Here, we describe the rationale along with the protocol for a clinical trial to test the following hypotheses: (1) compared with the control group, VO2 peak will be increased in both the moderate-intensity continuous training (MICT) and HIIT groups and (2) compared with the control group, myocardial fibrosis due to MI will be improved by HIIT and MICT.High-intensity interval training (HIIT) is an emerging method of cardiac rehabilitation, which is more and more popular in recent years. Research into the effect of HIIT on peak oxygen uptake (VO2 peak will be tested by cardiopulmonary exercise testing (CPET) and myocardial fibrosis will be evaluated by cardiac MR. A variety of blood and psychometric tests and also the peripheral arterial tonometry, reactive hyperemia index for microvascular endothelial function, and microvascular blockage or digital vasomotor response are included.This is a single-center, randomized controlled clinical trial. In total, 180 patients with MI are to be recruited for this study. VOThe ethics committee of the Guangdong Provincial People's Hospital has authorized this mechanistic clinical research. Peer-reviewed articles and conference presentations will be used to disseminate the findings.NCT04863677. More than 7 million people suffer from acute myocardial infarction (AMI) worldwide each year . And in n = 1,970) or improved conventional treatment with educational counseling . The researchers found the Yoga-CR group had a greater return to preinfarct (2peak) is the gold standard for determining functional limitations and the integrative physiology of the circulatory, respiratory, muscular, cellular, and oxidative systems  decreases by 15%  is defined by repeated high-intensity movements, interspersed with low-intensity recovery periods. Moderate-intensity continuous training (MICT) improves endurance mainly, demonstrating an inferior effect on VO2 peak compared with HIIT  will prolong the survival time of patients with MI, decrease the risk of readmission and enhance the quality of life –6. Multieinfarct , short-teinfarct . Given t systems , 14. Exeorbidity . The purith HIIT . Despitel muscle . In addil muscle . The enel muscle . Dun et l muscle  discoverl muscle . It is wFollowing MI, cardiomyocyte necrosis initiates an inflammatory cascade that clears the wound of dead cells, induces collagen production, activates myocardial fiber cells, and retains the ventricle's structural integrity . When myCardiac magnetic resonance (CMR) is a non-invasive method for evaluating CHD. It is the gold standard technique for assessing myocardial fibrosis and cardiac function, and scarred myocardium in patients with MI . Edema, 2peak and myocardial fibrosis in patients with MI. The secondary objective is to assess the effect of HIIT, MICT, and guideline-based physical activity on endothelial function, body mass index (BMI), arrhythmias, and inflammatory markers.The main objective of the study is to explore the effect of HIIT, MICT, and guideline-based physical activity on VOThis study is now being carried out at the Guangdong Provincial People's Hospital in Guangzhou, Guangdong, China. The research methodology and procedures (No. GDREC2020208H(R1)) were approved by the ethics committee of the Guangdong Provincial People's Hospital.The HIIT on MI study is an ongoing randomized controlled trial (RCT), followed up with a 1-year observing period. The first patient was recruited on April 2021. This study is to be completed by March 2024. After completing a written permission form, patients are evaluated to see whether they are eligible.2peak, cardiac fibrosis, endothelial function, microvascular obstruction, arrhythmia, body fat, inflammation, and psychological effects on participants. The schematic design of the study is shown in A 12-week cardiac rehabilitation training program  will be studied to determine the impact of HIIT and MICT on VO(1) Age range: 18 to 75 years.via the Fourth Universal Definition of Myocardial Infarction). The term “acute myocardial infarction” must be utilized when there is medical evidence of acute myocardial ischemia along with a detection of a fall and/or rise in cTn values with manifestations of myocardial ischemia; new alterations in ischemic ECG; developing pathological Q waves; images exhibiting prove of new loss of viable myocardium or new abnormality of regional wall motion in a pattern congruent with an ischemic etiology; and determination of a coronary (not for type 2 or 3 MIs).(2) Individuals with AMI who were treated with revascularization 6–12 weeks after the beginning of the AMI and harbored a New York Heart Association functional classification (NYHA) Class I–III; (AMI verified (3) Able and willing to finish the CR program independently, as determined by the informed consent form.(4) Complete cardiopulmonary exercise testing (CPET) during enrollment or within 1 month of receiving the CPET result.(1) onduct high-intensity exercise regularly.(2) Currently enrolling in any other clinical trials.(3) Have any other significant health condition in the preceding year .(4) Dementia; infirmity; or inability to participate in sports .(5) Acute liver failure with severe complications.(6) Acute renal failure with severe obstructive nephropathy.T ≥ 38.5 or ≤ 36°C, SpO2 ≤ 90%.(7) Irregular vital signs: heart rate at rest <40 or > 120 bpm, or blood pressure: systolic blood pressure > 200 mm Hg, diastolic pressure > 110 mm Hg, (8) Inspectors at the site determine that the patient will be unable to finish the trial and/or attend follow-up.If the patient has ischemic performance during exercise, such as chest pain and chest tightness, immediately stop exercise, and re-evaluate. According to the assessment of professional cardiologists, if surgery is needed, surgical treatment will be carried out, and such patients will withdraw from the study. If it can be relieved after rest, a new exercise plan will be re-established.a priori followed by an F test was performed. Since there is no previous reference for similar research data, the effect size of the observable indicator in this study is set to be 0.25. To achieve more than 80% power and a 2-sided critical threshold of 0.05, each arm must contain a minimum of 53 patients. Estimating a 10% loss to follow-up, the recruitment goal is 60 patients per arm (n = 180).Based on the degree of myocardial fibrosis at the primary endpoint, the sample size was estimated using G Power3.1.9.4, one-way ANOVA, and 2 peak, based on our pre-experiment, the mean increase of peakVO2 in control, MICT, and HIIT groups after exercise training is −0.18, 2.86, and −0.36 ml/kg/min, and the standard deviation of the difference between groups is 2.92, 3.38, and 2.74. By one-way ANOVA F-tests, sample sizes of 18, 18, and 18 are obtained from the 3 groups whose means are compared. The total sample of 54 subjects achieves 80% power to detect differences among the means of peakVO2 using an F-test with a 0.05 significance level. Estimating a 10% loss to follow-up, the recruitment goal is 20 patients per arm (n = 60).As for VOTaking two primary endpoints together, the recruitment goal is 60 subjects per arm.Patients who are both the eligible and willing are randomized in a 1:1:1 ratio (block randomization). The computer generated a random number table with values ranging from 1 to 180 (including shedding instances). Each participant in each group will be allocated a case number in accordance with the sequence of grouping, and each case number will relate to group 1, 2, or 3 according to the random number.Supervised exercise training will be performed 3 times per week at the CR center in the Guangdong Provincial People's Hospital. All patients are assigned at random in a 1:1:1 ratio to one of three groups: HIIT (group 1), MICT (group 2), or control group (group 3). This program consists of 36 CR sessions and typically lasts 12 weeks (3 sessions per week).All patients receive drug treatment after MI, routine health education, and postoperative medication guidance according to the guidelines. The control group receives no extra rehabilitation or physical activity. Patients in the groups 1 and 2 perform MICT during the first week of CR, after which, they will enter the corresponding group according to the random number of the entry period.2 data. According to the percentage of peakVO2 to design exercise training programs: high strength refers to 85 to 100% peak VO2 and 85% peak VO2 is higher than the anaerobic threshold (AT); medium intensity: 40 to 60% peak VO2, and 60% peak VO2 is less than AT; and low intensity means 20% peak VO2. The exercise intensity also could be micro-adjusted according to the rating of perceived exertion (RPE) during the actual cardiac rehabilitation exercise. Short bursts of high-intensity exercise are alternated with intervals of low-intensity activity in HIIT programs (active recovery). HIIT constitutes twenty intervals of high effort  of 15–17) along with a low intensity  of 10 or completely rest). It takes about 40–50 min to complete the entire training cycle .According to the 2020 European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes and the 2019 Chinese guideline of acute MI. A loading dose of 150–300 mg (or 75–250 mg) of aspirin is advised for all patients without adverse effects, and a maintenance dose of 75–100 mg od for long-term treatment . Unless there are adverse events or a considerable risk of bleeding, aspirin should be taken for at least a year . In all the patients with MI, statins are indicated. Low-density lipoprotein cholesterol contents must be reduced by at least 50% from pretreatment levels, or below 1.4 mmol/l (55 mg/dl) . Unless contraindicated, angiotensin-converting enzyme (ACE) repressors [or angiotensin receptor blockers (ARBs)] in cases of intolerance to ACE repressors are recommended to minimize all-cause, and cardiovascular mortality along with morbidity in individuals with heart failure, diabetes, or chronic kidney disease . For a long period, all patients with MI should be treated with ACE inhibitors or ARBs . Beta-blockers are advised for those who have heart failure [left ventricular ejection fraction (LVEF) 40%] or systolic left ventricular dysfunction . In those who have had a prior MI, long-term oral beta-blocker medication should be explored to minimize all-cause along with cardiovascular mortality, and cardiovascular morbidity   (ventilation) along with VCO2 (carbon dioxide production) breath by breath. Heart rate and SpO2 are assessed via pulse-by-pulse filtering fingertip oximeters. VO2 peak is the highest value of oxygen uptake obtained during the exercise. The VE/VCO2  slope is determined via plotting the linear regression slopes of VE and VCO2 from the first second of exercise to the respiratory compensation point, which occurs when acidemia-triggered ventilation along with end-tidal partial pressure of carbon dioxide (PETCO2) start to decline. The AT is the VO2 level at which the VE/VCO2 ratio begins to drop or remains constant while the ventilatory equivalent to oxygen (VE/VO2) ratio continues to escalate. The ΔSpO2 is calculated by subtracting the peak SpO2 from the rest SpO2. The volume of oxygen at the ventilatory threshold (VT) is the beginning point for ventilation to grow at a quicker pace than oxygen consumption. The highest power output generated by the participant is known as the workload peak. The level of power output generated at VT is known as workload @VT  r/min, complete exercise tests in 8–12 min until symptoms limit. Patients may interrupt the test if they experience dyspnea, leg weariness, symptoms (such as chest pain and dizziness), or any other unbearable discomfort. Continuous electrocardiography, gas exchange, and blood pressure along with SpOload @VT –34.via native along with postcontrast T1 mapping approaches adjusted to the patient's hematocrit. In this study, we evaluate myocardial fibrosis in patients with MI by CMR at 6 weeks and re-examined CMR 3 months later.All patients in each group were chosen to have their cardiac fibrosis assessed using CMR at two different times: before the trial began and after the third month of follow-up. CMR is the gold standard for non-invasive cardiac tissue characterization. CMR allows late gadolinium enhancement techniques to characterize focal alternative fibrosis. CMR may also be employed to evaluate diffuse myocardial fibrosis by quantifying the extracellular volume fraction All the patients have dynamic electrocardiogram and echocardiography recorded at the start of the research and the third month of follow-up. Without knowing the precise clinical situations, the data were independently assessed by two qualified doctors using the double-blind procedure.Several blood samples will be obtained: before the start of the study, the first month of follow-up, and the third month of follow-up. We will detect blood routine, liver function, renal function, lipid metabolism, interleukin-6 (IL-6), platelet aggregation rate, n-terminal pro-brain natriuretic peptide (NT-proBNP), hypersensitive troponin T, stromelysin-2 (ST-2), and metabolomics measurements. We will evaluate the changes of pathogenesis from the aspects of the inflammatory mechanism, the humoral immunity index, and metabolomics measurements.The Endo-PAT2000  will be used to examine peripheral vasoconstriction along with microvascular function. The Endo-PAT2000 employs a volume plethysmography approach to quantify peripheral blood volume fluctuations by measuring the finger pulse volume amplitude (PVA) . The reaWe will use SF-36 to assess the quality of life. It consists of eight parts: general health, physical functioning, bodily pain, role physical, vitality, social functioning, mental health, and role emotional. SF-36 will be recorded at the start of the research and the third month of follow-up.2 peak after 12 weeks of exercise training in the three groups , and changes in myocardial fibrosis in the three groups.Primary outcomes: changes in VOSecondary outcomes: changes in ST-2, endothelial function, microvascular obstruction, body fat, BMI, the incidence of arrhythmia, and quality of life in three groups after 3 months.2 peak will be increased in both the MICT and HIIT groups. The HIIT group may be more effective than the MICT group.(1) Compared with the control group, VO(2) HIIT may improve myocardial fibrosis in patients with AMI.(3) Compared with the control group, the quality of life will be significantly improved in the MICT and HIIT groups with higher cardiac ejection fraction, improved vascular endothelial function, and lower body fat.(4) The incidence of arrhythmia will be relatively low in the MICT and HIIT groups.2peak is likewise a strong individual predictor of mortality and morbidity. We predict that VO2peak will be increased in both the MICT and HIIT groups, and it will be higher in the HIIT group.Exercise-based CR is recommended as a helpful therapy for patients with MI to achieve a healthy lifestyle, and manage risk factors, to reduce all-cause along with cardiovascular mortality . The data of CR on patients with AMI mainly come from the end of the last century; however, the clinical management of AMI has changed in the past 30–40 years. The traditional MICT is generally used as the main method to rehabilitate patients with CHD and halt weight gain. Recent studies have found that HIIT may be more effective at increasing cardiopulmonary fitness, improving vascular function, reducing subcutaneous and abdominal body fat, reducing all-cause and cardiovascular mortality, and cardiovascular morbidity, improving insulin resistance than MICT , 21. VO2After MI, myocardial fibrosis will continue to develop, which can result in malignant arrhythmia and cardiac death. New evidence from epidemiological studies and observations suggests that exercise can improve myocardial fibrosis. There are other studies that show that long-term exercise training with repetitive exposure to prolonged vigorous exercise may increase cardiac fibrosis. Myocardial fibrosis was shown to be highly linked with cumulative exercise dosage . The effThe studies involving human participants were reviewed and approved by the Ethics Committee of Guangdong Provincial People's Hospital [No. GDREC2020208H(R1)]. The patients/participants provided their written informed consent to participate in this study.The research was conceived and designed by HM, LG, QG, and LX. XS, XQ, and XC recruited participants, drafted, and revised the manuscript. WL, XL, and HL made significant contributions to the project's conceptualization and design. HM, XS, and XQ managed the clinical practice organization, and finished the statistical analysis. Each author edited the text critically for significant intellectual content and gave final approval to the published version.This research was supported by the grants from National Natural Science Foundation of China (No. 8160284), Natural Science Foundation of Guangdong Province , Start-up Funding of National Natural Science Foundation of China , the National Key R&D Program of China (No. 2018YFC2001805), Guangdong Medical Science and Technology Research Fund, China (2019118152336191), Guangzhou Science and Technology Foundation and Application Foundation Research Project (Nos. 202102080368 and 202102080033), Traditional Chinese Medicine Bureau of Guangdong Province (20201008), Leading Medical Talents Project in Guangdong Province  (No. KJ012019431), and High-level Hospital Construction Project of Guangdong Provincial People's Hospital .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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AimPrimary hyperthyroidism (PHPT) is known to affect left ventricular structure and function and may contribute to increased cardiovascular morbidity and mortality. Whether parathyroidectomy (PTX) reverses left ventricular hypertrophy/remodeling among PHPT patients remains controversial.MethodIn this prospective, single-center study, we enrolled patients with the diagnosis of PHPT who were scheduled for PTX. Patients underwent a complete biochemical workup and an echocardiographic examination at baseline and a six-month follow-up. The primary objective was to compare the left ventricular mass index (LVMI) at baseline and six-month follow-up.ResultEighteen patients  were enrolled. PTH and serum calcium returned to normal immediately post-PTX and remained normal at six months. LVMI at baseline was within normal limits and reduced further at the six-month follow-up. The left ventricular ejection fraction was in the normal range before the PTX and remained unchanged during follow-up.ConclusionCurative PTX reduced LVMI further within the normal range at six months in patients with asymptomatic hyperparathyroidism, providing evidence for benefit in an important non-traditional disease manifestation. Primary hyperparathyroidism (PHPT) is characterized by inappropriately increased secretion of parathyroid hormone (PTH) from the parathyroid glands. PTH is the key regulator of calcium and phosphate metabolism. The typical electrolyte disorder in PHPT is hypercalcemia, whereas a normocalcemic form of PHPT was recognized almost 15 years ago. The classical clinical presentation is characterized by overt involvement of kidney and bone, while the non-classical disease manifestations include cardiovascular, gastrointestinal, psychiatric, neurocognitive, and quality of life issues  + 0.6. The left ventricular mass index (LVMI) was calculated as LVM divided by body surface area [2 for women and 49-115g/m2 for men. Left Ventricular Ejection Fraction (LVEF) was measured based on Simpson’s biplane formula and it was considered normal when measured ≥55% [Echocardiographic evaluation was conducted at the hospital’s echocardiography core lab according to the guidelines of the American Society of Echocardiography using a GE Vivid S5 ultrasound machine. Left ventricular end-diastolic dimension (LVEDD), interventricular septal thickness at end-diastole (IVSd), and posterior wall thickness at end-diastole (PWd) were measured. Left ventricular mass (LVM) was calculated using the following formula: LVM (g) = 0.8 x 1.04 [(LVEDD + IVSd + PWd)ace area , 17. TheStatistical analysisAfter power analysis, it was estimated that a sample size of 18 patients would provide a power of 80% with a level of significance of 0.05 (two sided), for detecting an effect size of 0.75 between paired values. A drop-out rate of 10% was assumed and, thus, a total of 20 patients were needed.th edition) was used for the statistical analysis. Statistical significance was set to p<0.05. Shapiro-Wilk test was used to assess the normality of data distribution. The results are presented as means ± standard deviation, when normality was assumed. Student-t test for paired data was used to compare the means of continuous variables in two different times, given that normality was assumed.IBM SPSS Statistics software  were included in the analysis. Their baseline characteristics are presented in Table After PTX, mean PTH and albumin-corrected serum calcium levels normalized, immediately postoperatively and at six months. LVMI was normal prior to PTX in all 18 subjects. However, it was reduced significantly six months after curative PTX. LVEF was normal at the initial assessment and remained normal six months after PTX p=0.22)  [Available data regarding structural heart involvement in PHPT patients remain controversial. However, cardiac dysfunction has been widely reported among the published studies. In a recent study, left ventricle systolic and diastolic functions were assessed with specific echocardiographic techniques, namely the tissue Doppler imaging (TDI) and strain and strain rate echocardiography to evaluate myocardial systolic and diastolic function in 31 PHPT patients and 29 healthy controls and revealed that PHPT patients without any known underlying cardiovascular disease experience both subclinical systolic and diastolic heart dysfunction . However p=0.69) . Persson p=0.69) .2 (12.5%) on average after curative PTX in the immediate postoperative period but this effect was not sustained beyond six months [Many published studies support that left ventricular hypertrophy prevalence among patients with hyperparathyroidism is high and possibly reversible after PTX, at least in the short term . In addix months . This fix months , 30. In This study is subject to the limitations associated with real-world observational research. The main limitation is the small subject sample that does not allow safe conclusions. Duration of follow-up was limited to six months after surgery and it is questionable whether the benefit of PTX on LVMI wanes over time. Except for IVSd, PWd, LVEDD, LVMI, and LVEF no other echocardiographic analysis was made and no valve assessment was conducted. LVEF should ideally be combined with parameters such as longitudinal strain for a more thorough study of the systolic function. In addition, only patients with mild types of PHPT were included. However, nowadays, we rarely assess patients presenting with the classical form of PHPT. Furthermore, differences in outcome between men and women could not be made, since the majority of subjects were women. Finally, although adjustments for blood pressure measurements and antihypertensive medications were not made, the small proportion of patients with hypertension did not influence the results.In conclusion, curative PTX reduced mean LVMI at six months, in a small sample of patients with mild PHPT. LVEF remained in the normal range. These results are in accordance with previous findings suggesting a favorable, short-term effect of PTX on left ventricular function, but should be interpreted with caution and larger prospective studies in patients with mild, asymptomatic hyperparathyroidism are necessary for safe conclusions. However, this study primarily tried to raise the issue that cardiovascular impairment should be seriously under consideration when dealing with patients with PHPT.


Following a myocardial infarction (MI), the prognosis of patients is highly dependent upon the re‐establishment of perfusion not only in the occluded coronary artery, but also within the coronary microcirculation. However, our fundamental understanding of the pathophysiology of the tiniest blood vessels of the heart is limited primarily because no current clinical imaging tools can directly visualise them. Moreover, in vivo experimental studies of the beating heart using intravital imaging have also been hampered due to obvious difficulties related to significant inherent contractile motion, movement of the heart brought about by nearby lungs and its location in an anatomically challenging position for microscopy. However, recent advances in microscopy techniques, and the development of fluorescent reporter mice and fluorescently conjugated antibodies allowing visualisation of vascular structures, thromboinflammatory cells and blood flow, have allowed us to overcome some of these challenges and increase our basic understanding of cardiac microvascular pathophysiology. In this review, the elegant attempts of the pioneers in intravital imaging of the beating heart will be discussed, which focussed on providing new insights into the anatomy and physiology of the healthy heart microvessels. The reviews end with the more recent studies that focussed on disease pathology and increasing our understanding of myocardial thromboinflammatory cell recruitment and flow disturbances, particularly in the setting of diseases such as MI. Intravital imaging of the beating heart microcirculation in vivo has been challenging. The past 50 years has seen changes in ways to both stabilise and image the heart with a shift from learning about coronary vascular anatomy and physiology to the role of thromboinflammation and other microcirculatory disturbances in cardiovascular disease. This review will discuss the major surgical, technical and imaging innovations that have allowed this to happen. The resulting ischaemia leads to tissue death and development of a necrotic lesion called an infarct. Treatment focuses on rapidly re‐establishing perfusion which can be successfully achieved with a primary percutaneous coronary intervention (PCI), such as stenting, or by fibrinolysis using intravenous clot‐busting drugs. Revascularisation procedures, particularly primary PCI, have revolutionised the treatment of patients with an acute MI and significantly decreased mortality. However, despite this success, development of heart failure after an MI is the major driver of morbidity and mortality worldwide, placing a huge financial burden on healthcare resources Cowie, .Reperfusion, the only way to rescue the ischaemic heart, paradoxically leads to additional tissue damage, a condition termed ischaemia–reperfusion (IR) injury. If IR injury is significant, it can lead to heart failure and even death. This appears to be linked to tissue damage occurring subsequent to inadequate perfusion within the smaller blood vessels of the heart, namely the coronary microcirculation   swollen endothelial cells surrounded by cardiomyocytes that are themselves swollen (ii) presence of endothelial gaps (iii) red blood cell (RBC) congestion (iv) platelet and fibrin microthrombi and (v) a high number of intraluminal leucocytes or platelet‐leucocyte aggregates , generated more data than in vivo research in a shorter space of time.5, or a CX3CR1‐GFP+ reporter mouse whose monocytes expressed high levels of GFP. Elegant surgery connected the donor ascending aorta and pulmonary artery to the recipient's right common carotid artery and jugular vein, respectively, after which the donor heart resumed a regular heartbeat immediately following reperfusion. A small ring of Vetbond, a veterinary adhesive, was applied to the bottom of a coverglass contained within a stabilisation plate, and briefly held against the left ventricle of a partially exteriorised donor heart to secure it  and MAC‐1 (αMβ2 or CD11b/CD18). Reduced neutrophil crawling velocities, clustering and extravasation was noted in the absence of ICAM‐1 and Mac‐1, with LFA‐1 blockade preventing neutrophil adhesion and extravasation. These adhesion molecules have previously been demonstrated histologically and flow cytometrically to be important in myocardial leucocyte infiltration  or in host mice pre‐treated with antibodies to leucocyte integrins that interact with endothelial ICAM‐1, namely LFA‐1  coronary artery. No pacing of the heart was performed and mice were ventilated with room air but, nevertheless, were able to tolerate being imaged for at least three hours. Neutrophil recruitment was not noted in the absence of injury. Importantly, native and donor hearts showed similar neutrophil kinetics after reperfusion. It is for this reason that the group later continued with the transplant‐mediated IR injury model to define the upstream signals that orchestrated neutrophil trafficking , respectively, to the infarct, which was induced by permanent LAD coronary artery ligation. By sliding the probe over the heart, myeloid cell infiltration into both the infarcted and remote areas could be analysed. The number of LysM+ neutrophils and CX3CR1+ monocytes remained low in non‐infarcted tissue but both cell types infiltrated the infarcted tissue within hours of ligation. Interestingly, monocyte recruitment was higher, remained elevated over days and more rapid than that of neutrophils. This rapid response was in contrast to the generally accepted notion that neutrophil recruitment preceded that of monocytes in MI. Additional insights into the velocities of circulating and rolling monocytes in large coronary arterioles and venules were also presented. An unexpected abundance of monocytes crawling or slowly rolling on the vessel walls was also noted in the heart, which the authors concluded were monocytes ‘patrolling’ coronary vessels during steady‐state immune surveillance. This was the first direct evidence that active immune surveillance mechanisms existed in the heart. Indeed, it is now accepted that there are at least two mouse monocyte subsets, namely inflammatory (Ly‐6ChiCCR2hiCX3CR1lo) and patrolling (Ly‐6CloCCR2loCX3CR1high) monocytes. Inflammatory monocytes accumulate at sites of inflammation, where they can differentiate into macrophages or dendritic cells. However, patrolling monocytes survey the vasculature by constantly crawling along the endothelial surface and are therefore early responders to sterile inflammation and tissue repair  in which the cardiomyocyte membrane was double fluorescently labelled with tdTomato and eGFP and then imaged using multiphoton microscopy.Matsuura and colleagues from Osaka, Japan also developed a non‐gated beating heart imaging method . An extensive network of FITC‐BSA‐perfused capillaries was observed in healthy hearts, paralleling the arrangement of muscle fibres, with cross connections along their length. In contrast, IR injury was associated with multiple areas in which FITC‐BSA did not perfuse. This resulted in patchy areas that appeared devoid of any microvasculature, indicating poor functional capillary density. Indeed, in some fields of view, up to half the imaged area appeared non‐perfused Figure . FurtherOur model was also used, for the first time, to image exogenously administered haematopoietic stem/progenitor cell (HSPC) cell trafficking to the heart in vivo at a cellular level and, importantly, ascertain whether vasculoprotection was a critical therapeutic mechanism. We focused on cellular therapy as there has been intense interest in their use for cardiovascular diseases and we had also previously shown HSPCs to reduce inflammatory events in other vascular beds  for supporting the research used to generate some of the images in Figure 1234 for


The minimal dimension of critical isthmus regions may be less than 1 cm in more than 25% of circuits mapped.A 73-year-old man with history of dilated cardiomyopathy and left ventricular (LV) ejection fraction of 39%, complete heart block status post permanent pacemaker placement 15 years ago with upgrade to biventricular implantable cardioverter-defibrillator 2 years ago, presented with recurrent episodes of VT and appropriate implantable cardioverter-defibrillator therapies despite antiarrhythmic drug therapy with sotalol. Cardiac magnetic resonance imaging showed midmyocardial delayed enhancement with full-length midmyocardial scar from the basal anteroseptum to inferoseptum . He undeIn anticipation of mapping a septal VT, a linear multielectrode catheter  was placed in the septal right ventricular outflow tract (RVOT) and an ablation catheter  was positioned on the LV basal anterior septum via transseptal approach. A diagnostic 2F microcatheter  was placed into the distal coronary sinus to record within the AIV and SPV . During d, proving critical circuitry confined within the interventricular septum , a balloon technique was not implemented. However, VT remained reinducible at a faster rate and therefore additional ablation were performed at 50 W from the LV and RV septum. VT has not recurred for 9 months at the time of this report.A second VT with left bundle branch block morphology with VLMNA and TTN, are associated with VT recurrence rates that are among the highest in structural heart disease.LMNA variants in particular have been shown to have high rates of arrhythmia recurrence, progression of cardiomyopathy to end-stage heart failure, and high mortality.Catheter ablation for drug-refractory VT in patients with dilated cardiomyopathies, particularly in those with genetic mutations such as ,,Lamin cardiomyopathy classically involves the septum and periaortic region and seems to be predominantly related to reentry in and around regions of scar. Periaortic VTs have been increasingly described with regard to reentrant mechanism and circuit characteristics.,Prior studies have not demonstrated localized reentry completely confined within the intramural septum, which is the novelty of this report. These descriptions reiterated the propensity of LMNA to predominantly involve the septum,Strategies such as substrate modification via transcoronary venous ethanol may warrant further consideration, particularly when a full-length septal scar is present on magnetic resonance imaging, which portends a poor prognosis.Owing to high rates of recurrent VT associated with lamin cardiomyopathies, early collaboration and consultation with a heart failure team is warranted to discuss advanced management options, given modest outcomes from ablation and high risk of mortality from progression of heart failure. This case provides further mechanistic insights into the nature of septal VTs in this challenging patient population that may be entirely missed by traditional endocardial and epicardial mapping techniques.In midmyocardial septal scar substrates, SPV recordings may provide critical intramural information to elucidate the spatial dimensions and location of circuit-challenging VTs. Localized reentry recorded from a single bipole pair can be confined completely within the septum, which cannot be fully characterized from either endocardial surface.


Subclinical alterations in myocardial structure and function occur early during the natural disease course. In contrast, clinically overt signs and symptoms occur during late phases, being associated with worse outcomes. Identification of such subclinical changes is critical for timely diagnosis and accurate management. Hence, implementing cost-effective imaging techniques with accuracy and reproducibility may improve long-term prognosis. A growing body of evidence supports using cardiac magnetic resonance (CMR) to quantify deformation parameters. Tissue-tagging (TT-CMR) and feature-tracking CMR (FT-CMR) can measure longitudinal, circumferential, and radial strains and recent research emphasize their diagnostic and prognostic roles in ischemic heart disease and primary myocardial illnesses. Additionally, these methods can accurately determine LV wringing and functional dynamic geometry parameters, such as LV torsion, twist/untwist, LV sphericity index, and long-axis strain, and several studies have proved their utility in prognostic prediction in various cardiovascular patients. More recently, few yet important studies have suggested the superiority of fast strain-encoded imaging CMR-derived myocardial strain in terms of accuracy and significantly reduced acquisition time, however, more studies need to be carried out to establish its clinical impact. Herein, the current review aims to provide an overview of currently available data regarding the role of CMR in evaluating myocardial strain and biomechanics. Myocardial strain and biomechanics are the results of intrinsic normal functioning of the heart, expressing the dynamic interdependency between cardiac structure and its physiology. Usually, in the early stages, heart diseases are clinically silent, often resulting in a delayed diagnosis and poor prognosis. Recent technological advances have developed cardiovascular imaging modalities which are able to thoroughly characterize myocardial tissue and function. Nevertheless, studies evaluating their clinical utility in the diagnosis and prognosis of cardiovascular patients are still sparse. Their close description could provide valuable insights into myocardial functional performance . BrieflyCardiac magnetic resonance imaging (CMR) is the gold-standard imaging method used for characterizing heart function and tissue structure, thus providing important information about cardiomyocytes, interstitium, microvasculature, and metabolic abnormalities . FurtherLV myocardial contraction and relaxation are complex phenomena that involve various yet synergistic contractions of all three myocardial layers, thus ensuring hemodynamic stability and optimal LV systolic function. At a glance, there are two ways in which myocardial strain can be outlined: the Lagrangian strain, which provides contractility changes using the own myocardium as a benchmark, and the Eulerian strain, which assesses changes of specific tissue zones with fixed baselines, while the material points differ over time . The disThe main advantage of CMR-determined myocardial strain is in patients with a poor acoustic window in which STE-based ones are not determinable. Additionally, the intra- and inter-observer biases are significantly reduced . AnotherUntil now, invasive heart catheterization has been considered the gold-standard method to evaluate cardiac function by using pressure-volume loops, which are valuable markers of myocardial contractility and stroke work, especially by determining cardiac output, end-systolic (ESPVR) and end-diastolic (EDPVR) pressure-volume relationships, or cardiac elastance . RecentlThe purpose of this review is to provide an overview of currently available data regarding the clinical role of CMR in evaluating myocardial strain and biomechanics.The concept of continuum mechanics in a completely isolated media, along with the properties of cardiac tissue governates the functioning of the cardiovascular system. Thus, myocardial deformation and spatial dynamic geometry are strongly related to these phenomena ,15. MoreMoreover, myocardial strain and dynamic spatial geometry rely on myocardial contraction forces, which can be assessed using a specific mathematical model that includes the cardiomyocytes’ active tension and calcium ions concentration . LV wallThe primary task of the LV is to ensure continuous blood flow through the vessels during the cardiac cycle. LV function is majorly conditioned by myocardial contraction, end-diastolic filling pressures, and its dynamic geometry, but also by the integrity and correct functioning of heart valves ,25. InitAccordingly, using imaging methods, such as STE and, lately, CMR, deformations of all three myocardial fibers can be globally and regionally assessed, resulting in parameters with important diagnostic and prognostic values: global longitudinal (GLS), circumferential (GCS) and radial (GRS) strains. Various studies have confirmed their paramount roles in diagnosis, risk stratification, and prognosis prediction in many cardiovascular diseases . To idenAlthough echocardiography is considered the gold-standard imaging technique in assessing LV strain and strain rates, recently, increasing evidence has shown that some CMR techniques are able to appraise myocardial deformation using either specific acquisition variants or post-processing software . GrowingFrom a technical point of view, the first and foremost magnetic resonance system that has allowed a usable approach to assessing myocardial strain, functioning geometry, and active biomechanics is tissue-tagging CMR (TT-CMR), despite its poor spatial resolution . SubsequFurthermore, fast Strain-Encoding (fast-SENC) is a valuable CMR technique that uses myocardial magnetization tags, but the main difference from TT-CMR is that the tags are parallelly overlaid on the myocardium, allowing the evaluation of longitudinal and circumferential strain, while radial deformation remains unfortunately unquantifiable . Fast-SEOn the other hand, a post-processing software package that could be applied to standard b-SSFP-CMR would hypothetically be the most convenient option to assess LV strain and biomechanics. FT-CMR is an optical flow magnetic resonance method, being derived from the technique which evaluates the motion of fluids. With proper optimization and adjustments, FT-CMR images are comparable to those obtained using speckle-tracking echocardiography and being applicable to standard cine-CMR, it might become highly usable soon , but optIncreasing evidence supports the role of CMR in assessing LV myocardial strain in different categories of patients. FT-CMR can determine LV strain measurements in both 2-dimensional and 3-dimensional approaches, with the latter requiring more studies for appropriate validation . It has Recently, an interesting article sought to assay the capacity and accuracy of fast-SENC to evaluate LV volumes, function, and mass. Almost all the following measurements were precisely determined using fast-SENC, requiring under two minutes of the total study time and being way faster than standard cine-CMR. Nevertheless, LV end-diastolic mass was underestimated by 7% . Furtherp = 0.005, and provided significant incremental predicting value for it [In a recently published systematic review that evaluated the impact of GLS by both echocardiography and CMR in patients with acute myocardial infarction, it was shown that the latter technique exhibited major advantages in matters of tissue characterization and resolution, regardless of the acoustic window. Nonetheless, larger cohort studies are needed to objectify the real incremental prognostic value that might be deployed by CMR in terms of LV strain characterization . Moreovee for it . Similare for it . Likewise for it . Latterly, fast-SENC is gaining more and more ground even in patients with ischemic heart disease, due to its rapidity and reproducibility. In a recently published study, which sought to compare fast-SENC and FT-CMR with STE in patients with acute myocardial infarction, El-Saadi et al., have shown that in terms of GLS, fast-SENC provided higher values than FT-CMR, but without any statistical significance as compared to STE. Moreover, for GCS, the parameters determined by fast-SENC were almost equal to FT-CMR, while as concerns the regional strain in the infarct-related artery, fast-SENC had a significantly higher area under the curve in properly identifying the injured myocardial segments, in contrast with FT-CMR . FurtherIn patients with dilated cardiomyopathy, TT-CMR was able to accurately determine impaired LV strain parameters, even within the early stage of the disease . MoreoveMoreover, in patients suffering from hypertrophic cardiomyopathy, impaired GCS determined by FT-CMR along with LGE were found as independent predictors of ventricular tachyarrhythmias . In addiLastly, the role of the LV strain by CMR to identify subclinical myocardial impairment has been recently appraised. In paediatric patients with end-stage renal disease, GLS, GCS, and GRS by TT-CMR, along with LV ejection fraction and mass, were significantly inflicted, whereas GCS and GRS were associated with poor outcomes . FurtherThus far, the association between LV torsion , twist aAs previously stated by Rosen et al., when TT-CMR is used to determine LV torsion, the peak systolic LV twist is divided by the inter-slice distance to ensure standardization . RegardiLV torsion-to-shortening ratio, which is defined as the ratio between inner wall shortening and torsion at ejection, was developed to accurately characterize endocardial strain and wringing. Essentially, this parameter is a precise marker of subendocardial myocardial impairment, especially in subjects with LV hypertrophy . In patiOver and above, a co-dependency between LV wringing and myocardial scarring has been latterly reported. Intriguingly, reduced LV torsion, along with other abnormal LV systolic parameters, was strongly related to the magnitude of myocardial fibrosis evidenced by Masson’s staining . Due to As for LV twist, certain evidence concerning the impact of cardiac dysfunction on LV twisting is beginning to emerge to expand the clinical utility of CMR . FT-CMR Compelling evidence renders the utility of CMR-derived LV sphericity index in various cardiovascular diseases. Some reports have shown that LV sphericity is inversely associated with LVEF, LV torsion, and mass-to-volume ratio, as well as with both global and regional LV trabeculation indexes ,110. LikFurthermore, the LV sphericity index  is emergLV long-axis strain  is a novThe basic principle of cardiac active biomechanics can be summed up by the relationship between the pressure and volume gradients that develop throughout every cardiac cycle. The close connections between these two physical phenomena have deployed specific pressure-volume curves, which can be used to accurately assess cardiac function. Moreover, specific surrogates of cardiac biodynamics which can precisely estimate myocardial contractility, ventricular-arterial coupling, end-systolic (ESPVR), and end-diastolic (EDPVR) pressure-volume relations can be derived from such measurements. However, the main disadvantage of these measurements is that, until now, they could have been accurately determined only by invasive conductance catheterization ,123.Recent studies have begun to deploy hybrid methods that may assess these parameters by combining cine- and velocity-encoded CMR with transient closure of IVC with venous catheters, thus mimicking the preload reduction in cardiac volumes. It was shown that CMR can evaluate the topmost right ventricular pressure during isovolumic normal heartbeats. This may be used to determine ESPVR , yieldinLikewise, using a similar principle, few pilot studies rendered the utility of CMR to determine EDPVR. In the study of Schmitt et al., pressure-volume curves were initially determined invasively by conductance catheterization. Afterward, using cine- and velocity-encoded CMR along with cardiac pre-load decrease by temporary inferior vena cava occlusion, the authors deployed a hybrid method to estimate EDPVR as a marker of LV stiffness. Not only did they succeed to demonstrate excellent agreement between the two methods, but these measurements were dynamically influenced by pharmacological stress, thus improving diastolic function parameters in a similar manner to those determined strictly by conductance catheterization. Nevertheless, these promising findings require larger studies to validate their clinical utility . AdditioMoreover, the clinical efficacy of these was first evaluated in murine models by Faragli et al., who sought to assess the relationship between determined LV strain parameters and hemodynamical parameters such as cardiac index, cardiac power output, and ESPVR determined by FT-CMR in various stress conditions. Despite several technical and analytical drawbacks that relatively lowered the statistical power, LV global longitudinal and circular strain were closely related to all LV hemodynamic measurements, regardless of the inotropic state, while LV global longitudinal performed best in assessing LV contractility, similar to LVEF. Therefore, FT-CMR might become a promising technique for evaluating LV hemodynamics; however, future studies are required for the optimization of this method . Last but not least, by creating a time-variance elastance mode, Seeman et al., were the first to develop a completely non-invasive method that uses solely CMR and brachial pressure to assess LV pressure-volume loops, thus overcoming the need for IVC occlusion. Firstly, they tested and validated this method in murine models and further confirmed it in human subjects by comparing patients with heart failure with healthy controls .Even though the role of CMR in determining myocardial strain and biomechanical parameters is gaining serious ground, there are still many uncertainties that need to be unraveled. FT-CMR has been proven to be a useful CMR method in assessing myocardial strain, but there is still insufficient evidence in terms of various cardiovascular diseases. Further studies should be conducted in patients with valvular heart disease, such as aortic stenosis or mitral regurgitation, in order to test the predictive ability of myocardial strain parameters in prognosis prediction. Moreover, there are not any available data regarding the role of FT-CMR-derived myocardial strain in patients with cardiac amyloidosis or other infiltrative heart diseases, which might provide information of tremendous importance in risk stratification and prognosis prediction. Further studies could also aim to test the ability of FT-CMR in creating multi-parametric predictive models based on LV wringing parameters in various cardiomyopathies or myocarditis. Additionally, there is little evidence of the role of FT-CMR-derived strain and biomechanics in patients with acute myocarditis.As for fast-SENC, it is a promising valuable CMR imaging technique that might enter day-to-day practice in the future, but more studies still need to be conducted. Although few studies have shown the superior ability of fast-SENC-derived myocardial strain parameters in risk stratification and prognosis prediction of patients with acute myocardial infarction, there are no studies conducted in patients with various primary myocardial diseases, thus, this could represent a valuable research direction. Moreover, the ability of fast-SENC to deploy LV wringing and functional dynamic geometry parameters represents another uncharted territory.As for routine clinical applicability, things are still in their infancy. FT-CMR might become a promising option in daily medical practice because it uses standard cine-CMR acquisitions. Additionally, semi-automated or automated software might aid the evaluation. Furthermore, fast-SENC is another promising technique that might significantly reduce the acquisition time for CMR examinations. Nonetheless, due to great disparities in results, which depend on the method of acquisition and data processing, further studies still need to be conducted.The role of CMR in assessing LV myocardial strain and biomechanics is beginning to take shape. Recent technological advancements in the field of CMR, such as fast-SENC and FT-CMR, are able to ensure increased accuracy in evaluating myocardial strain, LV wringing, and active geometry parameters and, along with these developments, increasing evidence endorses their future clinical ability. Even though things are just at the beginning, few yet important studies have shown the tremendous potential which lies behind LV strain and biomechanics.


Echocardiographic right ventricular pulmonary artery coupling (RVPAC) has been shown to be a valid non-invasive and alternative measurement method to assess the predicted outcomes in PAH patients. The aim of this study was to study the effect and clinical correlates of initial ambrisentan plus PDE5i combination therapy on RVPAC in patients with severe PAH.p < 0.001), TAPSE/PASP , S’/PASP , and RVSV/RVESV . Functional status indices [World Health Organization functional classifications (WHO-FC) and 6 min walk distance (6MWD) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels] showed significant improvements. Right heart catheterization (RHC) evaluations for hemodynamic measurements between baseline and the 6–12 month follow-up were sPAP , mPAP  and TPVR . Simultaneously, significant associations between RVPAC ratios and NT-proBNP levels and WHO-FC and 6MWD were observed.We retrospectively studied and analyzed comprehensive clinical data, hemodynamics, and echocardiography in 27 patients with severe PAH before and after 6 months of initial combination therapy. Compared with the baseline, significant improvements in RVPAC ratios were observed, including RVFAC/PASP (0.31 ± 0.10 vs. 0.44 ± 0.15%/mmHg, Ambrisentan plus PDE-5i combination therapy resulted in a significant improvement in RVPAC in severe PAH. Importantly, RVPAC parameters correlated with known prognostic markers of PAH. Pulmonary arterial hypertension (PAH) is a severe clinical syndrome characterized by increasing pulmonary vascular resistance resulting in chronic pressure overload of the right ventricle (RV) and ultimately leading to right heart failure and death , 2.The treatment goal in PAH patients is to achieve good exercise capacity, reduce the RV afterload, keep the patient in WHO-FC II and maintain low mortality rates whenever possible . CurrentThe main prognostic factor of symptoms and outcome in PAH is related to RV function , 5. HoweEchocardiography is a non-invasive ultrasound technique and provides RV function parameters such as tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), tricuspid annular peak systolic tissue Doppler velocity (TASV or S’) and pulmonary artery systolic pressure (PASP) for estimating hemodynamic characteristics or improving RV function in patients with PAH , 9. ReceOur study aims to (1) determine changes in RV function and RVPAC in response to combination therapy with initial ambrisentan plus PDE-5i in patients with severe PAH and (2) evaluate the relationship between RVPAC and clinical parameters.A retrospective study was conducted in treatment-naive patients and their medical records from June 2019 to February 2022 were collected and reviewed at the First Affiliated Hospital of Guangxi Medical University. The patients’ diagnoses were confirmed by RHC, and confirmed by criteria such as a mean pulmonary artery pressure (mPAP) > 25 mmHg, a pulmonary vascular resistance (PVR) > 5 Wood Units (WU), and pulmonary arterial wedge pressure (PAWP) or left ventricular end diastolic pressure of < 15 mmHg . Based oThe following were exclusion criteria: (1) total lung capacity of pulmonary function test was lower than the 60% estimated value; (2) suffering from interstitial lung disease, pulmonary hypertension due to lung diseases or chronic thromboembolic disease; (3) pulmonary hypertension due to left heart disease, including left ventricular systolic or diastolic dysfunction, valvular disease (moderate to severe stenosis or insufficiency confirmed by echocardiography), cardiomyopathies; (4) pulmonary valve or pulmonary arterial stenosis; and (5) autonomic hypotension, severe hepatic and renal impairment.Patients who fulfilled the above criteria and had PAH confirmed by RHC but who had not yet received PAH-specific therapy were enrolled.At the baseline, patient demographics, clinical status and treatment strategies were collected by review of electronic medical records. Heart function was assessed by World Health Organization functional classifications (WHO-FC). A 6 min walk distance (6MWD) was performed according to American Thoracic Society guidelines .Biochemical markers were obtained, and the level of plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) was measured by an enzyme-linked immunosorbent assay using a COBAS 6000 E601 immunoassay analyzer and an Elecsys proBNP II reagent kit .Right heart catheterization was performed using a balloon wedge catheter through the femoral vein or internal jugular vein by standard methods at the first diagnosis of PAH . At the Transthoracic echocardiography was performed on all patients with an available echocardiographic Philips EPIC 7C , and 3DE RV data were digitally analyzed using an advanced data quality quantification system . All parameters were performed both at baseline and after 6 months of combination therapy in patients with severe PAH according to the recommendations for echocardiographic assessment of the right heart by the American Society of Echocardiography chamber guidelines , 20.2 + RAP]. Right atrial pressure was estimated through the inferior vena cava (IVC) size and variability with respiration. RAP is equal to 3 mmHg when the IVC size ≤ 2.1 cm and variability with respiration (> 50% diameter change with inspiration), equal to 8 mmHg when the IVC size > 2.1 cm and variability with respiration (> 50% diameter change with inspiration), and equal to 15 mmHg when the IVC size > 2.1 cm and variability with respiration (< 50% diameter change with inspiration), according to the guidelines idelines .The 3D data were transferred and analyzed using an advanced data quality quantification system  to automatically generate RV volumes and functional indices. Specifically, there were acquired in 3 steps. First, the RV basal short-axis and apical two- and four-chamber views were extracted by an advanced data quality quantification system equipped with 3D viewer software, and the software initially identified RV long-axis landmarks in end-diastole in the apical two- and four-chamber views. Next, the tricuspid valve annulus hinge points and the RV endocardial surfaces were automatically defined and tracked throughout the cardiac cycle (inclusion of papillary muscles and trabeculae in the cavity volume). The automatic tracings were manually adjusted if correction was needed. Finally, the RV volume–time curve was automatically constructed, and RV volumes and functional indices were obtained, including 3D RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV), and RV ejection fraction (RVEF) was calculated using the standard formula: RVEF = (RVEDV-RVESV)/RVEDV . RV fracThese measurements were performed at baseline and after 6 to 12 months of combination therapy.Intraobserver and interobserver variability of the newer measures of RV volume and function assessment were evaluated in 10 randomly selected patients by 2 different investigators. For variability analysis, similar views were used but not necessarily the same beat, each blinded to the results obtained by the other. For intraobserver variability, RV measurements were repeated by the same investigator 6 months later. Reproducibility of the RV measurements was assessed using intraclass correlation coefficients. An intraclass correlation coefficient > 0.9 was considered to represent a high degree of reliability of the strain measurements.RV systolic function was evaluated using RVFAC, S’, TAPSE and RVEF. RV diastolic function was evaluated by the Doppler velocity of the transtricuspid flow (E), lateral tricuspid annular diastolic tissue Doppler velocity (E’) and tricuspid annular E/E’ ratio. The TAPSE/PASP, RVFAC/PASP, RVSV/RVESV and S’/PASP ratios were considered indices of RVPAC –16.t-test, chi-square test, and Wilcoxon signed rank tests were used in patients for measurements at 2 time points. RV volumes adjusted for body surface area (BSA). Correlations between RVPAC indices and NT-proBNP, 6MWD, WHO FC were evaluated by the Spearman rank correlation coefficient or Pearson correlation coefficient. For all tests, a p value less than 0.05 was considered statistically significant.Statistical analyses were performed utilizing SPSS statistical software . Normal and non-normal distributions were determined using the Shapiro–Wilk test and visual analysis . Continuous variables are presented as the mean ± standard deviation or median and interquartile range , and categorical variables are expressed as numbers and percentages. NT-proBNP values were log-transformed for analyses. The paired Student’s n = 15, 55%), congenital heart disease-associated PAH  and systemic lupus erythematosus-associated PAH . During the follow-up period, 21 patients were treated with ambrisentan plus tadalafil, and 6 patients were treated with ambrisentan plus sildenafil. In patients who had WHO FC IV at baseline, there were 4 patients treated with ambrisentan and PDE5i for intermediate risk  who were provided with comprehensive data in this study, including idiopathic PAH (p < 0.001). Simultaneously, a statistically significant difference was observed in the 6MWD   reached WHO-FC I or II . NT-proB= 0.004) .p < 0.001, p = 0.002, p = 0.001, respectively). We did not observe any significant changes in CI (p = 0.110). We observed a baseline median cardiac index of 2.5 L/min/m2, which was indicative of RV dysfunction. At the same time, we did not observe any significant changes in mRAP .The effects of combination therapy on hemodynamics are presented in p < 0.001), TAPSE (p < 0.001), RVEF (p < 0.001), and RVFAC (p < 0.001).Routine RV echocardiographic parameters differenced with respect to ambrisentan plus PDE-5i combination therapy are summarized in p = 0.664) and remained impaired. There was a trend that showed a decrease in RVEDV, whereas RVSV was unchanged after treatment; RVESV significantly decreased. After adjusting for BSA, RVEDVi significantly decreased. At the same time, an RV echocardiography performed at 6 months revealed slightly significant reduction in TRV (p = 0.021) and estimated PASP (p = 0.022) but not in tricuspid regurgitation (p = 0.166).RV diastolic function that assessed by the tricuspid annular E/E’ ratio was not different compared to the baseline  were significantly increased. This indicates that combination therapy may result in significant improvements in RV function and decreases in RVPAC for patients with severe PAH.In this study, we looked for RVPAC changes induced by ambrisentan plus PDE-5i combination therapy . All RVPp = 0.008, p = 0.037, respectively). The rest of measures had no significant correlation with the baseline functional parameters.The correlations between 6MWD, NT-proBNP levels, WHO-FC and RVPAC parameters were showed in r = −0.560; p = 0.003), but had no significant correlation with the TAPSE/PASP, RVFAC/PASP, S’/PASP ratios. WHO-FC was significantly negatively correlated with the TAPSE/PASP, RVFAC/PASP, S’/PASP ratios , but had no significant correlation with SV/ESV ratio. The 6MWD was significantly positively correlated with the TAPSE/PASP, RVFAC/PASP, S’/PASP ratio , but had no significant correlation with the SV/ESV ratio.After treatment, NT-proBNP levels still had a significantly negative correlation with the SV/ESV ratio , and RVSV of 71 mL (59–95), which implied that they were already in an RV-PA uncoupling state. Compared with Gerges et al.  during RHC was only performed at the first diagnosis  in our study. At follow-up measurements, RHC was performed using more economical MPA2 angiographic catheter under fluoroscopic guidance, in 23 patients. and it is different to further analyze the relationship between hemodynamic Ees/Ea and echocardiographic RVPAC. Then, a mix of therapies dose showed in the study. Finally, long-term follow-up was not conducted, however, large-scale, long-term, multicenter prospective studies are needed or confirmation.In conclusion, ambrisentan plus PDE-5i combination therapy resulted in a significant improvement in RV systolic function and RVPAC in patients with severe PAH. These findings provide insight into the hemodynamic and RV effects of ambrisentan plus PDE-5i combination therapy. More importantly, the RVPAC correlated with known prognostic markers of PAH. RVPAC may be an accurate non-invasive and sensitive marker of RV function and clinical improvement in response to combination therapy. Considering multiple factors such as a small number of patients, the conclusion is guarded. Therefore, future prospective studies are required to determine whether or how long combination therapy optimizes RV reverse remodeling and to evaluate treatment outcomes based on a long-term follow-up patients of severe PAH to provide further insights into clinical practice.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Ethics Committee of First Affiliated Hospital of Guangxi Medical University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.W-FL: conception, methodology, data curation, formal analysis, writing-original draft, and writing-review and editing. YD: conceptualization, methodology, design, and writing-review and editing. BW, KH, PD, S-SX, and D-DW: data curation. All authors have read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Endogenous thrombin potential (ETP) was measured at baseline, 1 month and 6 months. Cardiovascular magnetic resonance imaging was performed at baseline and 6 months post-MI. Outcomes studied were an increase in scar change, which was defined as an increase in left ventricular infarct size of any magnitude detected by late gadolinium enhancement, adverse LV remodeling, defined as dilatation (increase) of left ventricular end-diastolic volume (LVEDV) by more than 20% and an increase in left ventricular ejection fraction (LVEF). The mean age was 55.19 ± 8.25 years and 91.2% were men. The baseline ETP was similar in the PPCI and pharmaco-invasive groups . Each 10-unit increase in baseline ETP was associated with a larger scar size . Baseline ETP was not associated with adverse LV remodeling or an increase in LVEF. There was no difference in scar size or adverse LV remodeling among patients undergoing PPCI vs. pharmaco-invasive management or patients receiving ticagrelor vs. clopidogrel. Enhanced thrombin generation after STEMI is associated with a subsequent increase in myocardial scarring but not LV dilatation or an increase in LVEF at 6 months post-MI.Acute myocardial infarction (AMI) is associated with heightened thrombin generation. There are limited data relating to thrombin generation and left ventricular (LV) scarring and LV dilatation in post-MI LV remodeling. We studied 113 patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary percutaneous coronary intervention (PPCI) ( Ischemic heart disease is a frequent cause of death globally . MyocardThrombin has been implicated in post-MI scar formation and ventricular and plays an important role in post-MI pathophysiology. Thrombin participates in platelet aggregation and activates cells through its receptors leading to changes in inflammation, chemotaxis, cell growth, ventricular remodeling and myocyte contraction . IntensiThe primary goal of STEMI treatment with contemporary goal-directed medical therapy is to limit infarct size and salvage ischemic myocardium, thereby preventing adverse LV remodeling which potentially leads to heart failure and cardiovascular death ,16. TherTo investigate the feasibility of thrombin inhibition as a means of reducing myocardial infarct scar size and adverse LV remodeling, we performed a prospective sequential cardiovascular magnetic resonance (CMR) study to examine the association between thrombin generation at baseline and 1 month and the imaging endpoints of myocardial scar size, adverse ventricular remodeling, and an increase in left ventricular ejection fraction (LVEF) at 6 months after STEMI. CMR end-points have been previously shown to be associated with adverse clinical outcomes . We hypoA total of 113 patients were recruited . Over 90p = 0.017). The median troponin levels were also lower in those who had PPCI than in those who had a pharmacoinvasive strategy (Troponin I p < 0.001 and Troponin T p = 0.001). There were no significant differences in lipid profiles or HbA1c levels, nor was there any difference between the biomarkers NT-ProBNP and GDF15. Although there is a theoretical effect of thrombolysis on ETP levels  study; the TIRAMI sub-study as 2013/00248-AMD0002 and the Sarawak General Hospital Heart Centre, Malaysia Medical Research and Ethics Committee NMRR_14-1165-22331(IIR)].In this cohort of patients with STEMI, a higher ETP at baseline was associated with an increase in LV scar size but not adverse ventricular remodeling (dilatation) or an increase in LVEF over 6 months. These associations were consistent regardless of whether patients received upfront PPCI or pharmacoinvasive management. We further observed an association between current cigarette smoking and a decrease in LV scar size, a finding that is consistent with other studies suggesting a protective effect of cigarette smoking on infarct size . InteresOur study provides mechanistic insight into how ETP correlates with post-MI myocardial scarring. There is potential in the strategy of suppressing thrombin generation with anticoagulation, and this may improve clinical outcomes by leading to a reduction in myocardial scar size. In the heart failure population as in the trial COMMANDER-HF, the scar would have already been formed and thrombin suppression may be too little too late in the disease spectrum to prevent adverse cardiovascular outcomes. The use of thrombin-inhibitors may be a reasonable strategy given that there was no increase in bleeding with the use of low-dose rivaroxaban as compared to aspirin in the GEMINI-ACS-1 trial . PrelimiAlthough the PPCI subgroup had a significant decrease in the levels of ETP compared to the pharmacoinvasive group over a 6-month period, which suggests that PPCI is preferred in reducing thrombin generation and subsequent scarring of the myocardium as compared to a pharmacoinvasive strategy, we actually found that there was a similar infarct size at 6 months regardless of whether patients underwent a PPCI or pharmacoinvasive strategy. We did not find any effect of thrombolysis on the effect of scar size on adjusted analysis, but it might be worth exploring the differences in antiplatelet strategies in post-PCI and post-thrombolysis patients and if thrombin suppression leads to different outcomes in these patients. Sonin et al. studied the use of a PAR-1 inhibitor by SCH 79797 in a rat model of ischemia-reperfusion injury. They found that PAR-1 inhibition attenuated adverse LV remodeling, together with a non-significant reduction in scar size. Direct thrombin inhibitors have been demonstrated to prevent left atrial remodeling in a murine model of heart failure . AdditioThe choice of antiplatelet medications in our study population deserves mention. We analyzed the effect of the use of clopidogrel vs. ticagrelor in our regression model. The PLATO trial showed that at 12 months, the death rate from myocardial infarction, vascular causes or stroke was reduced in patients randomized to ticagrelor as compared to clopidogrel . We expeCurrent smoking status was significantly associated with reduced odds of myocardial scarring. The ‘smoker paradox’ has previously been described, where smokers were found to have better cardiovascular outcomes. A study in ST-segment elevation myocardial infarction patients who underwent primary percutaneous coronary intervention showed a lower adjusted risk of in-hospital mortality in smokers . HoweverOur study has several limitations. This was an observational study and as such we could only determine association but not causality in the relation between heightened baseline thrombin generation and subsequent myocardial scar size. Enrolling both PPCI and pharmacoinvasive STEMI patients meant that the sample size for each subgroup was reduced; however, we decided that it was necessary to enroll both subgroups of STEMI patients to enable better generalizability of our study results as a large proportion of patients globally still receive fibrinolytic treatment as the initial reperfusion modality . A majorA higher ETP at baseline was associated with an increased myocardial scar size but not LV dilatation or a change in LVEF over 6 months, regardless of a PPCI or pharmaco-invasive strategy. These data suggest that a clinical trial of dual pathway inhibition in the STEMI population may be warranted to reduce myocardial scar size among patients with enhanced thrombin generation parameters.


The development of various antitumor drugs has significantly improved the survival of patients with cancer. Many first-line chemotherapy drugs are cytotoxic and the cardiotoxicity is one of the most significant effects that could leads to poor prognosis and decreased survival rate. Cancer treatment include traditional anthracycline drugs, as well as some new targeted drugs such as trastuzumab and ICIs. These drugs may directly or indirectly cause cardiovascular injury through different mechanisms, and lead to increasing the risk of cardiovascular disease or accelerating the development of cardiovascular disease. Cardiotoxicity is clinically manifested by arrhythmia, decreased cardiac function, or even sudden death. The cardiotoxicity caused by traditional chemotherapy drugs such as anthracyclines are significantly known. The cardiotoxicity of some new antitumor drugs such like immune checkpoint inhibitors (ICIs) is also relatively clear and requiring further observation and verification. This review is focused on major three drugs with relatively high incidence of cardiotoxicity and poor prognosis and intended to provide an update on the clinical complications and outcomes of these drugs, and we innovatively summarize the monitoring status of survivors using these drugs and discuss the biomarkers and non-invasive imaging features to identify early cardiotoxicity. Finally, we summarize the prevention that decreasing antitumor drugs-induced cardiotoxicity. Antitumor drugs are essential for cancer treatment. These drugs, especially various chemotherapy and immune checkpoint inhibitors (ICIs), have been rapidly developed and used extensively, resulting in the significant increase in the survival rate of patients with cancer. However, how to improve the 5-year survival rate and quality of long-term life of these patients after chemotherapy is a huge challenge that clinicians need to face in the long-term treatment/remission cycle.Cardiotoxicity is served as one of the main factors that affected the quality of life and prognosis of cancer patients . DiffereCardiotoxic complications are the main cause of mortality, and childhood cancer survivors have higher risk of cardiotoxicity . CompareIn this manuscript, we will review the clinical complications and outcomes of several traditional chemotherapy agents and newer targeted cancer therapies that may cause high incidence of cardiotoxicity and poor prognosis. We innovatively summarize the monitoring status of survivors using these drugs and discuss the biomarkers and non-invasive imaging features to identify early cardiotoxicity. Finally, we will summarize the prevention that decreasing antitumor drugs-induced cardiotoxicity.Anthracyclines are one of the most widely used antitumor drugs. Approximately 1 million patients with cancer undergo anthracycline treatment each year. Generally, it is used clinically in many blood system and solid malignant tumors , 8. Anth2, epirubicin ≥ 600 mg/m2) or the use of low-dose anthracyclines (doxorubicin ≤ 250 mg/m2 and epirubicin ≤ 600 mg/m2) accompanied with smoking, hypertension, diabetes, obesity, age over 60 years old, and/or other risk factors  wall thinning, LV diameter increase, and subsequent LV wall stress increase, which is similar to dilated cardiomyopathy . Anthrac2 , 12. Witis lower . In a pr50 mg/m2 . But in hildhood . Therefo2/dose per day; four doses in total) after two cycles of remission induction. On day 3 of the second intensive treatment phase (the phase containing mitoxantrone), the patient developed febrile tachycardia and high oxygen demand. Echocardiogram showed that the LV was enlarged. Compared with the cardiac function before chemotherapy , the LV function was moderately to severely decreased   was an important advance in the field of cancer therapy in the past decade. The anti-CTLA-4 antibody ipilimumab was the first ICI approved by the US Food and Drug Administration (FDA). Subsequently, pembrolizumab, durvalumab, and cemiplimab-rwlc have been approved for clinical treatment . ICI exhFor cardiotoxicity, some research reported the incidence of cardiac IRAEs is low (<1%), but the prognosis extremely poor especially life-threatening fulminant myocarditis, and the median time from the first exposure of ICI to the onset of myocarditis is 30 days –24. In aCurrently, breast cancer is the most common malignancy among women worldwide, with over 2 million new cases diagnosed in 2018 . Human eA study focusing on HER2 overexpression proved that trastuzumab combination therapy is effective and that its relative risk of death and the recurrence rate were reduced by 20 and 51%, respectively . HoweverCardiotoxicity also been reported when trastuzumab is used in combination with other drugs even without anthracycline. A recent study compared two types of neoadjuvant chemotherapy for HER2 breast cancer and showed that the incidence of cardiac events was 7.7% among patients who received trastuzumab plus docetaxel and carboplatin (TCH) after 9 years’ follow-up. During chemotherapy or up to 1 year after chemotherapy, 4.6% patients in the TCH group developed early-stage CHF .In animal experiments, Yi et al. revealed that trastuzumab combined irradiation caused more cardiotoxicity than irradiation or trastuzumab alone, which suggested that the concurrent management of trastuzumab and radiotherapy should be carefully made in clinical practice, and more attention is needed on cardiac safety  Figure .The diagnosis of cardiotoxicity in patients undergoing cancer treatment before having clinical manifestations has a very positive effect on the prognosis. Therefore, patients with cancer undergoing chemotherapy are strongly recommended to undergo regular or even lifelong cardiac function monitoring. Cardiotoxicity monitoring commonly includes serum biological markers, ECG, echocardiography, cardiac magnetic resonance (CMR) and other methods such as endomyocardial biopsy (EMB) and cytokine measurements. Each of these detection methods has its own advantages and disadvantages. The disadvantages and the corresponding suggestions for the common methods for cardiotoxicity monitoring are shown in the Serum biomarkers are important for the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients treated with potentially cardiotoxic drugs. The increase of cardiac biomarkers, especially cardiac troponin (cTn) and natriuretic peptide (NPs), can be used to guide the initiate of cardioprotective therapy during cancer treatment and monitor the responses of these protective therapy .Antitumor therapy is often accompanied with troponin increasing, and patients with elevated troponin levels have a higher risk of left ventricular dysfunction . In a stIn addition, the elevation of BNP and NTroBNP during anthracycline treatment is also associated with the reduction of LVEF and poor prognosis . A cohorA consensus from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group suggested that cardiac troponins screening should be performed in the first 12 weeks of ICI treatment . The assElectrocardiogram, as a routine evaluation method, can reflect the electrophysiological activity of the heart in time before, during and after tumor treatment. Tumor drugs may induce arrhythmias through a variety of ways . AlthougPremature ventricular beats are the most common type of arrhythmia in patients treated with anthracyclines, with ventricular tachycardia occurring in approximately 73.9% of patients . KilickaClinically, the most common parameters include EF, SF, LV wall stress, LV mass, rate of shortening of heart rhythm correction, LV thickness-to-size ratio, and diastolic function in the echocardiographic examination . In receAlthough Echo is considered a routine test for cancer patients to monitor the cardiotoxicity, recent studies have shown that the LVEF measured by CMR has the highest repeatability compared to the LVEF measured by two-dimensional echocardiography  in patients with cardiomyotoxicity due to cancer therapy , 67. TheMyocardial strain could be an alternative more sensitive imaging biomarkers than LVEF to earlier diagnosis and treatment of cardiotoxicity. The reduction in global longitudinal and circumferential strain assessed by CMR tissue-feature tracing is associated with subclinical decline in LVEF in cancer patients . The gloT1 mapping and T2 mapping technology on CMR is a promising non-invasive tool that can quantify myocardial tissue changes via changes in longitudinal and transverse relaxation, allowing for the early detection of cardiotoxicity . T2 mappQuantitative T1 imaging can be used to calculate the myocardial extracellular volume fraction (ECV), a measure of microscopic myocardial remodeling that has been associated with underlying diffuse fibrosis . In receMyocardial fibrosis can be detected non-invasively by late gadolinium enhancement (LGE) with CMR, which is the priority imaging test for the diagnosis and risk prediction in myocarditis of other etiologies –81. But Cardiac magnetic resonance are helpful in individuals whose echocardiographic techniques are not feasible or whose results are suboptimal, and provide more information about myocardial perfusion. However, the cost of CMR is extremely expensive for a population-based screening, and comprehensive multi-parametric CMR tissue studies are currently unavailable . In receCytokines, inflammatory factors, and endocardial biopsies can also be used to monitor myocardial toxicity. The cytokine’s sensitivity to inflammation makes it useful for monitoring cardiotoxicity. An animal experiment showed that the cardiac tissue levels of TNF-α, IL-6, and IL-1β in the DOX-treated group were significantly increased as compared to the normal group rats . Ahmed eMyocarditis is one of the important manifestations of ICI related cardiotoxicity. Recently Vincenzo et al. found that the expression of IL-6 and IL-1 in breast cancer cells and cardiomyocytes exposed to ipilimumab significantly increased when in high glucose state, suggesting the protective role of low glucose in immune-suppression and cardiotoxicity .Endomyocardial biopsy is available to detect tissue damage, primarily for rejection monitoring after cardiac transplantation and also have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders , but the2 or epirubicin cumulative doses up to 540 mg/m2. Ganatra et al. observed clinical outcomes in five patients with preexisting asymptomatic left ventricular systolic dysfunction who required chemotherapy with anthracycline, in combination with off-label treatment with Dexrazoxane 30 min before each anthracycline dose. All five patients treated with Dex successfully completed chemotherapy as planned, with mean LVEF decreasing from 39% at baseline to 34% after chemotherapy, without symptomatic heart failure or elevated biomarkers (cardiac troponin I or brain natriuretic peptide). In three patients who were not treated with Dexrazoxane, the LVEF decreased from 42.5% at baseline to 18% after treatment. All patients developed symptomatic heart failure requiring hospitalization and diuretic therapy, and two died of cardiogenic shock and multiple organ failure. Therefore, this study suggested that Dex can reduce the cardiotoxicity induced by anthracyclines in adults with existing cardiomyopathy and tumors (2 (Dexrazoxane (DEX) is an iron chelating agent that minimizes cardiotoxicity by limiting the production and accumulation of ROS in myocardium and preventing the interaction between antitumor drugs and topoisomerase II . Dex is d tumors . Lisa etd tumors . Dewildeumors  and the early use of corticosteroids are associated with improved cardiac prognosis in ICI-related myocarditis. This previous study supported that the initial dose of corticosteroids is inversely related to the occurrence of major adverse cardiovascular events (MACE), the rate of MACE are 61.9, 54.6, and 22.0% respectively in low, medium and high dose initially . PatientThe specific mechanism of trastuzumab related cardiotoxicity remains unclear , 100. ThOncological cardiology is an emerging discipline involving oncology, cardiovascular, imaging, laboratory, and other fields. With the continuous in-depth research on antitumor drugs, various chemotherapeutic and new targeted drugs are being used widely in clinical, and their adverse effects cannot be ignored. Such adverse events may be the major causes of death. Cardiotoxicity based on chemotherapy drugs and ICIs is mainly manifested as various types of cardiac dysfunction, HF and myocarditis and may be associated with high morbidity and mortality. Therefore, early detection of cardiotoxicity facilitated by these monitor methods especially the advanced multimodality imaging techniques summarized in this review will permit intervention at an earlier stage, which is crucial for the improvement of patient’s quality of life and decrease in mortality risk. The future development of oncological cardiology may require more attention to high-risk populations, cardiac function monitoring, and preventive and therapeutic administration. Furthermore, the mechanism of cardiotoxicity caused by various traditional chemotherapy agents and newer targeted cancer therapies should be researched further to determine ways on how to protect patients with cancer from cardiotoxicity.WH and RX wrote the manuscript. BZ and CL provided a detailed guidance throughout the manuscript. HX, XG, and YG responsibility for the integrity of the work as a whole from inception to published manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


LBBP showed comparable pacing parameters to RVAP or RVSP and was significantly better than HBP, with maintained cardiac function. TS‐12‐SD was significantly improved in LBBP (41.80 ± 20.97 ms) than RVAP  and RVSP  but similar to HBP  or RVSPring . Among these pacing strategies, negative values of interventricular mechanical delay (IVMD) were only identified in LBBP (−19.25 ± 18.43 ms), significantly different from RVAP (35.00 ± 30.72 ms), RVSP (22.85 ± 22.05 ms), HBP (5.20 ± 18.64 ms), and RVSPring . Using Pearson's analysis, Sti‐LVAT was positively correlated with QRS duration, IVMD, TS‐12‐SD, LVEDV, and LVESV, while a negative relationship could be observed for left ventricular ejection fraction.Similar to HBP (114.84 ± 18.67 ms), narrower paced QRSd was found in LBBP (116.15 ± 11.60 ms) as compared to RVSPHis‐Purkinje conduction system pacing (HPCSP) achieved better electrical and mechanical synchrony than conventional RV pacing. For interventricular synchrony, only LBBP initiated earlier LV activation than RV, in accordance with the right bundle branch block (RBBB) pattern of paced QRS during LBBP. Sti‐LVAT might be a good parameter correlating with LV systolic function and mechanical synchrony. AVBatrioventricular blockEPelectrophysiologyHBPHis bundle pacingHPCSPHis‐Purkinje conduction system pacingIVCDintraventricular conduction defectIVMDinterventricular mechanical delayLBBPleft bundle branch pacingLVEFleft ventricular ejection fractionLVEDVleft ventricular end‐diastolic volumeLVESVleft ventricular end‐systolic volumeRBBBright bundle branch blockRVAPright ventricular apex pacingRVPright ventricular pacingRVSPright ventricular septum pacingringRVSPRVSP during unipolar pacing from the ring electrode of LBBP leadSti‐LVATthe stimulus to left ventricular activation timeTAPSEtricuspid annular plane systolic excursionTS‐12‐SDstandard deviation of the time‐to‐peak myocardial sustained velocity of 12 left ventricular segments1For decades, right ventricular pacing (RVP) has been established as a conventional pacing technique indicated for symptomatic bradycardia for its pacing efficacy and safety. However, RVP is obviously not a physiological pacing strategy and it could lead to interventricular and intraventricular electrical desynchrony, which might result in atrial fibrillation and heart failure,His‐Purkinje conduction system pacing (HPCSP), His bundle pacing (HBP), and left bundle branch pacing (LBBP), have emerged as two physiological conduction system pacing strategies and have been demonstrated to achieve narrower QRS duration and better mechanical synchrony than RVP.22.1Twenty patients with complete AVB indicated for dual‐chamber pacemaker implantation were included in the study. Exclusion criteria included persistent atrial fibrillation, escape beat of intraventricular conduction defect (IVCD) morphology, and left ventricular ejection fraction (LVEF) < 50%. Written informed consent was obtained from all of the participants and the study was approved by the Institutional Review Board of Zhongshan Hospital, Fudan University, Shanghai, China.2.2ring) were successively performed in each patient , right ventricular septum pacing (RVSP), HBP, LBBP, and unipolar pacing from the ring electrode of LBBP lead  Figure , defined2.4During follow‐up , QRS durations and echocardiographic parameters, including LVEF, LVEDV, and LVESV were collected and compared. The procedure‐related complications, including lead dislodgement, perforation, device, or lead infection, pericardial effusion, and thromboembolism were also collected.2.5t‐test was used to compare the difference between baseline and 6‐month follow‐up in each group. Analysis of variance test was used to perform comparison among more than two groups and was followed by the least significant difference test for multiple comparisons. Categorical variables were presented as numbers (percentages) by using Pearson's X² test or Fisher's exact test. The correlations between electrophysiological characteristics and echocardiographic parameters were performed by Pearson's analysis. All analyses were performed by SPSS version 22.0  and a two‐sided p < .05 was considered statistically significant.Continuous variables were expressed as mean ± SD and paired Student's 33.1p < .01). Threshold in LBBP (0.73 ± 0.24 V) was similar to RVAP  and RVSP  but significantly lower than RVSPring . For R‐wave amplitude, there was no difference between LBBP (9.43 ± 4.14 mV) and RVAP  or RVSP . With regard to impedance, LBBP (629.61 ± 155.58 Ω) is relatively lower than RVAP  but similar to RVSP . Moreover, higher impedance was demonstrated in LBBP when compared to RVSPring . As for LBBP, LBB potential was recorded in 15 cases (75%) and 16 cases (80%) achieved selective LBBP during the procedure.A total of 20 patients  with complete AVB were enrolled and their baseline characteristics are shown in Table 3.2p = .001), RVAP , as well as RVSPring  resulted in a remarked increase in QRS duration compared to the baseline (118.75 ± 24.63 ms) . Concerning Sti‐LVAT, LBBP (65.47 ± 7.98 ms) showed the shortest Sti‐LVAT compared with RVSP , RVAP , HBP , and RVSPring   Figure . QRS dur) Figure .p = .029) and RVA (p = .004). Significant negative means of IVMD was demonstrated in LBBP (−19.25 ± 18.43) than RVSP (22.85 ± 22.05 ms), RVAP (35.00 ± 30.72 ms), HBP (5.20 ± 18.64 ms), and RVSPring (16.00 ± 26.76 ms)   and RVA (p < .001).Among all the different pacing sites, there was no significant difference in TS‐12‐SD as compared to baseline (55.20 ± 27.11 ms) while a decreasing trend could be seen during HBP (51.50 ± 25.66 ms) and LBBP (41.80 ± 20.97 ms) Figure . Whereas) Figure . IVMD du3.3p = .016), RVAP , and RVSPring  (Table p = .004), RVAP , and RVSPring  compared with baseline (20.33 ± 2.54 mm) while HBP  and LBBP  remained stable.LVEF in HBP (62.71 ± 7.69%) and LBBP (62.93 ± 6.09%) was comparable to baseline (62.12 ± 13.83%) while a significantly decreased LVEF was identified in RVSP  Table . For oth3.4r = 0.612, p < .001), LVEDV , LVESV , TS‐12‐SD , and IVMD , while a negative relationship between Sti‐LVAT and LVEF  was demonstrated . No significant association between Sti‐RVAT and echocardiographic parameters were confirmed, either.Correlations between electrophysiological characteristics and echocardiographic parameters are summarized in Table d Figure . However3.5p = .300) and sensed R‐wave amplitude  during unipolar configuration (Table p = .008) after implantation and it was maintained till 18 months follow‐up  (Table p = .952) nor QRS duration  showed significant difference during follow‐up and none of the complications, including lead dislodgement, perforation, device or lead infection, pericardial effusion, or thromboembolism were reported.Follow‐up echocardiograms were obtained at least 18 months after the initial pacemaker implant in each patient. Stability was maintained in LBBP capture  Table . Neither4The present study directly compared electrophysiological characteristics and echocardiographic parameters at different pacing sites in each patient during the procedure and the main findings were as follows: (1) similar to HBP, LBBP preserved better electrical and LV mechanical synchrony compared with conventional RV pacing (RVAP or RVSP); (2) our research provided the initial evidence of earlier LV electrical activation than RV during LBBP in accordance with interventricular synchrony ; (3) there were significant correlations between Sti‐LVAT and echocardiographic parameters, including LVEDV, LVESV, LVEF, TS‐12‐SD, and IVMD.4.1Paced QRS duration is demonstrated to be narrower in LBBPring, a specific RVSP during unipolar pacing from the ring electrode of LBBP lead. It might be a better pacing site than conventional RVAP or RVSP since the mean QRS duration during RVSPring was significantly decreased than RVAP and the trend was confirmed when comparing with RVSP but no statistical significance was found. Since the length between the tip and the ring of the lead (Mode 3830) was 10.8 mm, the pacing site of RVSPring was still RVS in most cases and might be a little bit deeper than conventional RVSP when the lead screwed deep inside the septum. Hence, the mean QRS duration and sti‐LVAT during RVSPring were significantly increased than LBBP, though they showed a decreased trend than RVAP or RVSP. And the pacing parameters were good as well during RVSPring. Dual cathodal lead might be designed in the future to give an additional pacing option.A novel pacing site of the present study was RVSP4.2ring. It might be attributed to the study population (AVB patients without heart failure) and small‐sample‐sized study design.Better LV mechanical synchrony has been previously confirmed during LBBP than RVSP using SPECT MPI and echocardiogram.ring. IVMD evaluates the mechanical synchrony between LV and RV and is recognized as a predictive factor in CRT response.Furthermore, IVMD was measured and compared in the study and showed a significant difference between LBBP and HBP or RVAP or RVSP or RVSPConcerning our findings of TS‐12‐SD and IVMD, HBP maintained inter and intraventricular synchrony while LBBP preserved LV synchrony with delayed RV activation. Conversely, RVP resulted in earlier RV activation and deteriorated LV synchrony.4.3To maintain satisfied heart function and mechanical synchrony after implantation, it is of significant importance to confirm a simple and reliable electrophysiological value correlated to echocardiographic parameters during pacing. Sti‐LVAT is indicated for the depolarization duration of the LV wall. Hence, a shorter Sti‐LVAT may represent rapid propagation of LV activation leading to synchronous LV contraction. During LBBP, Sti‐LVAT has been reported to be a useful parameter to determine LBB capture according to electrophysiological mapping while QRS duration failed to act as an ideal diagnostic value for LBB capture due to its delayed RV activation.4.4The study focused on the electrical and mechanical synchrony at different pacing sites during the procedure. These findings were acute hemodynamic results. Thus, the long‐term hemodynamic effects of LBBP remain uncertain. In addition, it is a single‐center, self‐controlled observational study, with relatively small sample size. The main study population was AVB with narrow QRS or RBBB and normal LVEF. Consequently, the results of the study could not be generalized to patients with IVCD or heart dysfunction.5HPCSP provided better electrical and mechanical left ventricular synchrony than conventional RVP. While interventricular synchrony during LBBP was significantly different as compared to HBP, RVAP, and RVSP, showing earlier LV activation than RV, which was consistent with the RBBB pattern of paced QRS during LBBP. Sti‐LVAT might be a good electrophysiological parameter correlated to LV systolic function and mechanical synchrony.All authors have read and approved the manuscript. Methodology and manuscript writing: Xueying Chen, Qinchun Jin, Yanan Wang, Xiaolan Zhou. Data collection and pacing perfomance: Yufei Chen, Jingfeng Wang, Shengmei Qin, Jin Bai, Wei Wang, Yixiu Liang. Conceptualization and supervision: Haiyan Chen, Yangang Su, Junbo Ge.The authors declare no conflicts of interest.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.