of the knowledge of critical care medical practitioners, has inevitably led to the discussion about further improvements of intensive care associated to MCS. Cardiogenic shock (CS) is one of the main indications for using MCS, related to not only acute coronary syndromes but also myocarditis, end-stage heart failure, postcardiotomy, and other etiologies. CS is associated with significant hospital mortality . The appSince its introduction in 1972 , there hNevertheless, it is important to note that randomized controlled studies in this context are very challenging primarily due to logistical, legal, and ethical challenges associated with conducting such trials involving patients with cardiac arrest or severe cardiogenic shock. While some indications of improved survival and neurological outcomes have been observed in specific patient subgroups receiving ECPR for refractory cardiac arrest, these benefits are more prominent in cases of in-hospital cardiac arrests (IHCAs) and instances where immediate and effective bystander cardiopulmonary resuscitation is administered, with minimal delays in initiating VA ECMO .Overall, the reported survival rates with peripheral VA ECMO in cardiac arrest and refractory cardiogenic shock typically range between 29%  and 41% (for refractory cardiogenic shock) . Due to Implantation of VA ECMO is followed by a rapid restoration of tissue perfusion; this is obvious from the term mechanical circulatory support. Yet, the term mechanical cardiac support also exists, but it should not be used in the context of VA ECMO, as it provides no augmentation to the LV function. Therefore, it is more appropriate to save this term for left or right ventricular assist devices (LVADs/RVADs), which are actually able to provide support to myocardial function. Atti et al. (2022), in their comprehensive review, described various types and modifications of mechanical circulatory and cardiac support systems. In VA ECMO serves as a temporary mechanical circulatory support system with simultaneous external gas exchange for individuals facing acute cardiorespiratory failure. Each VA ECMO setup includes components such as a venous cannula (for inflow and drainage), a centrifugal pump, an oxygenator, and an arterial cannula (for outflow and return). VA ECMO cannulas can be inserted through either peripheral or central access methods. Central VA ECMO configuration can mainly be seen in cardiac surgery theaters to provide short-term assistance, typically for patients with postcardiotomy heart failure who are struggling to be weaned off cardiopulmonary bypass .On the other hand, peripheral VA ECMO can be initiated either percutaneously or through surgical intervention outside an operating room. This is typically reserved for patients experiencing refractory cardiogenic shock and cardiac arrest, with access via the femoral artery and femoral or internal jugular vein. Alternatively, a different approach utilizes standard venous access  with arterial return directed to an ascendent aorta via vascular graft . This cofemoral vein and artery are used) configuration. A venous cannula is inserted though the inferior vena cava directly to the right atrium; the blood is being drawn into the extracorporeal circuit and flows through the complex of an oxygenator and centrifugal pump to enter the return arterial cannula, which expels the blood flow retrogradely through the arterial system into the abdominal and thoracic aorta and provides perfusion to tissues and organs [A general approach for the implantation of VA ECMO under acute conditions is peripheral, bifemoral , a condition called Harlequin syndrome may ensue. Harlequin, or north–south syndrome is reported in 8.8% of cases [radial artery). Another possibility to detect hypoxic cerebral perfusion is the use of near-infrared-spectroscopy (NIRS) monitoring, attached to patient’s forehead [internal jugular vein and thus upgrading to V-AV ECMO to assure adequate oxygenation of the blood leaving the LV.Blood flow generated by VA ECMO is non-physiological. The blood stream is directed against the physiological flow (if any is preserved) in the aorta. Thus, two extreme conditions can emerge. If the LV function is maintained to some extent, then there is a meeting (mixing) point of the physiological and ECMO blood stream somewhere in the aortic arch. Thus, if the LV function is preserved enough to shift this mixing point distal from the origin of the of cases . Pathophof cases ,15. Not of cases . Owing tThanks to large bore cannulas and modern pumps, VA ECMO can provide substantial flow support; typical flows usually range around 3 to 4.5 L per minute. VA ECMO achieves this by directly drawing blood from the systemic venous system, which reduces the right ventricular preload and alleviates peripheral venous congestion. The flow rate (Q) is determined by the pressure gradient created by the pump and is significantly influenced by the cannula’s radius . Additionally, it is inversely proportional to fluid viscosity (η) and cannula length (l), as per Poiseuille’s law Q = πPr^4/8ηl [While it may seem that this redirection of blood away from the heart would also reduce the LV preload and alleviate pulmonary congestion, this is not the right understanding of the situation. This is partly due to the fact that ECMO, despite providing higher flows, elevates blood pressure. Consequently, even with the increased ECMO-induced arterial flow, some blood continues to flow through the pulmonary circuit . Factors such as the Thebesian drainage of coronary blood flow, the presence of aortic regurgitation, and the return of bronchial blood flow to the LA contribute to blood returning to the LV. To exit the LV, blood must overcome the ECMO-induced increase in arterial pressure, necessitating the LV to generate sufficient pressure .(1)increased end-diastolic LV pressure (LVEDP);(2)increased LV wall tension;(3)worsening of mitral valve regurgitation;(4)increased LA pressure;(5)elevation of pulmonary venous pressure;(6)increased risk of LV thrombosisIt is obvious that in patients with peripheral VA ECMO, it is not possible to completely drain the blood entering the heart; thus, residual basic circulation through the natural pathway still exists. This phenomenon may cause serious clinical issues in another extreme hemodynamic situation, which will be emphasized in this review. In case of severe LV dysfunction without any effective stroke volume, the impaired function of the LV is furthermore deteriorated by the increase in the afterload caused by the blood stream originating from the ECMO. As a consequence of this, typical hemodynamic pattern may ,13 be seEven if there would not be clinically significant deterioration in LV pulsatility, the pathophysiology connected to the adaptation of the LV to the increased afterload is working behind the scenes. Thus, firstly, LVEDP is increased, which is followed with increased calcium sensitivity of cardiomyocytes resulting in higher contractile power. These adaptation mechanisms, important for the preservation of the LV stroke volume despite the increased afterload, are tightly tied to a higher oxygen demand of the myocardium .Adjusting VA ECMO flow to the lowest sufficient value accompanied with thorough restrictive fluid management using diuretics, hemodialysis (CVVHD), or continuous veno-venous hemofiltration (CVVH) and inotrope agents might help with left heart decompression. However, this conservative approach might not be possible in most severe cardiogenic shock patients presented with a completely akinetic LV.Patients with aortic valve regurgitation and a competent mitral valve are logically more endangered with the LV overload. Considering another valve pathology, the presence of mitral valve regurgitation enables the transmission of pressure from an overloaded LV into the LA and pulmonary circulation (increase in PCWP (pulmonary capillary wedge pressure) and PAP (pulmonary artery pressure) is measured) resulting in the congestion and deterioration of oxygenation.extremis, when the leaflets of the aortic valve are not being opened, clinically presented as a non-pulsatile flow, the thrombosis of the aortic valve, aortic root, and LV may occur . Described alterations in the physiology of the heart may lead not only to the development of pulmonary edema (by the increase in pulmonary venous pressure) but even to the worsening of myocardial ischemia  and the frequency of malignant ventricular arrhythmias. These changes can be summarized in terms of increased mechanical stress and strain.In Detecting LV distention and pulmonary edema during VA ECMO support plays a crucial role in patient care. Various clinical indicators can be utilized to monitor and identify patients who may be at risk. Firstly, one straightforward approach involves assessing the presence and extent of aortic valve opening through arterial pulse pressure tracing. As ECMO flow increases, the mean arterial pressure rises, but the pulse pressure and stroke volume decrease, indicating a reduction in aortic valve opening .Secondly, echocardiography can provide direct visualization of the degree and duration of aortic valve opening. The use of an M-Mode through the aortic valve can help determine if and to what degree the aortic valve is opening. However, it is worth noting that when it comes to assessing LV distention, echocardiography may have limitations. This is because changes in LV dimensions may not accurately reflect changes in LVEDP due to the nonlinear nature of the LVEDP relationship and pericardial constraints . AdditioThirdly, progressive hypoxia in blood exiting the LV, which can be measured from the right radial artery or by cerebral oximetry, may indicate the perfusion of the upper circulation with deoxygenated blood due to worsening pulmonary edema  Lastly, (1)pharmacological management ;(2)surgical (vent in the LV/left atrium/pulmonary artery);(3)percutaneous devices  and percutaneous axial flow devices like the Impella family by Abiomed).Unloading of the LV seems to be a reasonable solution to preserve the LV function by decreasing the energy demand and possibly achieve better outcomes. Several modalities were described  for thisConsidering the surgical approach sternotomy or thoracotomy is usually used to place a venting cannula into the pulmonary vein, directly to the LV, left atrium, or even pulmonary artery. An obvious disadvantage of these methods is the degree of invasiveness and high risk of bleeding complications.Therefore, percutaneous methods with limited invasiveness have become most widely used. Nowadays, in 84% of cases, LV unloading was provided by percutaneous devices, and 16% of cases underwent surgical procedure in order to unload the overdistended LV [femoral artery; Impella 5.5 requires arteriotomy and a vascular graft.The Impella device is a catheter-based, small measured percutaneous axial flow LVAD, which is able to create a blood flow of up to 2.5/3.5/5.5 L/min depending on a particular type of the machine. The Impella family currently contains Impella CP, 5.5, and RP (for the right heart support) ,19. ImpeThe origin of the idea of how blood flow is created in Impella leads to the ancient Greece, where Archimedes’s screw was invented (approx. 200–300 BC). The American physician Richard Wampler, a father of the reborn idea, developed a predecessor of the Impella in 1985. After years of improvements, in approx. 2000, finally the Impella family of devices was revealed ,19.LV overload after VA ECMO implantation puts myocardial recovery in danger. Unloading of the LV leads to the reduction in the LV end-diastolic pressure, reduction in the pressure in the left atrium, and the decrease in the LV thrombus formation risk. To conclude, better conditions for myocardial recovery, with comfortable filling pressures and a better oxygen delivery/demand ratio, are achieved . Currentinternal jugular vein (for the return of oxygenated blood) and transformation to V-AV ECMO + Impella should be a solution to the issue [Drawbacks of using Impella are increased risk of bleeding complications, hemolysis, and abdominal compartment syndrome . Notablyhe issue .Impella family devices are contraindicated for patients with LV thrombosis, mechanical aortic valve prosthesis, moderate-to-severe aortic valve disease, and severe peripheral artery disease . The above-mentioned list of limitations is even more bounding in critically ill patients due to the higher frequency of these pathological conditions.p < 0.001) in-hospital mortality than patients with VA ECMO only [p < 0.01) against VA ECMO only [The pioneers of the new approach—Pappalardo et al.—published in 2017, the first worldwide, a retrospective observational study on 157 patients. The group with ECPELLA showed significantly lower . On the other hand, hemolysis  and RRT  occurred at a higher rate in the group of patients with ECPELLA. No significant difference was observed in terms of major bleeding complications between the groups  and cerebrovascular accidents  [Recent meta-analysis published by Fiorelli and Panoulas in 2021 included 972 patients, which were divided into the ECPELLA and ECMO-only groups. After excluding studies without a homogenous comparator group, the combination of Impella with VA ECMO was still associated with lower mortality risk  .p< 0.001) before the VA ECMO implantation also more often. However, importantly, in these basically more severely ill patients, a lower in-hospital mortality rate was observed , which remained lower in a multivariable modeling (adjusted OR (aOR): 0.84; 95% CI: 0.77–0.92; p < 0.001). What was not significant in this retrospective analysis is a mortality difference in the ECPELLA vs. VA ECMO + IABP group  [A huge retrospective study performed based on ELSO registry by Grandin et al. in 2022 showed an even wider image of LV unloading. The big data from ELSO registry contained 12,734 patients with VA ECMO (from years 2010 to 2019), of which 26.7% were upgraded with mechanical unloading device—IABP (in 82.9%) or Impella (in 17.1%). Patients who were finally treated with VA ECMO + IABP/ECPELLA were, before VA ECMO cannulation, in more serious condition than those who did not require LV unloading. The LV-unloaded patients required >2 vasopressors more frequently (41.7% vs. 27.2%) and had respiratory (21.1% vs. 15.9%), renal (24.6% vs. 15.8%), or liver failure (4.4% vs. 3.1%)  .A large meta-analysis by Russo et al. (2019) included 3997 patients, of which 42% underwent LV unloading on VA ECMO. The mortality in the group of patients with LV unloading was again significantly lower (54%) in comparison with the group of patients with VA ECMO only (65%). Surprisingly, in this research, 91.7% of cases were unloaded with IABP vs. 5.5% with Impella . Despitep = 0.03), but delayed LV unloading (defined as Impella implantation >2 h after VA ECMO implantation) was not associated with better mortality outcome ; p = 0.22) [A comprehensive insight was brought into the topic by Schrage et al. (2020). This multi-center international cohort study (686 patients) confirmed the other results. The mortality of ECPELLA group subjects was 58.3%  vs. 65.7%  in ECMO-only subjects. Additionally, the analysis of subgroups was performed to explore the role of right timing of LV unloading and initiation. The data showed that early LV unloading was associated with significantly lower 30-day mortality ;  = 0.22) . Another = 0.22) . Thus, tThe ECPELLA approach seems to be a promising strategy that may bring the improvement of CS mortality rates. The series of presented trials and meta-analyses clearly showed the potential benefits of this strategy. However, the ongoing research has brought a series of new questions, such as whether Impella itself is the only right unloading modality, or any other approach to unload the LV would be beneficial in the same way. Furthermore, the discussion about the right timing of the LV unloading initiation was opened. On the other hand, ECPELLA requires additional arterial access, and its association with the increased rate in bleeding complications and hemolysis is also clearly based on the significant evidence.As already mentioned, it is clear that this kind of research is connected to multiple challenges including not only statistical and medical but also ethical and legal issues associated with designing such trials. Considering a low absolute number of patients with CS shock indicated for VA ECMO treatment, followed by a thorough selection of subjects, it is clear that a single-center trial would not be able to collect sufficient data. Thus, experienced international teams should be those who might be eligible to design and manage multi-center trials without significant mistakes in the architecture of the study.From a “bedside-clinician” point of view, understanding of VA ECMO-driven circulation pathophysiology is crucial for further hemodynamic assessment of possible LV overload. Analysis of multiple measurements, such as loss of arterial line curve pulsatility, PAC values, echocardiographic evaluation of the aortic valve remaining closed, LV dilation, and progressive hypoxemia , may lead to the decision to initiate LV unloading.


To identify the survival and prognostic factors for cardiac amyloidosis (CA) in Chinese patients.  This was a prospective cohort study of 72 patients diagnosed with CA and admitted to the PLA General Hospital between November 2017 and April 2021. Demographic, clinical, laboratory, electrocardiographic, conventional ultrasound, endocardial LS during LV systole (LV ENDO LSsys), and myocardial strain data were recorded. Survival was assessed. All-cause mortality was the endpoint. Follow-up was censored on September 30, 2021. P = 0.002), log-proBNP level , and ENDO LSsys of the LV basal level  were independent prognostic factors for CA.  The mean follow-up was 17.1 ± 12.9 months. Among the 72 patients, 39 died, 23 survived, and 10 were lost to follow-up. Mean survival for all patients was 24.7 ± 2.2 months. Mean survival was 32.7 ± 2.4 months among patients with NYHA class II, 26.6 ± 3.4 months for NYHA class III, and 5.8 ± 1.1 months for NYHA class IV. The multivariate Cox proportional hazard regression model showed that NYHA class (HR = 3.42, 95% CI: 1.36–8.65,  NYHA class, proBNP level, and ENDO LSsys of the LV basal level were independently associated with the survival of patients with CA. Cardiac amyloidosis (CA) is characterized by the deposition of amyloid plaques in the myocardial interstitium, leading to the disruption of normal cardiac structure and function and, consequently, to myocardial dysfunction and conduction abnormalities or systemic amyloidosis with cardiac involvement . CardiacVelocity vector imaging (VVI) is a quantitative two-dimensional grayscale echocardiographic modality that uses a more complex approach than the speckle-tracking method. It allows the 3-dimensional quantification of myocardial deformation in the different layers of the left ventricle (LV). Longitudinal shortening, circumferential shortening, radial thickening, LV myocardium rotation, and twist can be quantified using VVI –9. StudiIn an initial pilot study , we usedTherefore, the main objective of the present study was to identify independent factors that could influence the prognosis of Chinese patients with CA, among demographic characteristics, clinical manifestations, laboratory testing indicators, electrocardiographic features, conventional echocardiographic parameters, and LS determined using LV endocardial VVI. We also aimed to examine the survival of these patients.This was a prospective cohort study of 72 patients diagnosed with CA and admitted to the PLA General Hospital between November 2017 and April 2021. The exclusion criteria were as follows: (1) acute or previous myocardial infarction or (2) with moderate or severe aortic valve lesions. In the present study, all patients with hypertrophy and suspected CA underwent echocardiography and cardiac magnetic resonance imaging (MRI) examination to confirm the diagnosis. This study was approved by the ethics committee of the PLA General Hospital . All enrolled subjects provided a written informed consent.CA was diagnosed on the basis of the following criteria : (1) conThe following data were recorded within 2 weeks after diagnosis: demographics, clinical symptoms, results of physical examination, and laboratory data  assay; blood chemistry, i.e., creatinine (Cr), proBNP, TnT, creatine kinase (CK), and creatine kinase isoenzyme (CK-MB) assays; and 24 h urinary proteins); results of ECG , echocardiography (including thickness of the interventricular septum (IVS) and left ventricular posterior wall (LVPW), LV end-diastolic and end-systolic diameters  and volume , state of the left atrium, LV chamber size (LA and LV), LV ejection fraction (LVEF), ratio of mitral peak early diastolic flow velocity (E), mitral peak late diastolic blood flow velocity (A), E-peak deceleration time (DT), and pericardial effusion (PE)), chest radiography, and abdominal ultrasound or computed tomography; and results of bone marrow aspiration and noncardiac tissue biopsy examination. All blood cell analyses were performed using an automatic blood cell analyzer. All blood biochemistry analyses were carried out using an automated chemiluminescence system using all original reagents from the manufacturer. Urinary proteins were assessed using a BS-480 analyzer. For VVI imaging, clear apical four-chamber, two-chamber, and three-chamber views were selected for imaging. Two-dimensional dynamic grayscale images of three consecutive cardiac cycles were recorded and saved at 70–105 frames/second . Then, EThe diagnosis was the starting point of observation. All-cause mortality was the endpoint. Follow-up was censored on September 30, 2021. Survival status was monitored by the same doctors every 3 months by phone. The patients received outpatient or hospital follow-up  every 6 months. The endpoint event (death) was determined by the local police or on the basis of a death certificate provided by a hospital. Patients who could not be reached three consecutive times were considered lost to follow-up.Patients underwent standard 12-lead ECG in the supine position. ECG indicators for examination were rhythm, conduction abnormalities , low voltage in the limb leads , pseudo-Q-wave infarction , and left ventricular hypertrophy .Ultrasonic diagnostic apparatus  with a 4V1c probe was used to acquire two-dimensional echocardiographic images, Doppler images, and VVI images. The SC2000 eSie VVI software was used to process VVI images. The main observation indicators for conventional echocardiography were thickness of the interventricular septum (IVS) and left ventricular posterior wall (LVPW), LV end-diastolic and end-systolic diameters  and volume , state of the left atrium, LV chamber size (LA and LV), LV ejection fraction (LVEF), ratio of mitral peak early diastolic flow velocity (E), mitral peak late diastolic blood flow velocity (A), E-peak deceleration time (DT), and pericardial effusion (PE). Doppler imaging (TDI) was used to measure the maximum mitral annulus early myocardial diastolic velocity e′ and the E/e′ ratio.For VVI imaging, patients diagnosed with CA lay on the examination table in the left lateral position, and coordinated ECG monitoring was conducted. Clear apical four-chamber, two-chamber, and three-chamber views were selected for imaging. Two-dimensional dynamic grayscale images of three consecutive cardiac cycles were recorded and saved at 70–105 frames/second. The SC2000 eSie VVI software was used for parameter analysis. First, the analysis interface of the software was accessed, the point where the endocardium of the left ventricle was clearly exposed was selected and free-framed in the three abovementioned views, and the ventricular endocardial border was draw manually. Next, the software automatically traced the epicardial boundary, with manual adjustments when necessary . Then, EP values < 0.05 were considered statistically significant.Continuous data were presented as mean ± standard deviation, while categorical data were presented as frequencies. Survival was estimated using the Kaplan-Meier analysis. Survival comparison was performed using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model. Demographics, clinical features, imaging  and global), and laboratory findings were analyzed using univariate methods. For the latter analysis, the model had three modes: clinical features alone, clinical features + laboratory findings, and clinical features + laboratory findings + echocardiographic data. All statistical analyses were performed using SPSS 21.0 . Two-sided n = 39) and the survival group (n = 33). P > 0.05). But there were more patients with advanced NYHA class in the nonsurvival group (P < 0.001), as well as more patients with multiple involved organs (P = 0.02), higher log NT-proBNP levels (P = 0.002), and higher TnT levels (P = 0.01)  .P > 0.05), but the thickness of the interventricular septum and the left ventricular posterior wall of the nonsurvival group was significantly increased compared to that of the survival group . Meanwhile, left diastolic function parameters of E/A, E/e′, were significantly increased in the nonsurvival group than the survival group . P < 0.05).The longest follow-up was 47 months. The mean follow-up was 17.1 ± 12.9 months. Among the 72 patients, 39 died, 23 survived, and 10 were lost to follow-up. Thirty patients (70%) with AL-CA received systemic blood chemotherapy and biological treatments; of these, five patients underwent autologous bone marrow stem cell transplantation.Mean survival for all patients was 24.7 ± 2.2 months, and the median survival was 22.0 months . Mean suP < 0.001), log NT-proBNP level , TnT levels , thickness of the LVPW posterior wall , E/e′ , and ENDO LSsys of LV IVS , LV POS , LV basal level , and global ENDO LSsys  were identified as factors that may have an impact on the prognosis of patients with CA.P = 0.002), log-proBNP level , and ENDO LSsys of the LV basal level  were independent prognostic factors for CA.The multivariate Cox proportional hazard regression model was subsequently used to identify independent prognostic factors for CA with three modes of analysis: clinical features alone, clinical features + laboratory findings, and clinical features + laboratory findings + echocardiographic data . As seenCA has a poor prognosis , 11–13, Systemic amyloidosis is a multisystem disease due to the deposition of amyloid substances in various organs, and its annual incidence is about 6–10 per 100 million people . AL-CA, In the present study, the mean survival of the overall cohort was 24.7 ± 2.2 months, and the median survival was 22.0 months. The survival in the present study was longer than in previously published reports , 15. ThiSince the prognosis of CA patients is generally poor, it is important to investigate the factors that affect the prognosis of CA in order to achieve early recognition of the disease progression. Several studies , 16–18 hThe present study showed that ENDO LSsys at IVS, POS, and ASE walls and basal level and of global LV were associated with CA prognosis, suggesting that the ENDO LSsys, as a parameter of myocardial motion mechanics, not only reflects changes in deformation ability of the heart of CA patients but also plays a role in the prognosis of CA. The multivariate analysis showed that the NYHA class, proBNP level, and ENDO LSsys were independent factors that could predict the prognosis of CA. NYHA cardiac function class has been identified as an independent predictive factor of CA prognosis in several studies, both domestic and international , 19, andThis study has some limitations. Although the number of observed indicators was quite high, the sample size of this study was small, and the follow-up was limited. In future studies, we will include a larger sample and increase the follow-up time, whereby we may be able to identify more accurate and reliable factors that could predict CA prognosis. In addition, we treated 10 patients who were lost to follow-up as living patients, which may affect the results of this study.The present study strongly suggests that NYHA class, proBNP level, and ENDO LSsys of the basal level of LV were independently associated with survival of patients with CA. Therefore, these parameters can be used clinically to predict the prognosis of CA patients and may form the basis for an effective treatment method for these patients.


The demand for durable left ventricular assist devices (LVADs) has been increasing worldwide in tandem with the rising population of advanced heart failure patients. Especially in cases of destination therapy, instead of bridges to transplantation, LVADs require a lifelong commitment. With the increase in follow-up periods after implantation and given the lack of donor hearts, the need for managing concomitant tachyarrhythmias has arisen. Atrial and ventricular arrhythmias are documented in approximately 20% to 50% of LVAD recipients during long-term device support, according to previous registries. Atrial arrhythmias, primarily atrial fibrillation, generally exhibit good hemodynamic tolerance; therefore, catheter ablation cannot be easily recommended due to the risk of a residual iatrogenic atrial septal defect that may lead to a right-to-left shunt under durable LVAD supports. The clinical impacts of ventricular arrhythmias, mainly ventricular tachycardia, may vary depending on the time periods following the index implantation. Early occurrence after the operation affects the hospitalization period and mortality; however, the late onset of ventricular tachycardia causes varying prognostic impacts on a case-by-case basis. In cases of hemodynamic instability, catheter ablation utilizing a trans-septal approach is necessary to stabilize hemodynamics. Nonetheless, in some cases originating from the intramural region or the epicardium, procedural failure may occur with the endocardial ablation. Specialized complications associated with the state of LVAD support should be carefully considered when conducting procedures. In LVAD patients, electrophysiologists, circulatory support specialists, and surgeons should collaborate as an integrated team to address the multifaceted issues related to arrhythmia management. Durable left ventricular assist devices (LVADs) represent potent instruments for enhancing both survival and quality of life for patients afflicted with end-stage heart failure, and the rate of LVAD implantations has increased ,2. TachyThe current LVADs are electrically actuated continuous-flow pumps represented by the following two devices: the HVAD  and the HeartMate 3 . In patients with a continuous-flow LVAD, in addition to the underlying myocardial dysfunction or scar, the absence of a physiological pulse results in heightened sympathetic nerve activity attributed to the distortion of arterial baroreceptors . This maAnti-arrhythmic drugs are recognized as one of the treatment options for tachyarrhythmias. Nevertheless, their negative inotropic and chronotropic effects can pose challenges for heart failure patients with reduced systolic function. Consequently, amiodarone spontaneously emerges as the sole choice for LVAD recipients. However, concerns have emerged regarding the use of amiodarone ,10. TherIn patients prior to LVAD implantation, the incidence of atrial arrhythmias, with the majority being atrial fibrillation (AF), has been reported to range from 21% to 54% in the literature . AdditioHowever, LVAD therapy originally requires warfarin administration to prevent pump thrombosis and ultimately reduce the load on the left ventricle, irrespective of the presence of AF, potentially mitigating the negative impact of AF. Nevertheless, several observational studies have reported that preoperative AF, particularly the persistent type, is associated with increased mortality, a higher degree of functional tricuspid regurgitation, a higher incidence of new-onset ventricular arrhythmias, and a greater occurrence of late right heart failure when compared to individuals without AF ,14,15,16Concomitant left atrial appendage occlusion in patients receiving LVAD implantation may have the potential to reduce adverse events such as stroke or thromboembolisms . On the However, in some cases, hemodynamic instability occurs due to AF, leading to the absence of the atrial kick . If a raVentricular tachyarrhythmias are common for LVAD recipients, ranging from 20% to 50% depending on the underlying type of cardiomyopathy, existence of preoperative ventricular arrhythmias, and length of follow-up ,24,25,26Ventricular arrhythmias occur more frequently in the early postoperative period; therefore, ventricular tachyarrhythmias following LVAD implantation are typically categorized into two phases: early onset within 30 days of surgery and late-onset thereafter . Early vEarly ventricular arrhythmias have emerged as a significant risk factor for mortality, particularly in patients undergoing destination therapy or experiencing electrical storms of ventricular arrhythmias ,35,36. IHowever, the clinical impact of late-onset ventricular arrhythmias is still a matter of debate. An observational multicenter registry revealed no statistically significant prognostic discrepancy in the presence of late-onset ventricular arrhythmias when comparing groups with and without such arrhythmias . On the One important point to remember is that ventricular arrhythmias are also associated with right ventricular failure, which, in turn, is linked to mortality ,42. AortCatheter ablation is widely recognized as a definitive treatment tool for tachyarrhythmias. Nevertheless, this technique presents particular challenges that elevate the risk of complications in LVAD support situations. To commence, in order to secure the success of procedures, the three-dimensional mapping systems that employ magnetic field sensors are of paramount importance. However, the issue of electromagnetic interference between three-dimensional mapping systems and LVAD motors is a significant concern in the context of precise electrophysiological studies. The previous devices, such as HVAD and HeartMate II, are less likely to interfere with magnet-based mapping systems. Nevertheless, there were some cases that exhibited limitations in visualizing the catheter’s position or performing electrophysiological mapping, particularly in the inferior or septal apical segments around the cannula and facing the turbine  46]. He. He46]. In patients with continuous-flow LVADs, it is common practice to employ invasive hemodynamic monitoring during the ablation procedures due to the inability to measure cuff pressure noninvasively. In the context of left heart access techniques, it is notable that the majority of ventricular tachyarrhythmias observed in LVAD recipients have their origin within the left ventricle. However, a trans-aortic valve approach is impractical due to the aortic transvalvular gradient, which promotes aortic valve closure . A tempoWhile LVAD recipients are typically prescribed warfarin anticoagulant therapy with a target international normalized ratio level of <3.5, intravenous heparin should be administered to achieve an activated clotting time exceeding 300 s when accessing the left atrial or ventricular endocardium . TherefoAn observational study reported an increased risk of pump thrombosis and thromboembolic events following endocardial ablation . HemolysThese procedural complications were reported to have occurred in 9.4% of ablation cases among LVAD recipients, a rate higher than that observed in patients without LVAD implantation ,55. The AF is the predominant supraventricular arrhythmia in patients with LVADs . HoweverAtrial flutter, occurring in up to 50% of patients after open-heart surgery and 15% of patients following LVAD implantation, represents another significant form of atrial tachyarrhythmia ,58. SimiIn cases of recurrent VT presenting with complaints of palpitations or hemodynamic compromise manifesting as low-flow alerts, VT ablation should be given due consideration . Over 90The short-term procedural success rate for VT ablation has been reported to be approximately 80% . The majThe activation map within the left ventricle revealed centrifugal propagation originating from the lateral wall, with the white area indicating the earliest activation site. This arrhythmia could not be terminated by radiofrequency delivery due to the speculated origin within the intramural layer or epicardium. The surface electrocardiogram of the present tachycardia is shown in VF is generally a formidable challenge to address via catheter ablation. Nonetheless, directing efforts towards addressing initiated ventricular premature contractions may prove effective in diminishing the recurrence of VF, particularly in cases of intractable electrical storms accompanied by hemodynamic compromise . It is wPatients supported with LVADs demonstrate diverse adverse events such as right ventricular failure, an increase in pulmonary vascular resistance, hematic congestion, as well as an increased burden of arrhythmias. These events are not manifested in isolation; rather, they are intricately interconnected. Effective management of these events necessitates a multifaceted approach, encompassing not only arrhythmia treatment but also adjustments in medication and optimization of LVAD speed by circulatory support specialists . In addiTachyarrhythmias originating from both the atrium and the ventricle are frequently encountered in LVAD recipients. While robust hemodynamic support typically mitigates the prognostic impact of tachyarrhythmias, some cases still result in a decline in their quality of life or hemodynamic compromise, necessitating invasive catheter ablation. Due to the distinctive hemodynamics and patient vulnerability inherent in LVAD recipients, catheter ablation-related complications exhibit a wide spectrum of diversity, rendering them more susceptible to occurrence compared to patients without LVAD implantation. The population of LVAD-supported patients is expected to increase, serving as both a bridge to transplant therapy and a destination therapy. To address the intricate and refractory arrhythmia issues in LVAD patients, not only electrophysiologists but also circulatory support specialists and surgeons should collaborate with each other. There is also a pressing need for further accumulation of knowledge concerning the impacts of catheter ablation and the associated procedural complications see .The prognostic impacts of arrhythmias differ between atrial and ventricular arrhythmias. Several issues related to catheter ablation should be managed by specialists in electrophysiology, circulatory support, and surgery.


Dear Editor,A range of disorders impacting the cardiovascular system, which includes the heart and blood vessels, are referred to as cardiovascular diseases (CVDs). This mainly includes coronary artery disease, coronary heart disease, cerebrovascular disease, peripheral artery disease, and aortic atherosclerosis2.5) and particulate matter measuring 10 µm in diameter or less (PM10) concentration are used to determine AP. As per WHO 2021 Air Quality guidelines the highest recommended average annual emission level for PM2.5 was 5 μg/m3 and for PM10 was 15 μg/m3et al.10 was associated with an increased risk of death due to CVD. Furthermore, a study was done by Pope and colleagues, showing a statistical association between PM2.5 and overall cardiovascular mortality. The risk of myocardial infarction, ischemic heart disease, arrhythmia, heart failure, or cardiac arrest death was increased in polluted areas2.5 concentration in 2021, by the WHO guidelines. 2021 average PM2.5 concentration in Pakistan is 13.4 times the WHO annual air quality guidelinesIt has been shown in a few studies that AP increases the chance of developing CVDs such as myocardial infarction, ischemic heart disease, cardiac arrhythmia, heart failure, or cardiac arrestAccording to WHO data from 2016, about 19% of all deaths in Pakistan were due to heart diseases. However, in only 3 years, a 29% increase occurred in deaths caused by CVDs2.5 concentration and take measures to reduce such as but not limited to, restricting open burning of waste and regulations to mitigate emissions from vehicles and factories. The government should make policies to reduce the use of fossil fuels for energy and replace it with increased construction and use of solar power and hydropower plants. Pakistan needs to protect its vulnerable population from AP-associated CVDs, otherwise, the death rate through CVDs could increase from the already appalling 29% in the near future.CVD patients need multifactorial interventions, especially more intensive measures to modify individual cardiovascular risk factors with diet, drugs, exercise, weight management, complete smoking cessation, and avoidance of secondhand smoke, or combinations thereofMultiple studies have associated air pollution (AP) with an increased risk of CVDs and CVD-associated mortality.The mortality rate in Pakistan has seen a 29% increase over three years due to CVDs.This article calls out the Government and respective authorities to take precautionary measures as constantly striking AP may appall the CVD associated mortality in the near future.Not applicable.None.S.T.R. and A.I. conceived the idea. S.K., U.N., H.u.H., I.U., and M.S.A. collected the data. S.T.R. and M.S.A. analyzed and interpreted the data. I.U. and S.T.R. did write up of the manuscript. M.S.A. reviewed and revised the manuscript for intellectual content critically. All authors approved the final version of the manuscript.The authors declare that they have no financial conflict of interest with regard to the content of this report.None.Muhammad Sohaib Asghar.Externally peer reviewed, not commissioned.


Persistent pulmonary hypertension of the newborn (PPHN) is usually considered a consequence of impaired pulmonary circulation. However, little is known regarding the role of cardiac dysfunction in PPHN. In this study, we hypothesized that the tolerance for pulmonary hypertension in newborn infants depends on the biventricular function. The aim of this study is to evaluate biventricular cardiac performance by using Tissue Doppler Imaging (TDI) in an healthy newborn infants with asymptomatic pulmonary hypertension and in newborn infants with PPHN.Right and left cardiac function were investigated using conventional imaging and TDI in 10 newborn infants with PPHN (“PPHN”) and 10 asymptomatic healthy newborn infants (“asymptomatic PH”).p < 0.05). Left ventricular (LV) function was normal in both groups with a systolic velocity (S'LV) at the LV free wall groups .Systolic pulmonary artery pressure (PAP) as assessed by TDI and the mean systolic velocity of the right ventricular (RV) free wall were similar in both groups. The isovolumic relaxation time of the right ventricle at the tricuspid annulus was significantly longer in the “PPHN” than in the “asymptomatic PH” group (53 ± 14 ms vs. 14 ± 4 ms, respectively; The present results suggest that high PAP with or without respiratory failure is not associated with altered right systolic ventricular function and does not affect LV function in newborn infants. PPHN is characterized by a marked right diastolic ventricular dysfunction. These data suggest that the hypoxic respiratory failure in PPHN results, at least in part, from diastolic RV dysfunction and right to left shunting across the foramen ovale. We propose that the severity of the respiratory failure is more related to the RV diastolic dysfunction than the pulmonary artery pressure. PhysiolMost of the studies regarding PPHN pathogenesis have focused on the primary role of pulmonary circulation . AbnormaDue to a high degree of interdependence between the right and left ventricles owing to the presence of common structures (the interventricular septum and the inextensible pericardium), changes in right ventricle size and geometry may alter LV function , 7. ThisTissue Doppler Imaging (TDI) is used to evaluate the right cardiac performance. Myocardial TDI is a tool which allows a quantitative evaluation of the cardiac wall's movements by measurement of the intramyocardic velocities in real time. Compared to conventional Doppler techniques, TDI is an important advance in the assessment of cardiac function given its relative pre- and post-load independence and reproducibility . WhereasWe hypothesize that the tolerance of pulmonary hypertension in newborn infants is dependent on cardiac function. In order to investigate this hypothesis, we conducted a comparative analysis of cardiac function between newborn infants with asymptomatic pulmonary hypertension and those with pulmonary hypertension associated with severe respiratory failure.2.2.1.This prospective observational study was conducted at the Nursery and Neonatal Intensive Care Units of Lille University Hospital, France. We included newborn infants with a gestational age >36 weeks and PPHN (group “PPHN”) as defined by severe respiratory failure . Asymptomatic newly born infants with no respiratory failure were included in the “asymptomatic PH” group. In both groups, newborn infants had a postnatal age of <2 h. The exclusion criteria were congenital cardiopathy, gestational age <36 weeks, use of inotropic drugs, and hypovolemia. Informed consent was obtained from the parents. This study was approved by the National Commission on Informatics and Liberty.2.2.All examination procedures were performed to provide a comprehensive echocardiographic examination for assessing RV and LV systolic and diastolic function using several indexes. Tissue Doppler Imaging (TDI) was performed in the supine position using an ultrasound machine . One investigator performed all the TDI procedures. We used TDI to evaluate right cardiac performance. Myocardial TDI is a tool that allows the quantitative evaluation of cardiac wall movements via measurement of intramyocardial velocities in real time. Whereas conventional Doppler techniques focus on the low-intensity, high-velocity echoes of blood flow, TDI measures the high-intensity, low-velocity echoes of the myocardium. There is a physical difference between the signal returning from moving blood and cardiac tissue motion because the velocity in the hydraulic part (blood) is higher than that in the mechanic part (tissue) . TDI has–Left ventricular shortening fraction (LVSF) from a parasternal long-axis view .–ΔP = 4V2|), which is a noninvasive method supported by the literature  and peak late diastolic velocity (A).–Systolic velocity (S'), early diastolic velocity (E'), and late diastolic velocity (A') by TDI at the RV free wall  and at the LV free wall  by TDI pulsed spectral imaging of a sample volume length of 2–5 mm is placed within the myocardial wall of interest, interrogating the wall motion parallel to the cursor orientation. Images of the right and left ventricles were chosen to minimize the angle of incidence between the scanlines and the motion of the base of the heart. Filters were set to exclude high-frequency signals, and gains were set to obtain clear tissue signals with minimal background noise.–Isovolumic relaxation time of the right ventricle . The IVRT is the time between the closure of the pulmonary valve and the opening of the tricuspid valve. During this phase, the ventricle is a closed cavity whose volume does not change while the pressure generated during the systole decreases exponentially.–Inferior vena cava diameter (mm) using the low subcostal view;–To calculate the E/E' ratio, off-line analyses included measurements of E and E' for both ventricles.Doppler measurements represent the average of three beats. Special care was taken to prevent angulation between the ultrasound beam and blood flow. The following Doppler parameters  were measured:2.3.P values < 0.05 were considered statistically significant.The results are presented as means ± standard error of the mean. The data were analyzed using factorial analysis of variance. Intergroup differences were analyzed using the Kruskal–Wallis test . The Mann–Whitney test  and paired Wilcoxon rank test  were used to compare groups. 3.p = 0.08). PPHN-related diseases are shown in p = 0.64). The mean DA diameter was equal between the two groups .Twenty newborn infants were included in the study (10 in each group). The mean gestational age was 39 ± 1 weeks in the “asymptomatic PH” group and 38 ± 2 weeks in the “PPHN” group (p = 0.6). The mean birth weights were similar in each group . No statistically significant difference in the mean diameters of the inferior vena cava was found between the two groups (p = 0.42). No significant difference in systolic velocity (S’RV), early diastolic velocity (E’RV), or late diastolic velocity (A’RV) was found by TDI at the RV free wall, and E/E’RV did not differ significantly between the two groups (o groups . No diffo groups .3.2.p = 0.12) and  (p = 0.39), EM , and E/E'LV ; Systolic velocity (S’LV) at the LV free wall and the LVSF were similar in the two groups  . In addi4.In this study, we investigated the role of cardiac function in pulmonary hypertension tolerance in newborn infants. We evaluated diastolic and systolic ventricular function using spectral TDI in newborn infants with pulmonary hypertension with and without associated severe respiratory failure. Whereas PAP was similar, the RV isovolumic relaxation time was longer in newborn infants with respiratory failure. These results suggest that respiratory failure in pulmonary hypertension of the newborn is associated with RV diastolic dysfunction..Inadequate visualization of the RV free wall precludes accurate measurements of changes in the RV fractional area and ejection fraction  is proportional to right atrial pressure . The E'RThe mechanism of PPHN-induced diastolic RV dysfunction is presently unknown. Previous studies have reported that PPHN is associated with increased pro-inflammatory cytokines and oxidative stress . Pro-infPrevious studies in adults or newborns with congenital diaphragmatic hernias have shown that RV dysfunction may impair LV function . It can In our study, we assess pulmonary arterial pressures using the pressure gradient across the patent ductus arteriosus (PDA), a method that has been validated in the literature , 18. HowOur study has several limitations that should be acknowledged. Firstly, the sample size was small, which may limit the generalizability of our findings. Secondly, all measurements were performed by a single observer, introducing the potential for observer bias. It would have been valuable to have a second investigator independently perform the measurements and report the inter-observer variability. Furthermore, the absence of direct hemodynamic data, such as cardiac catheterization, is notable. However, given the invasiveness of this technique, it was not feasible to perform it in our vulnerable population. Instead, we relied on non-invasive measures to assess cardiac function. Another potential limitation is the possibility of selection bias in this small, non-randomized study. Clinical decisions were made by a multidisciplinary team throughout the day to ensure standardized patient care and minimize bias. However, it is important to acknowledge that the possibility of selection bias cannot be completely eliminated. It would have been interesting to include LV IVRT in the TDI analysis of the left ventricle, and this warrants further studies. In summary, while our study provides valuable insights, the limitations regarding sample size, single observer measurements, absence of direct hemodynamic data, and potential selection bias should be taken into consideration when interpreting the results.5.Taken together, we found that, compared with asymptomatic pulmonary hypertension, PPHN is characterized by marked right diastolic ventricular dysfunction, whereas systolic function is preserved. The impaired RV diastolic function causes a decrease in RV compliance. Thus, the hypoxic respiratory failure in PPHN results, at least in part, from the diastolic RV dysfunction-induced increase in right-to-left shunting across the foramen ovale. We propose that the severity of the respiratory failure is more related to the RV diastolic dysfunction than the pulmonary artery pressure.


Cardiovascular magnetic resonance (CMR) comprehensively assesses aortic stiffness and myocardial ischemia in a single examination. Aortic stiffness represents a subclinical marker of cardiovascular risk in the general population, including patients with diabetes mellitus. However, there is no prognostic data regarding aortic stiffness in patients with diabetes mellitus undergoing stress perfusion CMR.Consecutive patients with diabetes mellitus with suspected myocardial ischemia referred for adenosine stress perfusion CMR with aortic pulse wave velocity (PWV) during 2010–2013 were studied. The primary outcome was major adverse cardiovascular events (MACE), defined as the composite of cardiac mortality, nonfatal myocardial infarction (MI), hospitalization for heart failure, coronary revascularization (> 90 days post-CMR), and ischemic stroke. The secondary outcome was hard cardiac events, defined as the composite of cardiac mortality and nonfatal MI.A total of 424 patients (median follow-up 7.2 years) were included. The mean PWV was 12.16 ± 6.28 m/s. MACE and hard cardiac events occurred in 26.8% and 9.4% of patients, respectively. Patients with elevated PWV (> 12.16 m/s) had a significantly higher incidence of MACE  and hard cardiac events  compared to those with non-elevated PWV. Multivariable analysis demonstrated that PWV independently predicts MACE (p = 0.003) and hard cardiac events (p = 0.01). Addition of PWV provided incremental prognostic value beyond clinical data, left ventricular mass index, myocardial ischemia, and late gadolinium enhancement in predicting MACE  and hard cardiac events .Aortic stiffness measured by CMR independently predicts MACE and hard cardiac events and confers significant incremental prognostic value in patients with diabetes mellitus with suspected myocardial ischemia. Aortic stiffness measurement could potentially be considered as part of a stress perfusion CMR protocol to enhance risk prediction in patients with diabetes mellitus.The online version contains supplementary material available at 10.1186/s12872-023-03532-0. Patients with diabetes mellitus are at an increased risk of developing coronary artery disease (CAD) and experiencing future cardiovascular events. Despite significant advances in diabetes management and care, diabetes remains associated with considerable mortality, with the primary cause of cardiovascular death being CAD . AccordiAortic stiffness is a subclinical marker of cardiovascular risk in both general population and in patients with diabetes mellitus , 4. MeasFurthermore, and importantly, CMR can assess PWV and perform a stress perfusion test in a single examination. We recently demonstrated the association between aortic stiffness and myocardial ischemia, as well as the prognostic value of aortic stiffness using CMR , 10. SwoWe retrospectively enrolled consecutive patients with diabetes mellitus referred for adenosine stress perfusion CMR with PWV to evaluate suspected myocardial ischemia. The study was conducted at the Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, from 2010 to 2013. At our institution, the assessment of aortic stiffness using PWV is a standard component of our comprehensive CMR protocol for CAD evaluation. All patients were aged > 18 years, and the diagnosis of diabetes mellitus was established according to the current American Diabetes Association guidelines . PatientDetailed medical history and medications were collected on the day of the CMR study. Diagnosis of hypertension, hyperlipidemia, CAD, and ischemic stroke was defined according to recent guidelines –16. ElecThis study was approved by Siriraj Institutional Review Board (SIRB) (COA no. Si 782/2016), Faculty of Medicine Siriraj Hospital, Mahidol University. The need for consent was waived by the board due to its retrospective nature and as all personal identifying information was obliterated. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki.CMR was performed to assess cardiac function, stress perfusion, LGE, and PWV using a 1.5 T Philips Achieva XR Scanner . A cardiac functional study was performed using images acquired via a standard retrospective ECG-gated cine balanced steady-state free precession (SSFP) sequence in multiple short- and long-axis views. The image parameters were spatial resolution 1.5 × 1.5 × 8.0 mm, 10–12 slices, gap 0 mm, sensitivity encoding factor 2, repetition times (TR) 3.3 and 2.7 ms, echo times (TE) 1.6 and 1.3 ms, field of view (FOV) 270 × 320 mm, and flip angle 60 degrees.The myocardial first-pass perfusion study was performed by injection of 0.05 mmol/kg of gadolinium contrast agent  at 4 ml/s immediately after a 4-minute infusion of 140 mcg/kg/min of adenosine. At least three short-axis slices of basal, mid, and apical left ventricular (LV) levels were acquired using an ECG-triggered, SSFP, inversion-recovery, single-shot, turbo gradient-echo sequence. The image parameters were TR 2.6 ms, TE 1.32 ms, FOV 270 × 320 mm, and flip angle 50 degrees.PWV images were acquired during the waiting period between the stress and LGE imaging and determined with the free-breathing, velocity-encoded CMR (VE-CMR) technique as through-plane flow in the mid-ascending and mid-descending thoracic aorta at the level of the pulmonary trunk. The imaging parameters were retrospective ECG trigger, TR 5.3 ms, TE 3.1 ms, flip angle 12 degrees, FOV 250 × 210 mm, slide thickness 8 mm, matrix 2.0 × 2.0 mm, reconstructed spatial resolution 1.12 × 1.12 mm, temporal resolution 10–20 ms, and velocity encoding 170 cm/s [LGE images were acquired approximately 10 min after administration of an additional bolus of gadolinium  via a 3D segmented gradient-echo inversion-recovery sequence. The images were acquired in multiple short- and long-axis views similar to the functional images. The parameters for the LGE study were TR 4.1 ms, TE 1.25 ms, flip angle 15 degrees, FOV 303 × 384 mm, matrix 240 × 256, in-plane resolution 1.26 × 1.5 mm, and 1.5 sensitivity-encoding factor.Standard LV volumes, mass, and ejection fraction (EF) were quantitatively measured from the stack of short-axis SSFP cine images . The perThe PWV analysis was performed using EasyVision 5.2 , separate from the functional, perfusion, and LGE studies. .Where Δ x reflects the length of the aortic path between the mid-ascending and mid-descending thoracic aorta, and Δ T represents the time delay between the arrival of the foot of the pulse wave at these two corresponding levels. Our research group reported excellent intraobserver and interobserver agreement for PWV measurement .Follow-up data were collected from clinical visits, medical records, or contact with the patient’s physician. Event adjudication was blinded to clinical and CMR data. The prespecified primary outcome was major adverse cardiovascular events (MACE), which was defined as the composite of cardiac mortality, nonfatal myocardial infarction (MI), hospitalized for heart failure, coronary revascularization, and ischemic stroke. The secondary outcome was hard cardiac events, which was defined as the composite of cardiac mortality and nonfatal MI. Cardiac mortality was defined as all deaths in the setting of CAD, congestive heart failure, and sudden cardiac death . MI was Statistical analysis was performed using SPSS Statistics version 22.0 . Continuous data are presented as mean ± SD or median and interquartile range (IQR), as appropriate. Categorical variables were presented as absolute numbers and percentages. Continuous data were compared using the two sample t-test or the Mann–Whitney U test. Categorical data were compared using χ2 tests or Fisher’s exact tests as appropriate. Elevated and non-elevated PWV were defined as values above and below the mean of the entire cohort, respectively. To analyze the predictors of elevated PWV, we conducted a binary logistic regression analysis to evaluate univariable predictors based on baseline characteristics and CMR parameters. Variables with a p-value < 0.05 in the univariable analysis were subsequently included in the multivariable analysis. The Kaplan-Meier method was utilized to estimate composite outcomes for MACE and hard cardiac events in both patients with elevated and non-elevated PWV, as well as among PWV tertiles. These estimates were then compared using the log-rank test. To analyze the predictors of MACE and hard cardiac events, a Cox regression analysis was performed to assess univariable predictors from baseline characteristics and CMR parameters. Variables with a p-value < 0.05 in the univariable analysis were subsequently included in the multivariable analysis. To evaluate the incremental prognostic values of predictors for MACE and hard cardiac events, global chi-square values were calculated after adding predictors in the following order: clinical variables only, and then clinical + CMR variables. The clinical and CMR variables were derived from factors previously identified as independent predictors for MACE and hard cardiac events. Patients were subsequently divided into four groups based on the presence or absence of myocardial ischemia and elevated or non-elevated PWV. Cox regression analyses were employed to assess the relationship between the four patient groups: negative ischemia-non-elevated PWV, positive ischemia-non-elevated PWV, negative ischemia-elevated PWV, and positive ischemia-elevated PWV, and their associated outcomes. The Bonferroni-Holm method was applied to account for multiple pairwise comparisons. Finally, Cox regression analysis for MACE was performed in patients with elevated and non-elevated PWV across ten prespecified subgroups: female and male, above and below the mean age, above and below the mean body mass index (BMI), above and below the mean HbA1c, and with and without known CAD. All statistical tests were two tailed and p < 0.05 was regarded as significant.A total of 431 patients with diabetes mellitus and suspected myocardial ischemia completed CMR protocol. Four patients were excluded due to having an aortic aneurysm, and three patients were excluded due to a loss of follow-up data. Ultimately, 424 patients were included in the final analysis , MACE occurred in 114 patients (26.8%), including 40 hard cardiac events (9.4%). Clinical events in the study cohort are detailed in Table ications , 25 – thThe results of multivariable Cox survival analyses for MACE Table  and hardThe incremental prognostic value resulting from the inclusion of PWV in the predictive algorithm for MACE and hard cardiac events is presented in Table For this analysis, we divided patients into 4 groups, as follows: group 1 – non-elevated PWV and no myocardial ischemia; group 2 – elevated PWV and no myocardial ischemia; group 3 – non-elevated PWV and presence of myocardial ischemia; and group 4 – elevated PWV and presence of myocardial ischemia. The results of our analysis revealed that compared to patients with non-elevated PWV and no myocardial ischemia (group 1), patients with elevated PWV only or the presence of myocardial ischemia only (group 2 or 3) exhibited significantly higher rates of MACE  and hard cardiac events . Patients with elevated PWV and presence of myocardial ischemia (group 4) had over six times the rates of MACE  and hard cardiac events  compared to those with non-elevated PWV and no myocardial ischemia (group 1)  . Our resThis study has some mentionable limitations. First, the retrospective design of this study rendered it vulnerable to missing or incomplete data and to certain biases. For example, we were not able to include duration of diabetes mellitus in our analysis since this data was not consistently available. Secondly, we divided the group of patients using the mean PWV instead of the more common approach of utilizing the median. However, our data revealed that the mean and median PWV values were relatively close , and the main findings appear to remain unchanged. Third, although our multivariable regression models were adjusted for multiple covariates, there may be other confounding factors that influence the relationship between PWV and the incidence of cardiovascular events. Fourth, this study included Asian patients with a mean age of 70 years, so the generalizability of our findings to younger patients and to patients of other races should be performed with caution. Fourth and finally, the fact that we used the mean PWV as the cut-off value may make translating our findings into clinical practice challenging. However, since there is no optimal cut-off value for PWV in patients with diabetes mellitus, further study is warranted to identify a cut-off or cut-offs appropriate to this specific clinical setting.In conclusion, aortic stiffness by CMR independently predicts MACE and hard cardiac events and confers significant incremental prognostic value in patients with diabetes mellitus with suspected myocardial ischemia. Aortic stiffness measurement could potentially be considered as part of a stress perfusion CMR protocol to enhance risk prediction in patients with diabetes mellitus.Below is the link to the electronic supplementary material.Supplementary Material 1


Use of pacemakers has increased in recent years, and they have become the premier treatment option for several arrhythmias. However, they are not without risk; this case report aims to show the importance of follow‐up and adherence to guidelines, and methods to diagnose a life‐threatening complication. Four‐chamber view TEE showing pacemaker ventricular lead crossing the atrial septum and going down through the mitral valve (left). Modified 3‐chamber view showing ventricular lead going through mitral valve and inserting into lateral wall of left ventricle (right).  An aging population, increasing prevalence of cardiovascular disease, advances in device therapy, and introduction of implantable heart rate‐rhythm monitoring devices have resulted in an exponential gross in therapeutic cardiac device implantation worldwide. More than 300,000 pacemakers are inserted every year in the United States alone.Despite the multiple clinical scenarios in which permanent pacing is considered, most management decisions regarding permanent pacemaker implantation are driven by the association of symptoms with bradycardia. Other common indications include sick sinus syndrome (SSS), high‐grade atrioventricular block, and tachycardia‐bradycardia syndrome. It is not uncommon that pacemaker therapy is considered for the treatment of chronotropic incompetence, but it is rarely considered in patients with cardio‐inhibitory neurocardiogenic dysfunction.Permanent transvenous pacing system leads are guided through the left subclavian, cephalic, or axillary veins and eventually screwed into place in the right ventricle.We are presenting an extremely rare case of a 53‐year‐old man with an old, neglected, and misplaced right ventricular (RV) pacemaker lead, caused by a series of unfortunate events involving lack of follow‐up and neglect of the recommended guidelines before, during, and after device implantation.2A 53‐year‐old man with a history of coronary artery disease, hypertension, hyperlipidemia, and SSS presented to the emergency room for evaluation of dizziness and diaphoresis.The patient had a history of pacemaker implantation at 26 years old after a motor vehicle accident presumably secondary to dizziness and SSS. After implantation, the patient was unable to follow up with a cardiologist or primary care provider for 27 years. He claims this is because he works as a truck driver and never settled in one place. He has no insurance and usually seeks medical advice only when he has an acute illness. He never established care with a primary care provider or a cardiologist.In the emergency room, a point‐of‐care ultrasound revealed normal ejection fraction and wall motion, as well as sinus bradycardia at rest. No images of the ultrasound were recorded, and thus, no comment on the position of the pacemaker leads was made. An AP and lateral chest X‐ray were also obtained; despite showing the ventricular lead taking a sharp turn and crossing into the left chamber of the heart in the AP view Figure , the latA chest CT without contrast clearly showed the RV lead crossing the interatrial septum, crossing the mitral valve, and finally inserting into the left ventricle Figure . Again, Because of his dizziness and resting sinus bradycardia, pacemaker interrogation was attempted, but unfortunately was unsuccessful due to dead pacemaker battery. Because of his significant orthostatic dizziness and persistent sinus bradycardia in the low 50s bpm at rest, along with suboptimal heart rate response in mild‐to‐moderate activities, we discussed replacing the patient's pacemaker battery. No formal exercise stress test was done to document chronotropic incompetence.Patient underwent a pacemaker generator change and his baseline pacing rate was set at 70 bpm. He was atrial paced most of the time and, per intra‐operative testing, both atrial and ventricular leads were electrically intact. Unfortunately, neither the operator nor the pacemaker representative noted that the pattern of the ventricular pacing lead during testing had a right bundle branch block (RBBB) pattern.A week later, the pacemaker pocket was found to be infected with Klebsiella organism. The decision was made to remove the pacemaker generator. A transesophageal echo (TEE) was subsequently performed in preparation for removal of the long‐neglected leads. Imaging showed the ventricular pacemaker lead crossing through a patent foramen ovale into the left atrium, through the mitral valve, and inserting into the lateral wall of the left ventricle Figure . The TEEA sternotomy was performed. The ventricular lead was inserted into the lateral wall of the left ventricle, while the atrial lead was properly positioned in the right atrium. Both leads were surgically removed. Despite extraction, mitral valve regurgitation was persistent Figure . The mitAfter pacemaker extraction, an EP study was performed to determine eligibility for another pacemaker insertion. However, studies showed normal sinus node function , normal AV node function (AH 95 ms), and mildly prolonged HV interval (65 ms). There is no evidence of dual AV node physiology or accessory pathway. VA conduction was present. The decision was thus made to not implant another pacemaker. The patient is in general good health post‐operatively with no further dizziness or lightheadedness, and no chronotropic incompetence.3Pacemaker or ICD implantation is one of the most common cardiac interventions utilized today. They are used to treat cardiac arrythmia, including bradycardia and tachycardia. As such, indications for pacemaker implantation are numerous. ICD and pacemakers are most used to treat sinus node dysfunction (SND) and atrioventricular block. They can also treat chronic bifascicular block, hypertrophic cardiomyopathy, or patients with congenital heart disease.Pacemaker implantation is a minimally invasive procedure, but still carries risks. Nearly a third of all complications are due to lead dislodgement or malposition.A misplaced ventricular lead must quickly be diagnosed to prevent adverse events, and thus, a high degree of scrutiny is required. The most important tool to recognize a lead in the LV is an ECG; on ventricular pacing, a misplaced lead will display a RBBB morphology rather than the expected left bundle branch block (LBBB).Management of a misplaced LV lead depends on symptoms and risks of intervention. Lead removal presents a risk of thromboembolic events, and so surgical removal is usually withheld from asymptomatic patients or patients in poor health. Anticoagulation therapy is currently the most popular method of treatment. However, if anticoagulation therapy is ineffective and thromboembolic complications occur, surgical intervention must be considered.4Pacemaker and ICD implantation is a useful therapy for many arrythmias, but proper review of all indications is required. Additionally, consistent follow‐up and comments on positioning of the lead is necessary, as inadvertent placement of a pacemaker or ICD into the left ventricle is a rare but under‐reported complication that carries a high risk of thromboembolic events and must be diagnosed and treated quickly. In this case, not all events should be attributed solely to patient non‐compliance. There is no clear documentation regarding why the pacemaker was indicated, and the malpositioned left ventricular lead should have been recognized early, likely before the patient was discharged from the hospital after implantation. There are various methods useful in recognizing such a complication, including ECG, AP and lateral chest X‐rays, TEEs, or CT scans.Abdelrahman Osman: Writing – original draft. Ali Ahmad: Conceptualization; data curation; formal analysis.No funding source supported this study.The authors declare no conflicts of interest.Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.


Myocardial work acquired by echocardiography has emerged as a novel method to evaluate myocardial function. We investigated global and segmental myocardial work in hypertension (HT) among patients with different patterns of left ventricular (LV) geometry in order to analyze the contribution of segmental myocardial work to global myocardial work.P < 0.001). Global MWI (GWI) and global MCW (GCW) did not change across the different LV remodeling groups. Global MWW (GWW) increased and global MWE (GWE) decreased in both CH and EH group (P < 0.001). The LS of basal and middle regions reduced gradually in all HT subgroups, while apical LS decreased only in the CH and EH groups (P < 0.001). Basal MWI and MCW decreased in the CH and EH groups . Apical MWI and MCW increased in the NG and CR groups , with a decreasing trend in the CH and EH groups. All segmental MWW elevated and MWE reduced significantly in the CH and EH groups (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated a significant association between left atrial volume index (LAVI), GLS, GWE and LV hypertrophy. At the receiver operating characteristic (ROC) analysis, optimal cutoff values of GLS, Apical LS, GWE and Apical MWE discriminating LV hypertrophy were 0.9072, 0.8049, 0.8325 and 0.7414, respectively.One hundred twenty-five patients with HT were divided into 4 groups: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH) and eccentric hypertrophy (EH). Longitudinal strain (LS) and the following indices were obtained by echocardiography: myocardial work index (MWI), myocardial constructive work (MCW), myocardial wasted work (MWW), and myocardial work efficiency (MWE). The global longitudinal strain (GLS) decreased gradually among the groups: NG, CR, CH and EH (Apical myocardial work increases in the early stages of LV remodeling, likely as a compensatory mechanism to maintain normal global myocardial work. Segmental myocardial work analysis offers a reliable means to explore the distribution of myocardial impairment in hypertensive patients at different LV remodeling stages.The online version contains supplementary material available at 10.1186/s12947-023-00310-y. Myocardial work acquired by 2-dimensional speckle tracking echocardiography (2D-STE) is a novel parameter to evaluate left ventricular (LV) myocardial performance. It takes into account the influence of afterload and myocardial deformation on LV systolic function –3. RecenOne hundred twenty-five essential hypertensive patients  who visited the First Affiliated Hospital of Fujian Medical University from June 2021 to March 2022 were enrolled in this retrospective study. The diagnosis of essential HT was designated according to 2018 ESC/ESH Guidelines for the management of arterial HT [n = 36; Concentric remodeling (CR): normal LVMI and increased RWT, n = 20; Concentric hypertrophy (CH): increased LVMI and increased RWT, n = 24; Eccentric hypertrophy (EH): increased LVMI and normal RWT, n = 45. The classification of LV geometry and the calculation of LVMI and RWT were made according to 2015 recommendations for cardiac chamber quantification by echocardiography in adults [2  was defined as hypertrophy. RWT was calculated using the formula  / , and RWT < 0.42 was defined as normal [The enrolled hypertensive patients were divided into 4 groups according to left ventricular mass index (LVMI) and relative wall thickness (RWT): Normal geometry (NG): normal LVMI and normal RWT, n adults , where Ls normal .Comprehensive transthoracic echocardiography was performed using a GE Vivid E95 ultrasound scanner  equipped with a M5s probe (1.7–4.0 MHz). Frame rate was 50–80 frames per second. Patients were examined at rest and in the left lateral decubitus position. Electrocardiogram-triggered echocardiographic data were acquired and digitally stored in a cine-loop format for offline analysis. The following conventional parameters were measured in standard parasternal LV long axis views, apical 4-chamber, 2-chamber and 3 chamber views: left ventricular internal dimension in diastole (LVIDd), left ventricular internal dimension in systole (LVIDs), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial volume (LAV), left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), peak mitral orifice flow velocity at early (E) and late (A) diastole, left ventricular ejection fraction (LVEF) calculated by biplane Simpson method, the average value of septal and lateral mitral annulus velocity at early diastole (e’), and the E/A and E/e’ ratios. LVM, LVEDV, LAV were indexed to body surface area (BSA). Echocardiographic examination was performed immediately after brachial cuff blood-pressure measurement, which was assumed to be equal to peak systolic LV pressure.Image cine-loops were analyzed by a dedicated software . In the automatic functional imaging mode, myocardial deformation measurements were performed using tissue speckle tracking and the displacement of speckles of myocardium in each spot was analyzed and tracked frame by frame. After manual tracing of the endocardial border of the end-systolic frame  and adjusting the appropriate region of interest (ROI)  between the endocardium and epicardium, a bull's-eye map of the overall longitudinal strain (LS) of LV was obtained by automatic frame-by-frame tracking of the acoustic markers in the myocardial tissue. The ROI was adjusted manually until the tracking quality was scored as acceptable. After inserting the blood pressure measurements manually, the software then constructed a non-invasive LV PSL according to the duration of isovolumic and ejection phases defined by valvular timing events, which were defined by the opening and closure of the mitral and aortic valves. The area within the PSL provided an index of myocardial work as described by Russell et al. . The folTo enable the investigation of regional strain and work distribution in the LV, the ventricle was divided into 18 segments. Three regions  were each divided into six segments, enabling an investigation of the regional characteristics in each plane . The mea2 test. Univariate and multivariate logistic regression analyses were performed to identify independent factors for LV hypertrophy. Odds ratio (OR), 95% confidence interval (95% CI), and P value were reported as the results of logistic regression analysis. Receiver operating characteristic (ROC) analysis was performed to identify the optimal cutoff point of GLS, GWE, Api-LS and Api-MWE to discriminate LV hypertrophy. Intraclass correlation coefficients (ICC) were calculated for interobserver and intraobserver agreement in 15 randomly selected patients. Myocardial strain was re-measured to calculate myocardial work parameters from the same images by two independent observers who were blinded to all other patient data. The intraobserver reproducibility was achieved by the same observer at 1-week interval between the first and second measurements. Graphpad prism 6.0 was used for all data graphing. A value of P < 0 0.05 was considered statistically significant.SPSS version 24  was deployed to perform the statistical operations. Continuous variables were summarized as mean values ± standard deviation (SD). Categorical variables were presented as numbers and percentages. Analysis of variance (ANOVA) was used to assess multiple comparisons among groups. Post-hoc comparisons were assessed with the Bonferroni correction. Differences between categorical variables were analyzed using the χP < 0.001).Clinical characteristics of the five groups are presented in Table P < 0.001). Compared with controls, LVEF was significantly decreased in CH and EH groups (P < 0.001), a phenomenon preserved in NG and CR groups. Diastolic function parameters revealed significantly reduced e’ and increased LAVI in HT subgroups (P < 0.001). Moreover, E/e’ was significantly elevated in CH and EH groups (P < 0.001).In Table P < 0.001). GWI and GCW did not change across the different LV remodeling groups. GWW was increased and GWE was reduced in both CH and EH group (P < 0.001), as shown in Table The GLS showed a gradual decrease  in the HT sub-groups (P < 0.001), while Api-LS was decreased only in CH and EH groups. Basal MWI and MCW were decreased only in the CH and EH groups . Apical MWI and MCW were increased in the NG and CR groups . Middle MWI and MCW did not vary among the HT subgroups. All segmental MWW were elevated and all segmental MWE were reduced significantly in the CH and EH groups (P < 0.001) . The optimal cutoff for Api-LS was -23.08% . The optimal cutoff for Api-MWE was 97.92% .The ROC curves of LS (GLS and Api-LS) and MWE (GWE and Api-MWE) were used for discriminating hypertensive LV hypertrophy, as shown in Fig. P < 0.001) and the inter-observer ICC was 0.950 . For GCW, the intra-observer ICC was 0.923  and the inter-observer ICC was 0.938 . For GWW, the intra-observer ICC was 0.928  and the inter-observer ICC was 0.929 .Fifteen patients were randomly selected, and the GWI, GCW, GWW were evaluated for intra- and inter-observer reproducibility. For GWI, the intra-observer ICC was 0.950  this was a single-center study with small sample size, especially in the CR group. Thus, a larger multi-center study is needed in the future to validate the current findings. 2) For ethical purposes, all patients were enrolled without an interrupted medication course, which resulted in the absence of subjects with a severe elevated blood pressure. Our study was thus only able to describe myocardial work across patients with various patterns of LV geometry with present afterload conditions.In the early stages of LV remodeling, apical myocardial work is increased as a compensatory mechanism, playing an important role in the maintenance of global myocardial work. During the later stages, apical myocardial work decreases gradually, resulting an obvious decreased GWE. Myocardial work parameters are useful as non-invasive tools for the assessment of myocardial function. Further, segmental myocardial work analysis offers the opportunity to explore the distribution of myocardial impairment in HT more dynamically.Additional file 1.


The safety of prolonged high-altitude stays and exercise for physically fit post-myocardial infarction (MI) patients is unclear. Myocardial tissue hypoxia and pulmonary hypertension can affect cardiac function and electrophysiology, possibly contributing to arrhythmias. We included four non-professional male athletes, clinically stable after left ventricular MI (three with ST-segment elevation MI and one with non-ST-segment elevation MI) treated with drug-eluting stents for single-vessel coronary artery disease. Oxygen levels were reduced to a minimum of 11.8%, then restored to 20.9%. We conducted electrocardiography (ECG), ergometry, and echocardiography assessments in normoxic and hypoxic conditions. With an average age of 57.8 ± 3.3 years and MI history 37 to 104 months prior, participants experienced a significant increase in QTc intervals during hypoxia using Bazett’s (from 402 ± 13 to 417 ± 25 ms), Fridericia’s (from 409 ± 12 to 419 ± 19 ms), and Holzmann's formulas (from 103 ± 4 to 107 ± 6%) compared to normoxia. This effect partially reversed during recovery. Echocardiographic signs of pulmonary hypertension during normobaric hypoxia correlated significantly with altered QTc intervals (p < 0.001). Despite good health and complete revascularization following MI, susceptibility to hypoxia-induced QTc prolongation and ventricular ectopic beats persists, especially during physical activity. MI survivors planning high-altitude activities should consult cardiovascular specialists with high-altitude medicine expertise. Adverse consequences, like myocardial tissue hypoxia and pulmonary hypertension (PH), could impact cardiac function, electrophysiology, and predispose to arrhythmias. Sympathetic activation and cellular transmembrane potassium shifts exacerbate arrhythmia risk, especially at very high altitudes. Patients post myocardial infarction may be prone to ventricular arrhythmias depending on revascularization2, concomitant pharmacotherapy, left ventricular impairment, and myocardial scarring3.Altitude exposure exceeding 4200 m warrants careful consideration in patients with ischemic heart disease4, was equivalent to an altitude of approximately 4500 m. Furthermore, we performed echocardiography and assessed whether the alterations in ECG are associated with hypoxia-induced PH  in patients with previous myocardial infarction. Normobaric hypoxia, simulating high-altitude conditions and replicating high-altitude pulmonary hypertension (PH) PH Fig. .Figure 1Inclusion criteria encompassed patients with a history of prior myocardial infarction, fully revascularized left anterior descending (LAD) lesions, overall good health, physical fitness, and prior altitude tolerance exceeding 2000 m. Patients were clinically stable in the preceding 12 months and had previously tolerated altitudes of > 2000 m.Exclusion criteria covered myocardial infarction within the last 12 months, non-LAD culprit lesion, incomplete revascularization during percutaneous coronary intervention (PCI), multivessel coronary artery disease, significant pre-existing lung disease, left ventricular ejection fraction (LVEF) < 35%, regular angina pectoris, cardiac decompensation within the past year, absence of heart failure medication, and blood parameter abnormalities, particularly thrombocytosis.https://www.dlr.de/envihab/en/desktopdefault.aspx/), we gradually decreased atmospheric oxygen (FIO2) to a minimum of 11.8% (hypoxia), which equals the oxygen content at ≈ 4500 m, over a period of 14 days. FIO2 of 11.8% was maintained for 4.5 days followed by return to normoxia within two days. Subjects received a standard normocaloric diet with four meals per day. Following a structured daily schedule, subjects woke up at 7 a.m., spent 15 h awake performing light activities, and went to bed at 10 p.m. Each subject completed 60 min of aerobic exercise daily on a treadmill or bicycle. We obtained 12-lead resting ECG daily. Transthoracic echocardiography was performed on the second day of acclimatization and daily at 11.8% FIO2, and during the first two days of recovery at 20.9% FIO2 to assess echocardiographic signs of PH . We submitted participants to exercise ECG with 25 W increments until exhaustion on a bicycle ergometer under normoxia, and under 17.5% FIO2 (~ 1500 m) but for safety reasons not during more intense hypoxia.In the DLR:envihab hypoxia module , approved by the local ethics committee of the North Rhine Medical Association in Düsseldorf, Germany (“Ärztekammer Nordrhein”) and conducted in accordance with the Declaration of Helsinki after obtaining informed consent from all subjects. All methods were carried out in accordance with relevant guidelines and regulations.Results are presented as mean ± standard deviation. Pearson correlation between any two variables were calculated and accompanied by a "Wald-type" p-value based on bootstrap standard errors. Differences in mean values over conditions were evaluated by linear mixed models with fixed effect condition and random effect subject. Differences between paired measurements were tested by the (exact) Wilcoxon signed-rank test. Additionally, Friedman test was applied to assess significant differences among multiple related groups with non-normally distributed dependent variables.2; VO2 max, 32–43 mL/kg per minute) who were in clinically stable conditions 37 to 104 months following left ventricular myocardial infarction. Three participants had experienced ST-segment-elevation myocardial infarction (STEMI), while one had a history of non-ST-segment-elevation myocardial infarction (NSTEMI). In each participant, effective revascularization was achieved by subsequent drug-eluting stent intervention, targeting an isolated stenosis within the mid-to-ostial segment of the LAD artery. Two women were excluded, one due to thrombocytosis and the other due to right ventricular involvement5. An additional male participant (aged 60 years), who was athletically active and had no previous history of myocardial infarction, was included as a control. Transthoracic echocardiography revealed distinct left ventricular wall motion abnormalities and corresponding LVEF for each patient: Patient 1 presented with apical, anteroseptal, and anterolateral akinesis (LVEF = 50%); Patient 2 showed apical, septal, anterior, and apical inferior akinesis (LVEF = 36%); Patient 3 exhibited apical and apical septal hypokinesis (LVEF > 50%); and Patient 4 had no abnormalities (EF = 58%). Following myocardial infarction, all participants received standard medical treatment, including aspirin for two out of four, marcumar for one out of four, anti-Xa-antagonist for one out of four, statins for all four, ACE inhibitors/AT1 antagonist for all four, azetidinone for one out of four, β-blockers for one out of four, and dihydropiyridine for one out of four5.Of the initially screened 11 patients, we included four male recreational athletes , Fridericia's (from 409 ± 12 to 419 ± 19 ms), and Holzmann’s (from 103 ± 4 to 107 ± 6%) formula compared to normoxia  and magnesium levels  increased within normal ranges during hypoxia. Normobaric hypoxia-induced PH, which subsequently reversed during the return to normoxia , with baseline mean values at 8.0 ± 1.8, declining to 7.0 ± 1.3 during hypoxia, and further to 6.4 ± 1.4 during recovery. No significant ST segment depressions were detected throughout the respective study phases.Multiple echocardiographic indicators of PH demonstrated significant correlations with the altered QTc intervals . LVEF improved significantly during and after hypoxia exposure , with baseline, hypoxia, and recovery mean values of 51.2 ± 12%, 58.8 ± 16%, and 62.6 ± 13%, respectivelyMaximal exercise performance decreased by 12% during hypoxia compared to normoxia (262.5 ± 45.1 vs. 231.3 ± 81.7 watts), accompanied by a corresponding 10.1% reduction in peak VO2 from 38.6 ± 4.2 to 34.7 ± 7.5 mL/min/kg. In comparison to normoxia, ventricular premature beats (VES) occurred more frequently during exercise in hypoxia , particularly at lower exercise loads (125.0 ± 134.6 vs. 158.3 ± 82.5 watts; Fig. The datasets that support the findings of this study are available from the corresponding author upon reasonable request.1. QTc interval prolongation is also common in chronic PH with impaired right ventricular function6. While cardiac output and hematocrit adjustments usually maintain systemic oxygen delivery1, microcirculatory dysfunction-induced tissue hypoxia may affect cardiac electrophysiology. There is no evidence of a significant risk of fatal arrhythmias from hypoxia in healthy individuals1. However, in patients with heart diseases, QTc interval prolongation and VES should be taken seriously7.The key finding of our study is that clinically stable and physically fit post-myocardial infarction patients exhibit QTc interval prolongation in response to hypoxia-induced PH. Additionally, VES occur more frequently during and after exercise, even at altitudes equivalent to approximately 1500 m, likely due to hypoxia-induced PH and sympathetic activationLimitations include the small sample size consisting of only four participants and the exclusive inclusion of male participants, which restrict the generalizability of our findings to a broader post-myocardial infarction population. Additionally, asymptomatic electrocardiographic changes may not directly predict clinical outcomes. Moreover, variability in patients' ejection fractions has the potential to introduce heterogeneity in the study population. Furthermore, the inclusion of a patient with NSTEMI, characterized by distinct pathogenesis and myocardial scar mass compared to STEMI, could confound result interpretation. Given the pilot nature of this study, our preliminary findings require careful consideration.Despite these limitations, our study indicates that even exceptionally healthy, fully revascularized post-myocardial infarction patients may be susceptible to hypoxia-induced QTc interval prolongation and VES, particularly during physical exertion. Albeit the clinical implications of these findings may warrant further investigation, we recommend cardiovascular evaluation by a high-altitude medicine specialist for post-myocardial infarction patients planning high-altitude physical activities. Future research should investigate the efficacy of hypoxia-induced cardiovascular stress testing in guiding such decisions.