We review this important article from 2022 with attention to vital considerations for surgeons performing procedures on patients with CIEDs.All surgeons, particularly cardiovascular surgeons, encounter patients with cardiac implantable electronic devices (CIEDs). In 2022, the European Heart Rhythm Association (EHRA), in collaboration with the Heart Rhythm Society (HRS), Latin America Heart Rhythm Society (LAHRS), and the Asia-Pacific Heart Rhythm Society (APHRS), published their consensus statement on the prevention and management of interference due to medical procedures in patients with CIEDs.The EHRA consensus was developed by a panel of 20 authors and representatives from HRS, LAHRS, and APHRS who performed a thorough review of published literature in order to develop a categorized and critically supported consensus document. The EHRA consensus was built upon the well-established practice that CIED patients demand distinct consideration throughout the perioperative period with a “no-one-size-fits-all” approach for the procedural considerations fundamental to each device type. Individual devices and manufacturers have unique properties and programming, which surgeons should understand when treating CIED patients. The EHRA consensus developed measured recommendations with associated color-coded categories. Statements supported by strong scientific evidence and expert agreement (green) should be universally followed. Those with general agreement and moderate supporting evidence (yellow) should be regularly implemented. Finally, procedures or testing that should not be used (red) based on published evidence and expert agreement should be avoided.2 While modern pacemakers have been developed to withstand most normal day-to-day electromagnetic interference, the hospital setting is still associated with an increased risk to these devices and the patients they support. Electromagnetic interference (EMI) affecting these devices may result in pacing inhibition, cross-chamber pacing, alteration of rate responses, asynchronous pacing, inappropriate mode switching, modification of pacing thresholds, pacemaker-induced tachycardia and/or permanent effects on power on reset and backup mode.1The development of the pacemaker in the 1960s had a substantial impact on the interventions available to the cardiac patient. These devices sense aberrations within the electrical activity of the heart and, as a result, send out support signals on demand to induce myocardial contraction. Given the nature of how these devices work, the support they provide is inherently at risk of interference from outside electromagnetic sources, which they may incorrectly attribute as originating from the heart’s conduction system. This interaction has created clinical dilemmas for health care providers, especially with the increasing population of CIED patients.Implantable cardioverter-defibrillators (ICDs) also sense aberrations within the heart’s electrical activity and will shock the heart in order to reset a rhythm that is too fast to support hemodynamic stability. Modern ICDs also have pacemaker functionality. Oversensing caused by EMI can result in inappropriate shocks to the patient, modified pacing function, long–short–long sequence pacing, truncation of pacing output, and/or sudden battery depletion.For patients with low ejection fractions (<35%) and prolonged QRS durations (>150 ms) with left bundle branch block, cardiac resynchronization therapy (CRT) may improve cardiac output and heart failure symptoms. CRT re-establishes the electrical coordination of the left and right ventricular chambers using sophisticated pacemaker algorithms. In addition to transvenous lead sensing and pacing of the right ventricle, a second ventricular lead senses and paces the left ventricle. The left ventricular lead most commonly resides within the distal branch veins of the coronary sinus, but it may also be located on the epicardial surface of the left ventricle. The implanted device may also include an ICD capability.Patients with implantable loop recorders that experience EMI may be subject to artifacts that mimic tachyarrhythmias.1 tissue burns, induced atrial or ventricular fibrillation, or device reprogramming.2 Device interference may be caused by direct contact or by radiated interference. Common sources of interfering electromagnetic fields include electrocautery, radiofrequency ablation (both cardiac and non-cardiac), radiofrequency identification devices, electrical stimulation therapy, and therapeutic diathermy. Electrical cardioversion/defibrillation, electroconvulsive therapy, magnet-utilizing tissue expanders, electromyograms, and lithotripsy have also been documented as sources of interference. Magnetic resonance imaging (MRI) and exposure to therapeutic ionizing radiation  are the most common radiation sources of interference with CIEDs. The hospital setting and surgical procedures expose patients to these frequencies, and it is vital that physicians and other health care clinicians are aware of the steps to mitigate significant negative outcomes.Electromagnetic fields (EMFs) and radiation are known to cause interference with CIEDs and may pose a significant risk to patients who are supported by these devices. Possible effects include direct damage to the leads or devices, oversensing resulting in either lack of therapeutic stimulation or inappropriate pacing/ICD therapy,Perhaps the most important aspect of the perioperative management of the patient with a CIED is collaboration with the cardiologist, specifically the electrophysiologist. Whenever possible, CIED patients should undergo a cardiology evaluation prior to any procedure, especially one with anticipated exposure to device interference. The pre-procedural evaluation should include a thorough work-up of the patient’s device type, model, and manufacturer. A chest X-ray may be required in order to determine details of the device, leads, and placement. A review of the device’s functionality, battery status, program settings, and the patient’s reliance on device interventions needs to be completed to properly plan and progress to the operative phase of the patient’s hospital course. Once the patient’s device status is well understood, the operative details may be assessed to determine the appropriate course of action for safe procedure performance. The approach will vary depending on the device, area of planned treatment, patient positioning, and anticipated exposure to EMI.Intraoperatively, electrocardiographic monitoring is important, particularly if the use of electrocautery is anticipated. Participating clinicians should be attuned to possible EMI and ensure optimized monitor settings for CIED patients. The ability to monitor peripheral pulses is also a necessity for identifying any hemodynamic instability. Defibrillation and grounding pads should be placed >15 cm away from the device to avoid permanent damage in the event backup pacing or defibrillation is required. Defibrillation pads should be positioned in the location that directs the vector of delivered energy away from the CIED, generally in an anterior-to-posterior manner. At least 1  magnet(s) (≥10 G) should be on hand at all times during the procedure. In addition, personnel trained on the specific CIED device need to be available in-house should device reprogramming be required.Electrocautery is the main source of EMI while in the operating room. Though intermittent electrocautery application is recommended, i.e., employing <5-s cautery bursts, surgeons should understand that this does not totally eliminate the risk of ICD shocks. For this reason, if available, the use of bipolar electrocautery and/or ultrasonic scalpels is advised. The EHRA consensus statement highlights that, while previous recommendations have indicated that ICD inactivation may be avoided in patients being treated below the umbilicus if unipolar electrocautery is utilized, unintentional misplacement (return pad too close to device) or utilization of full-body return electrode pads  has resulted in device oversensing. Updated guidance suggests that the iliac crest is a more suitable demarcation, with the return electrode placed on the thigh, and the EHRA consensus statement thus references this rather than the umbilicus. Following this guidance, magnet application and/or device reprogramming, in general, is not required for procedures performed below the iliac crest. The consensus statement, however, does indicate that, while not mandatory, it may simplify the protocol to universally plan on magnet application for all ICD patients regardless of treatment location. Device reprogramming prior to any procedure with the slightest risk of EMI is necessary for all pacemaker-dependent ICD patients.. While magnet application results in asynchronous pacing, ideal magnet placement and default magnet mode settings vary depending on manufacturer, with some having only a temporary asynchronous response. The ability for the device to spontaneously reprogram intraoperatively in response to EMI should not be overlooked. Continuous electrocardiogram monitoring is critical throughout the time period in which pacemaker patients have an applied magnet or asynchronous mode set, as there is a risk of ventricular pro-arrhythmia, which may require external defibrillation and transcutaneous pacing. Pacemaker-dependent ICD patients must have their device reprogrammed for the intraoperative period, as pacing mode will not be affected by magnet application. When evaluating cardiac surgical patients, procedures are typically done ≤15 cm from CIED devices, and devices should all be reprogrammed for the procedures’ entirety. This guidance is also applicable in the setting of procedures performed <15 cm away with secure magnet placement impossible due to patient positioning.Optimally, and prior to the patient entering the procedure room, an experienced practitioner should reprogram the device or at least determine whether the procedure and/or device can safely proceed without reprogramming. Industry-employed professionals should not develop treatment strategies. Although reprogramming to the asynchronous mode may be the most common intervention, each device and clinical situation warrants an individualized assessment and modification. Magnet application for pacemakers does not ensure a standardized response and varies by specific device Immediately following any procedure, the CIED needs to be interrogated for any perioperative events and reprogramming. Procedures with EMI involvement must receive a full device follow-up by the electrophysiologist to ensure no physical damage or dysfunction has occurred. Patients should be closely monitored with appropriate interventions immediately available until proper review and reprogramming occurs.To summarize, the safest recommendations include reprogramming the CIED prior to a surgical procedure and continuously monitoring electrocardiography and blood pressure. These management plans help reduce the risk of human error with pad or magnet placement, low awareness of EMI risk, inadequate assessment of pacing dependence, or unsuccessful memorization of multiple variables and flow charts. Clinical decisions regarding perioperative CIED management may be based upon the perception of risk or device dependency, which can only be truly assessed by device interrogation. These assumptions and recommendations also do not include any element of patient or procedure variability. One cannot always predict how a patient will react while under anesthesia or anticipate unexpected surgical events.


Ischemia of the hypertrophied myocardium due to microvascular dysfunction is related to a worse prognosis in hypertrophic cardiomyopathy (HCM). Stress and rest T1 mapping without contrast agents can be used to assess myocardial blood flow. Herein, we evaluated the potential of non-contrast stress T1 mapping in assessing myocardial injury in patients with HCM.Forty-five consecutive subjects (31 HCM patients and 14 control subjects) underwent cardiac magnetic resonance (CMR) at 3T, including cine imaging, T1 mapping at rest and during adenosine triphosphate (ATP) stress, late gadolinium enhancement (LGE), and phase-contrast (PC) cine imaging of coronary sinus flow at rest and during stress to assess coronary flow reserve (CFR). PC cine imaging was performed on 25 subjects (17 patients with HCM and 8 control subjects). Native T1 values at rest and during stress were measured using the 16-segment model, and T1 reactivity was defined as the change in T1 values from rest to stress.ATP stress induced a significant increase in native T1 values in both the HCM and control groups . T1 reactivity in the HCM group was significantly lower than that in the control group . On univariate analysis, T1 reactivity correlated with native T1 values at rest, left ventricular mass index, and CFR. Multiple linear regression analysis demonstrated that only CFR was independently correlated with T1 reactivity . Furthermore, segmental analysis showed decreased T1 reactivity in the hypertrophied myocardium and the non-hypertrophied myocardium with LGE in the HCM group.T1 reactivity was lower in the hypertrophied myocardium and LGE-positive myocardium compared to non-injured myocardium. Non-contrast stress T1 mapping is a promising CMR method for assessing myocardial injury in patients with HCM.Trial registration Retrospectively registered. Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by inappropriate left ventricular hypertrophy . MyocyteCardiac magnetic resonance (CMR) is a useful non-invasive imaging modality for the assessment of cardiac function and myocardial tissue characterization. Late gadolinium enhancement (LGE) can detect myocardial fibrosis, but it is ineffective for evaluating diffuse interstitial fibrosis . T1 mappIt has been reported that adenosine stress and rest T1 mapping may be useful to distinguish between normal and ischemic myocardium in CAD without gadolinium contrast agents , 13. TheIn this study, we sought to evaluate the hypothesis that non-contrast T1 mapping at rest and during adenosine triphosphate (ATP) stress can detect myocardial injury in patients with HCM.We retrospectively enrolled 31 patients with HCM and 14 control subjects who underwent CMR imaging to evaluate suspected CAD between October 2018 and June 2022. In the HCM group, the electrocardiogram of all patients revealed ST-T changes including ST depression or negative T waves. Five patients presented with atypical chest discomfort and the remaining were asymptomatic. None of patients had a history of non-sustained ventricular tachycardia or syncope. HCM was diagnosed according to the JCS/JHFS guideline and was defined as left ventricular wall thickness ≥ 15 mm (in the absence of a family history of HCM), or 13–14 mm (with a family history of HCM) [CMR imaging was performed using a Magnetom Skyra 3T system  with a 60-channel body coil. This included cine images, T1 mapping at rest and during ATP stress, late gadolinium enhancement (LGE), and phase-contrast (PC) cine imaging of coronary sinus flow at rest and during ATP stress to assess the coronary flow reserve (CFR). Patients were instructed not to consume caffeine for 12 h before ATP stress CMR. PC cine imaging was performed on 25 subjects (17 patients with HCM and 8 control subjects). Short-axis images covering the left ventricle (LV) from base to apex and 2-chamber, 3-chamber, and 4-chamber long-axis cine images were acquired with steady-state free precession to evaluate cardiac function and myocardial mass (repetition time (TR): 28.2 ms, echo time (TE): 1.6 ms, flip angle: 60°, field of view (FOV): 360 × 270 mm, acquisition matrix: 224 × 224, slice thickness: 6 mm, number of cardiac cycle phases: 30). T1 mapping at rest was performed on short-axis slices at the base, mid-ventricle, and apex . Left ventricular volume, ejection fraction, and mass were calculated by manual tracing of endocardial and epicardial contours of the end-diastolic and end-systolic short-axis cine images . PerfusiAll data are expressed as a mean ± standard error of the mean. A chi-square analysis was performed to evaluate the association between the collected clinical information. The Mann–Whitney U test was used to compare age, body mass index (BMI), and CMR data between the HCM and control groups. This test was also used to compare native T1 values at rest  and T1 reactivity between LGE-positive and LGE-negative groups and segments. The difference in T1 reactivity between the three groups was calculated using a 1-way analysis of variance with Bonferroni’s post hoc test. The Kruskal–Wallis test was used to compare resting T1 values between the three and four groups and T1 reactivity among the four groups, followed by Dunn’s post hoc test with Bonferroni correction. Univariable and multivariable linear regression analyses were used to evaluate the relationship between T1 reactivity and the clinical and imaging parameters. All variables associated with T1 reactivity (p < 0.2) were included in multivariable linear regression analysis . Area unThe clinical characteristics of the patients are summarized in Table 2 vs. 39.6 ± 1.6 g/m2, p < 0.001). There were no statistically significant differences in systolic and diastolic blood pressures between the HCM and control groups .The CMR data are listed in Table Resting T1 values in the HCM group were significantly higher compared to those in the control group . With regards segmental analysis, segments with LGE showed significantly higher rest T1 values and lower T1 reactivity than those without LGE .CFR was significantly lower in the HCM group compared to the control group . Univariate analysis showed that resting T1 values, LVMI, and CFR were correlated with T1 reactivity. However, there was no significant correlation between T1 reactivity and age, BMI, or LVEF. Multiple linear regression analysis demonstrated that only CFR was independently correlated with T1 reactivity  were significantly higher compared to those in the non-hypertrophied myocardium in the HCM . Resting T1 values in the hypertrophied myocardium without LGE were significantly higher compared to those in the non-hypertrophied myocardium without LGE p = 0.014). There was no statistically significant difference in the rest T1 values between the hypertrophied myocardium with LGE and the non-hypertrophied myocardium with LGE (Fig. . There wThis study showed that patients with HCM had a higher resting T1 values and lower T1 reactivity compared to control subjects, and T1 reactivity was correlated only with CFR measured by PC cine MRI. Additionally, T1 reactivity was significantly lower in the hypertrophied myocardium of the HCM group compared to the non-hypertrophied myocardium of the HCM and control groups. T1 reactivity in the hypertrophied and non-hypertrophied myocardium with LGE was equivalent to that in the hypertrophied myocardium without LGE. To the best of our knowledge, this study is the first to show that T1 reactivity can assess myocardial injury globally and regionally in HCM patients without a gadolinium contrast agent.Stress perfusion imaging with MRI and PET has been reported to be useful for the detection of hemodynamically significant CAD and the determination of invasive revascularization , 24. CFRT1 mapping can be used for myocardial tissue characterization, and patients with HCM showed significantly higher native T1 values and ECV compared to healthy volunteers despite the presence of LGE . FurtherAutopsy in patients with heart failure with preserved ejection fraction revealed that microvascular density was correlated with the severity of myocardial fibrosis . Ma et aThis study has some limitations. First, the sample size was small. Therefore, a larger prospective study is required to confirm these findings. Second, MRCA or CTCA was performed to evaluate CAD in subjects with positive stress perfusion. Patients with significant CAD were excluded, but invasive coronary angiography was not performed. Therefore, the exclusion of significant CAD may have been incomplete in this study. Third, the perfusion defect was assessed visually and the diagnostic accuracy for detecting myocardial perfusion defect by T1 reactivity was moderate. The measurement of myocardial blood flow or myocardial perfusion reserve is warranted in future investigations to examine the comparison between T1 reactivity and myocardial hypoperfusion. Finally, 13.1% of myocardial segments were excluded because of insufficient image quality during ATP stress. The MOLLI sequence used in this study was modified to reduce heart rate sensitivity , 17, butIn conclusion, T1 reactivity was decreased in hypertrophied myocardium and LGE-positive myocardium compared with non-injured myocardium. Our results suggest the potential use of non-contrast stress T1 mapping for evaluating myocardial injury globally and regionally in patients with HCM; however, further studies are needed to elucidate the clinical significance of these findings.


Since the introduction of surgical implantation of conduit for right ventricle-to-pulmonary artery pathway reconstruction, there has been a number of studies on possible factors which might potentially affect conduit longevity, as well as patient’s reintervention-free and overall survival. Still, no definite consensual agreement could be made thus far. We aimed to compare conduit longevity, reintervention-free survival, and overall survival between patients with congenital heart diseases indicated for operations involving right ventricle-to-pulmonary artery pathway reconstruction whose conduits were placed heterotopically to those with orthotopically placed ones.We retrospectively collected data from electronic medical records of Ramathibodi hospital from 1st January 2005 to 31st December 2022. Patients with congenital heart diseases whose operations involved reconstruction of right ventricle-to-pulmonary artery continuity were included. Patients whose medical record data were significantly missing were excluded. Demographic data, operative, and postoperative details were collected and reviewed.There were 67 patients included in our study, with 25 receiving orthotopic and the other 42 receiving heterotopic conduit implantation. Conduit dysfunction-free, reintervention-free, and overall survival were not statistically different between both groups. There was 1 early and no late death up to the end date of our study.Conduits placed on a heterotopic position did not result in worse longevity, reintervention-free survival, as well as overall survival when compared to conduits placed on an orthotopic position. This suggested that the less technically demanding heterotopic conduit placement could be recommended as an operation of choice for right ventricular outflow tract reconstruction. Since the introduction of operations involving creation of right ventricle-to-pulmonary artery (RV-to-PA) connection in the 1960s , surgicaFurthermore, not only conduit position but also conduit types and sizes could impact their durability and patient’s reintervention-free and overall survival –7. HowevAs a result, we aimed to compare conduit longevity, reintervention-free survival, and overall survival between patients with congenital heart diseases indicated for operations involving RV-to-PA pathway reconstruction whose conduits were placed heterotopically to those with orthotopically placed ones as our primary endpoints. We also intended to identify potential risk factors for reduced conduit longevity as well as worse reintervention-free and overall survival in our patient population.The study protocol and ethical issues were reviewed and approved by Human Research Ethics Committee, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. We retrospectively collected data from electronic medical records of Ramathibodi hospital from 1st January 2005 to 31st December 2022. The total number of operations on congenital heart diseases was 406. We included all patients with congenital heart diseases whose operations involved reconstruction of RV-to-PA continuity, whether primarily or as a correction of previous operations. Patients whose operations were not relevant and whose medical record data were significantly missing  were excluded from our study. Ultimately, 339 patients were excluded, bringing to a total of 67 patients enrolled.Demographic data, operative  and postoperative details  were collected. Time-to-conduit dysfunction and reintervention, as well as overall survival time after operation were also collected.In our institution, we calculated body surface area (BSA) using Mosteller formula. Conduit cross-sectional area (CSA) was calculated from conduit diameter measured at the annular level. We then indexed the CSA with BSA, resulting in the term “CSA index” or “CSAi”.For heterotopic conduit implantation, the proximal end of the conduit would be trimmed, leaving about 3 mm of tissue remaining from the valve annulus. Posterior one-third of the circumference of the proximal anastomosis, or the “heel”, would be sutured directly to the right ventriculotomy incision at epicardial level Fig. . The remOrthotopic conduit implantation was mostly performed in patients with tetralogy of Fallot (TOF) who had undergone total correction with transannular patch presenting with recurrent pulmonary valve regurgitation (PVR), so-called secondary pulmonary valve replacement in our study. The transannular patch would be opened longitudinally with the regurgitant pulmonary valve subsequently excised. A new conduit was then orthotopically implanted as posteriorly as possible with its remaining exposed anterior rim covered with a patch to close the right ventriculotomy incision Fig. . In caseFor patients with concomitant pulmonary artery stenosis, we routinely performed pulmonary arterioplasty using either glutaraldehyde-fixed autologous or bovine pericardium as an enlargement patch. Techniques for other concomitant procedures would not be described in details in this study.Conduit type and size were mainly selected by the operating surgeon based on the individual’s preferences and conduit availability. Homografts which were deemed too oversized (more than + 2SD of the BSA) but with no smaller ones available would be bicuspidized in order to reduce their diameter to about two-thirds the original. We analyzed the final diameter after bicuspidization as the actual conduit diameter in our study Fig. .Fig. 4AnPostoperative echocardiographic evaluation was performed at 6 months to 1 year postoperatively. Subsequent evaluation would be performed half-yearly or yearly thereafter. We defined conduit dysfunction as having either moderate-to-severe degree of conduit stenosis (peak systolic pressure gradient across conduit > 40 mmHg) or moderate-to-severe degree of conduit regurgitation from echocardiographic parameters . ConduitPatient characteristics with continuous variables were compared using Student’s t-test while categorical variables were compared with chi-square or Fisher’s exact tests. P-value of less than 0.05 was considered statistically significant. Potential risk factors were analyzed by univariate and multivariate methods using Cox regression model. Independent risk factors were expressed as hazard ratios (HR) with 95% CIs. Survival analyses were performed using Kaplan–Meier method and evaluated with log-rank test. The statistical software used was Stata version 14.1.There were 67 patients included in our study, with 25 in orthotopic and 42 in heterotopic position group. Patients who underwent orthotopic conduit implantation were significantly older  and had generally bigger body sizes compared to those who underwent heterotopic conduit implantation . Also, there were significantly more patients diagnosed with TOF  in orthotopic position group . Systemic-to-pulmonary shunt procedures were performed significantly more in heterotopic position group  as the major diagnosis was pulmonary atresia and ventricular septal defect (PA/VSD) (52.38%). Co-morbidities were generally similar between both groups. All patients diagnosed with persistent truncus arteriosus (TA) underwent heterotopic conduit implantation as compulsorily required.2, P < 0.001, respectively) than in heterotopic position group. In terms of conduit type, the use of pulmonary homografts was similar between the two groups. There was no significant difference between the two groups in terms of conduit bicuspidization  or the concomitant procedures performed. The patient who had undergone concomitant aortic valve replacement had rheumatic severe aortic regurgitation along with double outlet right ventricle and severe pulmonary stenosis with no aortic root involvement, therefore, the operation was Rastelli operation with concomitant bioprosthetic aortic valve replacement.Heterotopic conduit implantation was associated with longer operative time compared to orthotopic conduit implantation . Similarly, heterotopic conduit implantation was also associated with longer cardiopulmonary bypass time  and aortic cross-clamp time  as all orthotopic conduit implantation procedures were performed on a beating heart basis. The median conduit size and cross-sectional area were significantly larger in orthotopic position group . However, there were no significant differences in left ventricular end-systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), fractional shortening (FS), and also tricuspid annular plane systolic excursion (TAPSE) between both groups. Postoperative peak systolic pressure gradient (PSPG) across conduit was also similar between both groups. There was a total of 26 conduit dysfunctions (12 in orthotopic and 14 in heterotopic group). Of the 12 patients with conduit dysfunction in the orthotopic group, 11 had moderate-to-severe conduit regurgitation while only 1 had moderate-to-severe conduit stenosis. On the other hand, of the 14 patients with conduit dysfunction in the heterotopic group, 10 had moderate-to-severe conduit regurgitation while the other 4 had moderate-to-severe conduit stenosis.There was no significant difference in hospital stay between the orthotopic and the heterotopic position group . However, the heterotopic position group had a significantly longer intensive care unit (ICU) stay compared to the orthotopic position group . There was also no significant difference in exercise capacity assessed at 6 months postoperatively between the two groups with most patients from both groups having improved postoperative exercise capacity (76% in orthotopic and 85.71% in heterotopic position group). Regarding echocardiographic parameters, the heterotopic position group had a significantly larger left ventricular end-diastolic volume index (LVEDVI) compared to the orthotopic position group . However, the conduit cross-sectional area index did not differ significantly between the two groups .The results showed that patients with conduit dysfunction had significantly larger conduit size and cross-sectional area than those without conduit dysfunction , reintervention , and worse overall survival . Diagnosis of double outlet right ventricle and pulmonary stenosis (DORV/PS) was associated with higher rate of conduit dysfunction  and reintervention , but not worse overall survival according to univariate analysis. Different types of previous surgeries were not significantly associated with better or worse outcomes.According to the Kaplan–Meier survival curves shown below, conduit dysfunction-free, reintervention-free, and overall survival were estimated to be statistically the same between patients who underwent heterotopic and orthotopic conduit implantation . The median time for conduit dysfunction-free survival was 123 months in orthotopic and 85 months in heterotopic group. For reintervention-free survival, it was 126 months in orthotopic and 96 months in heterotopic group. And lastly for overall survival, it was 144 months in orthotopic and 96 months in heterotopic group. Considering all patients in our cohort from both groups, the median time for conduit dysfunction-free survival, reintervention-free survival, and overall survival was 126, 191, and 78 months, respectively. The odd results were due to the increased heterogeneity of time when both groups were combined. There was 1 early  death due to postoperative pulmonary hypertensive crisis with progressive right ventricular failure and no late death.The history of surgical creation of right ventricle to pulmonary artery continuity could be traced back to the 1960s when Ross et al.  pioneereTechniques for surgical placement of a conduit on an orthotopic position are more demanding, as enlargement of the RVOT to accommodate the new, larger conduit would be necessary. Sometimes, the size of the newly-enlarged RVOT would still not be compatible to the conduits available, forcing surgeons to implant smaller-than-ideal conduits. Therefore, the technically simpler and more straightforward heterotopic conduit placement seems to be an interesting and more feasible option. However, there has only been a handful of studies directly conducted on this topic regarding the heterotopic conduit position on its longevity and possible negative effects on the patient’s need for reintervention and overall survival. One study  comparedConduit type and size, as well as patient’s age at operation, have been thought to have significant effects on conduit longevity –10. Our However, some believed that oversized conduits were associated with higher rate of conduit kinking and narrowing from sternal compression. As a result, these conduits were more prone to turbulent flow, which might increase their wall shear stress and cause earlier deterioration –14. CoroA few studies , 17 evalPulmonary hypertension could also affect conduit function. As in our study, the majority of patients receiving RV-to-PA conduit reconstruction were diagnosed with either TOF, PA/VSD, or DORV/PS. These diseases on their own generally resulted in restricted pulmonary blood flow, which would not result in pulmonary vascular obstructive disease (PVOD). Therefore, they might not have negative effects on conduit function and longevity. However, with the rarer diagnosis of TA, which resulted in pulmonary overflow, the results might prove otherwise. Our results did not demonstrate TA to be a potential risk factor for conduit dysfunction, reintervention-free survival, and overall survival. We believed that the reason behind this was that patients with TA generally underwent surgical conduit placement much earlier in life, in which PVOD had not yet developed , 19. AlsA few studies –23 compaDecellularized homografts, on the basis that they lacked living cells, would result in less immune reactions and possibly longer conduit durability , 25. OthCryopreservation theoretically would result in elimination of living cells in conduits, leaving only the “scaffolding” remaining . From thSurgical technique-wise for heterotopic conduit implantation, we routinely sutured proximal conduit anastomosis to the right ventricular (RV) epicardium , not burWe calculated conduit CSA  indexed Bias could not be fully eliminated as this was a retrospective trial. Also, we did not have a regularly-scheduled echocardiographic follow-up appointment protocol in our hospital. This was mainly due to the availability of the echocardiography laboratory and also the attending pediatric cardiologists. Another limitation regarding echocardiography was the recorded parameters in which some were either not mentioned or lost, resulting in incomplete postoperative echocardiographic parameters for our final analysis.Secondly, as mentioned earlier, choice of operation and conduit type were mainly made based on the operating surgeon’s preferences, resulting in possible biases. Also, there were no clearly defined indications for reintervention in patients with conduit dysfunction at our institution. This could probably result in either over- or under-reintervention for our patients.Lastly, as with many other studies, we had limited number of patients included in our study. With diagnoses of TOF (who needed RV-to-PA reconstruction), DORV/PS, and TA being relatively rare compared to other kinds of congenital heart diseases or adult cardiac diseases, larger patient population would be too difficult to come by. Also, randomized-controlled trials on this topic would be too time-costly or even nearly impossible to realistically conduct.As for creation of RV-to-PA continuity, conduits placed on a heterotopic position did not result in worse longevity, reintervention-free survival, as well as overall survival when compared to conduits placed on an orthotopic position. The less technically complicated heterotopic conduit placement could be strongly recommended as an operation of choice for RVOT reconstruction according to our results. Also, choosing a moderately oversized conduit would be advisable to mitigate the degree of patient outgrowing the conduit, which we believed to be an important risk factor for conduit dysfunction. Lastly, we encouraged the use of CSAi as a useful new term to accurately and reliably compare between different conduit sizes.


Objective: We aimed to study the long-term association of LV mass index (LVMI) and myocardial fibrosis with ventricular arrhythmia (VA) in a population of patients with confirmed hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance imaging (CMR). Methods: We retrospectively analyzed the data in consecutive HCM patients confirmed on CMR referred to an HCM clinic between January 2008 and October 2018. Patients were followed up yearly following diagnosis. Baseline demographics, risk factors and clinical outcomes from cardiac monitoring and an implanted cardioverter defibrillator (ICD) were analyzed for association of LVMI and LV late gadolinium enhancement (LVLGE) with VA. Patients were then allocated to one of two groups according to the presence of VA (Group A) or absence of VA (Group B) during the follow-up period. The transthoracic echocardiogram (TTE) and CMR parameters were compared between the two groups. Results: A total of 247 patients with confirmed HCM  were studied over the follow-up period of 7 ± 3.3 years (95% CI = 6.6–7.4 years). LVMI derived from CMR was higher in Group A  when compared to Group B. LVLGE was higher in Group A  when compared to Group B. Multivariable Cox regression analysis showed LVMI (hazard ratio (HR) = 1.02, 95% CI = 1.001–1.03, p = 0.03) and LVLGE  to be independent predictors for VA. Receiver operative curves showed higher LVMI and LVLGE with a cut-off of 85 g/m2 and 6%, respectively, to be associated with VA. Conclusions: LVMI and LVLGE are strongly associated with VA over long-term follow-up. LVMI requires more thorough studies to consider it as a risk stratification tool in patients with HCM. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition with an incidence of 1 in 500 births, characterized by cardiac hypertrophy, usually asymmetrical with the greatest involvement of the basal interventricular septum, with wall thickness ≥ 15 mm in adults or ≥13 mm without higher loading conditions ,3,4,5,6.HCM may present with symptoms of exertional fatigue, dyspnea, syncope, sudden cardiac arrest (SCA), or sudden cardiac death (SCD), or incidentally identified during routine screening with abnormal electrocardiogram ,8,9,10.HCM is classified according to morphological appearance or genetic phenotype . InitialOver the last few decades, the development of imaging modalities has significantly changed our understanding of HCM phenotypes, disease progression and management ,3,5,9. THCM is recognized as the major cause of mortality among young individuals. The annual incidence of sudden cardiac death (SCD) is 0.5–1%. The percentage of SCD is higher among younger patients with HCM and decreases with aging. Current guidelines endorse an implantable cardioverter defibrillator (ICD) for secondary prevention and for primary prevention of SCD in high-risk individuals with HCM .SCD has been the most deleterious complication of HCM for more than half a century, mainly in those of a young age. The implementation of ICDs over the last two decades for both secondary and primary prevention of high-risk HCM patients significantly ameliorated the outcome of HCM patients. Several risk schemes have been developed to identify high-risk patients in need for primary ICD employment. However, controversy remains for the optimal risk stratification scheme to identify high-risk patients .WT), LV mass index (LVMI) and scar quantifying using left ventricle late gadolinium enhancement (LVLGE), which has shown to be a positive predictor of SCD [MI is currently not described as a risk factor for SCD in patients with HCM [The American Heart Association (AHA), the American College of Cardiology (ACC) and the European Society of Cardiology (ESC) developed risk stratification models to improve the prediction of SCD with the inclusion of more risk factors ,14. Multr of SCD ,19,20. Lwith HCM .HCM patients report a higher incidence of arrhythmias, including atrial fibrillation, ventricular premature beats (VPB), non-sustained ventricular tachycardia (NSVT), sustained ventricular tachycardia (SVT), ventricular fibrillation (VF), heart failure and SCD compared to the general population of a similar age ,22. MultMI and LVLGE in HCM patients.We aim to retrospectively study the impact of LVMI and LVLGE with VT.To evaluate the association of LVTo compare differences in the ESC risk score using TTE and CMR.The main objectives of this retrospective study are:Our study is a retrospective longitudinal observational study that included consecutive patients referred to outpatient HCM clinics of a single tertiary center with HCM diagnosed/confirmed diagnosis on CMR and followed between 2008 and 2018.Local ethics committee approval was obtained from the Research and Development office of Nottingham University Hospitals NHS Trust, ID20-148C. The study was designed in 2018 and, at the time of conceptualization and design, no patient or public involvement was required or obtained for this retrospective study.WT ≥ 15 mm in adults or ≥13 mm in patients with a genetic mutation, after exclusion of secondary causes [WT was measured on TTE in the parasternal long- and short-axis views at end diastole using a standard calibration scale [Baseline demographics and risk factors were retrieved from completed clinical records. HCM diagnostic criteria was LVy causes ,11. Initon scale . ICDs weon scale ,3,14. YeFor primary outcome, patients were divided into two groups:NSVT: ≥3 consecutive ventricular beats ≥120 beats per minute captured on ECG, Holter monitoring or cardiac implantable electronic device (CIED) during follow-up.Therapy: Appropriate anti-tachycardia pacing (ATP) or cardioversion/defibrillation provided by ICD or external cardioversion for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).Group A: patients with an incidence of VA:Group B: patients who had no VA detected during the follow-up and no ICD therapies.CMR examinations were performed using 1.5T scanners  and a commercial cardiac coil. Electrocardiographic-gated, steady-state, free breath-hold sequential cines of 10 mm short-axis slices were acquired starting parallel to the atrioventricular ring and covering the entire ventricle. Late gadolinium enhancement images were acquired 15 min after the intravenous administration of 0.2 mmol/kg of gadolinium-DTPA . A 2D segmented inversion-recovery sequence with breath-hold was acquired in the same views as the cine images.WT was defined as the greatest dimension at any site within the LV wall (LGE), all short-axis slices from base to apex were inspected visually to compare with areas of normal myocardium. Myocardial fibrosis was quantified at a grey-scale threshold of six standard deviations (SDs) above the mean signal intensity for normal myocardium , as shown in  LV wall . To asseocardium . The quaial mass . The LVLt-test and presented as mean and SD. Non-parametric continuous values were analyzed using the Mann–Whitney test and presented as median and interquartile ranges. All categorical values were statistically analyzed using chi-square test or Pearson–Spearman test. Univariable Cox regression hazard proportional analysis was performed to evaluate hazard ratios (HR) and 95% confidence intervals (CI). Univariable results with p value < 0.1 were used in multivariable Cox regression analysis to establish if there was independent predictor of VA as defined in the methodology. Variance inflation factor was used to detect collinearity.All parametric continuous values were statistically analyzed using Student’s MI and LVLGE as a test to predict VA. Negative and positive predictive values (NPV and PPV) were calculated for LVMI and LVLGE. These cut-off values were applied to measure incidence of VT using Kaplan–Meier curves measured using log rank test and HR. Correlation between LVMI and LVLGE was measured using linear regression and Bland–Altman plots. Statistical p values < 0.05 were considered significant. SPSS version 25 or higher  were used for statistical analysis.Receiver operative characteristic (ROC) curve analysis was used to define optimal cut-off values for LVp = 0.75), and death from all causes during follow-up .Our study included data of 252 patients  with confirmed HCM, and were followed up for an average of 6.6 ± 3.3 years. Baseline demographics and imaging measurements of all the subjects are listed in p < 0.01. SCD was aborted in 7 out of the 24 ICD patients in Group A by therapies delivered by ICD (n = 5) and external defibrillation (n = 2).Patients with increased ESC risk had an ICD inserted (35 patients): 19 patients before 2014 and 16 patients after the 2014 guidelines. Twenty-four patients (38.1%) of Group A had ICD insertion compared to eleven patients (6.0%) of Group B, WT was higher compared to TTE in all patients . CMR LVWT was significantly higher in Group A compared to Group B . CMR-measured LVMI was significantly higher in Group A compared to Group B , Additionally, LVLGE was also higher in Group A , as shown in CMR-measured LVMI had a weak correlation with LVWT derived from CMR (R2 = 0.245) and TTE (R2 = 0.098) (WT was weakly correlated between CMR and TTE (R2 = 0.279) (MI was poorly correlated with LVLGE (R2 = 0.002) (LV= 0.098) . LVWT wa= 0.279) . LVMI wa= 0.002) .Cox regression univariable and multivariable analyses were performed to identify predictors for VA prior to the event in the HCM population, as shown in WT , CMR LVMI  and LVLGE  were associated with VT. Multivariable Cox regression analysis showed CMR LVMI  and CMR LVLGE  to be the only independent predictors of VT.Univariable Cox regression analysis shows TTE LVMI  and LVLGE  to be good markers for VT  and for LVLGE >6%  were used in Kaplan–Meier analysis to evaluate freedom from VT.ROC curve analysis showed LVs for VT . A cut-oMI < 85.0 g/m2 compared to LVMI > 85 g/m2   .LGE < 6% compared to LVLGE > 6%   .MI is associated with VA and can be considered for risk stratification of SCD in HCM.Higher LVMI > 85 g/m2 and LVLGE > 6% are associated with VA.LVWT using TTE or CMR was only weakly correlated with LVMI on CMR.LVMI and LVLGE were independent predictors of VA during follow-up.LVOur study is one of the longest retrospective studies to observe HCM patients, and the main findings are as follows:CMR has superior spatial resolution and provides a multidimensional reconstruction of the heart. However, current guidelines are still considering CMR only for elucidation of diagnosis when there is a diagnostic dilemma, and do not include CMR for risk stratification for patients with HCM .HCM risk score using TTE and CMRWT > 30 mm as a major risk factor for SCD and LVWT measured by TTE was incorporated into the European HCM Risk-SCD calculator [MI and LVWT assessments are limited by asymmetric distribution of hypertrophy, echo window limitations resulting in underestimating or overestimating maximum LVWT, the inclusion of papillary muscles and right ventricular insertion into LV [WT assessed with TTE vs. MRI. Śpiewak et al. developed a simulation model comparing LVWT measured by TTE vs. CMR for risk stratification according to the European HCM Risk-SCD calculator. The discrepancy for which CMR measured LVWT translated to significant differences in the five-year risk of SCD [American guidelines identified LVlculator . TTE is  into LV ,29,30,31k of SCD .WT and LVMI assessment compared to TTE [CMR allows earlier and accurate diagnosis of HCM with early detection of myocardial fibrosis ,14,30,31d to TTE ,32,33, pd to TTE ,14,30.LGE identified and reclassified certain population underestimated with conventional risk scores [Another study showed the valuable role of using CMR in risk stratification of HCM patients. A study by Freitas et al., 2019, conducted a multicenter retrospective analysis of HCM. The study included 493 patients with median follow-up of 3.4 years. Their study showed that LVk scores .WT, LVMI and myocardial fibrosis on cardiac events and prevention of SCDImpact of LVWT as an independent predictor for VA [WT to predict outcomes in patients with HCM is limited, with literature controversy. LVM offers more reliable representation of total LV hypertrophy compared to single wall thickness measurement, as shown in our study. Several studies highlighted the value of LVMI as an independent predictor for SCD. CMR is more accurate in the assessment of LVMI [Short-term and long-term studies have identified LVr for VA ,35,36. H of LVMI ,32,33.MI is an independent predictor for a major event and myocardial fibrosis (LVLGE) is a significant predictor for arrhythmia. Their patients were followed for an intermediate term (3.8 ± 2.4 years). The arrhythmia endpoint included malignant ventricular arrhythmia and appropriate ICD therapy. The incidence of death from all causes during follow-up was 10.7% (20/187) of patients. It is noted that their study population was younger (46.6 + 18.4 years) compared to our study (56.2 ± 16.3 years). Patients with ventricular arrhythmias had greater LVMI of 126.2 ± 56.5 g/m2 and greater percentage of myocardial fibrosis of 13.1 ± 8.7% [A recent retrospective study of 187 HCM patients by Dohy et al., 2021, demonstrated that CMR-derived LV1 ± 8.7% ,37.LGE territories revealed a significant correlation between myocardial fibrosis and the abnormalities of catheter-mapped electrophysiological parameters in relation to the occurrence of malignant ventricular arrythmias. Ventricular arrythmia could be linked to conduction block created by myocardial fibrosis, and re-entry circuit created by residual non fibrotic myocardium [LGE. The risk of SCD is linearly related to LVLGE. Myocardial fibrosis > 15% was associated with a two-fold increased risk of SCD [Myocardial fibrosis is another independent predictor for ventricular arrythmias, as shown in our study. Electrophysiological study of CMR LVocardium ,39,40,41k of SCD .MI and LVLGE and incidence of ventricular arrhythmias. Further investigations are required to assess the utility of adding CMR-derived markers for risk stratification of patients with HCM and improve identification of patients with HCM requiring ICDs for SCD prevention [There is a great interest in CMR-derived markers for risk assessment of patients with HCM. Our long-term study displayed significant association between LVevention . MyocardLGE has limitations with sequences, heart rate and kidney disease. Hence, LVMI might be a more suitable, reproducible option without added software renderings and post-processing that is required for LVLGE for risk stratification. LVMI can be researched by conducting a randomized control study allocating moderate-risk patients with LVMI > 85 g/m2 to either receive an ICD or a long-term continuous monitoring device such as an implantable loop recorder (ILR) for continuous risk assessment looking for NSVT as opposed to using extended ambulatory monitoring with poor diagnostic yields.Trientine demonstrated increased urinary copper excretion, with improvement in cardiac strain function along with a reduction in LV mass in this population . LVLGE hThere were limitations in our study related to retrospective data acquisition. The capture of VA using Holter monitoring is likely to result in underestimation compared to ICD monitoring, and the use of implantable loop recorders would give a more accurate capture of VA. Another limitation was the use of a combined endpoint e.g., NSVT, ATP and ICD shock. The last major limitation is that non-sustained VT does not necessarily translate to SCD over five- to ten-year follow-up, although this has not been extensively studied.MI and myocardial fibrosis are strongly associated with ventricular arrhythmias over long-term follow-up of HCM patients. The utility of these CMR markers as risk stratification tools needs to be further investigated in a randomized control study.LV


Background: The development of atrial fibrillation adds a lot to the morbidity and mortality of individual patients. The spectrum of non-valvular atrial fibrillation among young adults is less known. The present observational study aims to analyze the clinical-aetiological spectrum of non-valvular atrial fibrillation among young adults between 18 and 40 years of age.Methods: A retrospective observational study was carried out to analyze the clinical-aetiological spectrum of non-valvular atrial fibrillation among young adults less than 40 years of age attending the cardiac outpatient department in a tertiary care hospital in Eastern India over a period of two years. Patients with any form of organic valvular heart disease and patients more than 40 years of age were excluded from the study. One hundred and seventeen patients under 40 years of age were analysed with respect to demographic, aetiological, and clinical profiles.Results: Most common aetiologies behind non-valvular atrial fibrillation in young adults (<40 years) were hypertension (40%) and the presence of left ventricular systolic dysfunction (31%). Thyrotoxicosis, obesity, obstructive sleep apnoea, the presence of congenital heart disease, coronary artery disease, myopericarditis, chronic kidney disease, dyselectronemia, diabetes mellitus, and the presence of chronic obstructive pulmonary disease contributed towards the development of non-valvular atrial fibrillation in the young population in less proportion of cases. Most of the cases were symptomatic with palpitation, shortness of breath, or diaphoresis. Less number of cases (17%) had left atrial thrombus which may be due to early clinical attention with the proper therapeutic anticoagulation regimen.Conclusions: Hypertension and the presence of left ventricular systolic dysfunction contribute to the majority towards the development of non-valvular atrial fibrillation among young adults. Accurate measurement and monitoring of blood pressure among young adults and careful assessment of left ventricular systolic dysfunction with subsequent appropriate management of hypertension and left ventricular systolic dysfunction in young can decrease the burden of non-valvular atrial fibrillation among the young population. Atrial fibrillation is considered an old-age phenomenon among practising physicians and general people. The burden of non-valvular atrial fibrillation in the real-world scenario is yet unknown as most patients with atrial fibrillation present late unless they suffer from an episode of fast ventricular rate or heart failure. The profile and spectrum of non-valvular atrial fibrillation among relatively young adults are yet unknown. Early recognition of atrial fibrillation in young adults can save them from the devastating morbidity and mortality of young adults with stroke  which maAim and objectiveThe aim of this study was to retrospectively study and analyze the aetiology and clinical profile of young adults with non-valvular atrial fibrillation in a tertiary care centre in Eastern India.Inclusion criteriaPatients between 18 and 40 years of age with non-valvular atrial fibrillation were included.Exclusion criteriaPatients with any form of organic valvular heart disease , end-stage organ disease , malignancy, sepsis, and not willing to participate in the study were excluded.The study was conducted in a tertiary care centre in Eastern India between May 2020 and 2022. Sample size calculation was done using the standard formula with the power of the study being 80% and an attrition rate of 15%. After obtaining the institutional ethical clearance from the institutional ethics committee (IEC) of All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India (Ref: TE/IM-NF/CTVS/22) for retrospective analysis, we analysed the data of 117 patients attending the outpatient department of Cardiology and Cardiothoracic and Vascular surgery between May 2020 and 2022. Informed telephonic oral patient consent was obtained from each of those patients prior to analysis. The hospital outpatient department (OPD) case sheet record of each patient was obtained and analysed for brief history including the nature and duration of disease onset, presence of shortness of breath (New York Heart Association Classification (NYHA) Class), palpitation and its nature, diaphoresis, or exercise intolerance. Demographic details and clinical profiles of each patient were obtained from the OPD case sheet record. Baseline ECG and echocardiography parameters of each patient were also obtained from the OPD case sheet record of each patient. ECG was analysed for the rhythm, and individual echocardiography report was analysed for definite aetiology and the presence of thrombus in the left atrial appendage or left ventricle. Data were entered in Microsoft Excel software 2021  in tabular form. All nominal and ordinal variables were represented in tabular form, and descriptive statistics was used to analyze the data in SPSS software (version 21) .Table Table Table Non-valvular atrial fibrillation in the young population comprises an important clinical entity. Fibrotic atrial remodelling, breaking down of atrial impulses into small wavelets, non-homogeneous conduction of atrial impulses across the atrium, and anomalous firing of pulmonary veins result in atrial fibrillation in the young population. Early recognition of atrial fibrillation in the young population can prevent them from myriad and devastating complications like embolic central nervous system stroke and peripheral stroke. We tried to delineate the aetiology behind young patients with atrial fibrillations, stratified them according to the clinical profile, and managed those patients with a proper anticoagulation regimen to prevent embolic stroke. We adopted the classification given in the article by Horng et al. of age groups to define young adults who are less than 40 years of age [Our study demonstrated that non-valvular atrial fibrillation was more common after the third decade among the young adult population as atrial compliance starts failing after the third decade of life. At a relatively younger age, atrial fibrillation is quite uncommon as atrial compliance is quite good and the atrium does not suffer acute stretch even if it faces an acute rise in the atrial pressure and conduction is also homogenous. Males constituted the majority of the study population as it is known that atrial fibrillation is a male predominant disease. Atrial fibrillation is more common in males due to a shorter atrial refractory period and larger left atrial size favouring re-entry and atrial fibrillation. Atrial fibrillation is divided into two types: adrenergic atrial fibrillation and vagotonic atrial fibrillation. As males often carry out outdoor activities in India, they suffer from exercise-induced adrenergic atrial fibrillation more as compared to females.The most common aetiology behind non-valvular atrial fibrillation in young adults was hypertension. The association between hypertension and atrial fibrillation is well established. Hypertensive patients carry a 14% additional risk of developing atrial fibrillation , and theThe second most common cause of non-valvular atrial fibrillation in young adults was dilated cardiomyopathy in whom 55.56% were non-ischemic dilated cardiomyopathy (NICM). Rest were ischemic cardiomyopathy in the young who suffered a myocardial infarction long back, and the culprit artery was not revascularised leading to cardiomyopathy. About 30%-40% of patients with left ventricular systolic dysfunction develop atrial fibrillation in due course of time -9. The mThe commonest social factor behind the development of non-valvular atrial fibrillation in young (15%) was alcohol intake or binge drinking. The association between alcohol intake and atrial fibrillation is well-established . AlcoholThyrotoxicosis induced atrial fibrillation by exaggerating sympathetic drive and inducing adrenergic atrial fibrillation. About 8.3% of thyrocardiac patients develop atrial fibrillation as the disease progresses ,12. BothFive per cent of our patients were obese where obesity was the cause of atrial fibrillation emphasising the deleterious effect of lipotoxicity on the heart. The presence of a large amount of pericardial fat contributes to the development of atrial fibrillation by producing inflammation . Obese pChronic kidney disease (CKD) produces atrial fibrillation by producing electrolyte imbalance in the form of hypokalaemia, hyponatraemia, hypomagnesemia, and hypocalcaemia. Altered intracellular electrolyte hemostasis induced abnormal atrial firing and atrial fibrillation. The risk of developing atrial fibrillation in CKD patients increases directly with the risk of decreasing glomerular filtration rate (GFR) . The assNine per cent of young adults with atrial fibrillation were secondary to congenital heart disease out of which atrial septal defect was the commonest. Atrial fibrillation occurs in approximately 20% of patients with atrial septal defect . It alsoMost patients in our study had paroxysmal atrial fibrillation as in a young heart the sinus node dominates the rhythm most often and fibre inhomogeneity is not there in the young heart to produce inhomogeneous conduction and atrial fibrillation. There exists a dictum in the treatment of atrial fibrillation: “Every atrial fibrillation should be provided one chance to return to sinus rhythm by either mechanical or chemical cardioversion”. We opted for cardioversion in all patients with permanent atrial fibrillation. Most of the young patients with atrial fibrillation were symptomatic (90%) with raised NT-proBNP (40% of cases). Atrial fibrillation in young most often presents with a fast ventricular rate. During the episode of atrial fibrillation, both atria behave like a lake full of water, and passive congestion in the pulmonary veins gives rise to dyspnoea.Acute coronary artery disease was present in 4% of cases where 3% were having inferior wall myocardial infarction having lesions in the right coronary and left circumflex artery and only 1% was having anterior wall myocardial infarction. The atrial fibrillation in inferior wall myocardial infarction was transient in nature and it responded to beta blockers. The atrial fibrillation in anterior wall myocardial infarction was non-responsive to beta blocker and needed chemical cardioversion with amiodarone. Atrial fibrillation occurs in 6%-10% of cases with acute myocardial infarction  due to iTwelve per cent of cases in our study had diabetes mellitus. Diabetes mellitus is an independent risk factor behind atrial fibrillation by producing fibrotic atrial remodelling through advanced glycosylation end products ,23. EpisFive patients with hypertrophic cardiomyopathy developed atrial fibrillation. Atrial fibrillation is the most common arrhythmia in hypertrophic cardiomyopathy. Atrial fibrillation occurs in 10%-28% of patients with hypertrophic cardiomyopathy  secondarAtrial fibrillation is usually considered an elderly phenomenon among physicians and the general population. Non-recognising atrial fibrillation in the young population leads to cryptogenic stroke in the young with associated morbidity and mortality. Our study presents a new insight into the clinical-aetiological profile and spectrum of non-valvular atrial fibrillation in the young adult population. Early scrutiny and management of those cohorts of patients can prevent the population from the morbid consequences of atrial fibrillation.The present study provides insight into the profile and spectrum of non-valvular atrial fibrillation in relatively young populations contrary to the belief that atrial fibrillation is an elderly phenomenon. Hypertension and cardiomyopathy with left ventricular systolic dysfunction contribute towards the development of non-valvular atrial fibrillation in the majority of young adults followed by unrecognised congenital heart diseases, thyrotoxicosis, obesity, and obstructive sleep apnoea. Myopericarditis, chronic kidney disease, dyselectronemia, young-onset diabetes mellitus, and chronic obstructive pulmonary disease also contribute to the development of non-valvular atrial fibrillation among young adults. Atrial fibrillation among young adults makes them symptomatic early, and early therapeutic anticoagulation mitigates the risk of future embolisation by having a thrombus in the left atrial appendage or left ventricle. Careful measurement of blood pressure and careful assessment of left ventricular systolic dysfunction with proper therapeutic measures in young adults can save them from the morbidity and mortality of early-onset non-valvular atrial fibrillation.


P = 0.017), accompanied by a significantly increased proportion of patients with NYHA class I and II, as well as the 6MWT. Compared with standard biventricular pacing, LVEDD was significantly shortened (P = 0.045), accompanied by significantly improved LAD, AVVTI, EA distance/RR, IVMD, and TS-SD after the operation. RAS–RVS was 156 ± 33 ms, the optimized AVI was 102 ± 10 ms, and LUBBPε was calculated to be 0.66 ± 0.06. Depending on the LUBBPε, a three-chamber pacemaker with a single left bundle branch pacing system was developed based on RAS–RVS-optimized AVI automatically. A three-chamber pacemaker with single left bundle branch pacing can achieve CRT based on RAS–RVS, reaching the optimal AVI of 66% of RAS–RVS.To examine the feasibility of single left bundle branch pacing for cardiac resynchronization therapy (CRT) by carrying out a frequency adaptive atrioventricular delay (RAAVD) algorithm and automatic optimization of the single left bundle branch pacing atrioventricular interval (AVI) based on the right atrioventricular interval (RAS–RVS). Thirty-six patients with CRT class Ia indications according to the European Society of Cardiology 2016 guidelines and implanted with RAAVD functional three-chamber pacemakers were prospectively enrolled in this study. Patients were divided into a single left bundle branch pacing group (n = 21) and a standard biventricular pacing group (n = 15). The optimization of the two groups was performed under standard cardiac colour Doppler ultrasound, followed by the comparison of the QRS width, cardiac function improvement, and echocardiography indicators. The ratio of AVI to the right atrial-right ventricular interval (RAS–RVS) after single LV pacing optimization was defined as the single left bundle branch pacing coefficient (LUBBPε). In comparison to the BVP, the QRS was significantly narrowed ( However, approximately 30–40% of patients still fail to respond well or even do not respond to conventional biventricular pacing during treatment. In comparison to His bundle pacing (HBP), left bundle branch pacing (LBBP), as an alternative pacing therapy to His-Purkinje system pacing, can eliminate multiple downsides of HBP and provides a low and stable threshold with a unique correction of the distal conduction system benefitting from the anatomical and electrical characteristics6. In fact, there is sufficient evidence that fusion pacing, in which cardiac conduction is transmitted down the atrioventricular node (AVN) to the right ventricle to fuse with LV pacing, can achieve the best haemodynamic stability and finally achieve cardiac synchronization.Cardiac resynchronization therapy (CRT) serves as a critical treatment strategy for patients with symptomatic heart failure, left ventricular (LV) dysfunction and cardiac electrical desynchrony14. Left univentricular pacing (LUVP) even serves better than, or at least not worse than, BVP18. Physiologically, the atrial-ventricular delay (AVD) will vary dynamically with the change in heart rate to achieve the filling effect of the atrium on the ventricle and elevate ventricular ejection, posing a serious challenge to fusion pacing. LUVP can be completed through AVD, which can provide optimal fusion between sinus rhythm down the atrioventricular node (AVN) to the right ventricle and LV pacing8.In fact, there is sufficient evidence that fusion pacing, in which sinus rhythm is transmitted down the atrioventricular node (AVN) to the right ventricle to fuse with LV pacing, can achieve the best haemodynamic stability and finally achieve cardiac synchronization20. Depending on the above algorithm, LUVP can realize CRT. However, the adaptive CRT algorithm works based on traditional CRT, in which LV electrodes are generally implanted in the lateral or posterior LV veins, accompanied by an AVI equal to 70% of the intrinsic AVD. When the implantation of the LBBP LV electrode is below the LBBB point and located in the conduction system region of the heart itself, the transformation in the ratio of the optimal AVI to the inherent AVD will also occur, with the specific value unproposed. The aim of this study was to investigate whether single left ventricular pacing in the left bundle branch area is noninferior to BVP in terms of QRS duration, cardiac function, and echocardiographic parameters. A new concept is proposed. The ratio of AVI optimized by single left bundle branch pacing to the right atrioventricular interval (RAS–RVS) was defined as the single left bundle branch pacing coefficient (LUBBPε), which was the ratio of the optimal sensed atrioventricular interval (SAV) to the intrinsic atrioventricular interval . The aim of this study was to develop an automatically optimized single left bundle branch pacing system for a three-chamber pacemaker. This system can automatically optimize the physiological state of the atrioventricular interval (RA–RV) according to the single left bundle branch pacing coefficient (LUBBPε).Adaptive CRT algorithm: This algorithm can achieve the dynamic optimization of CRT pacing (BiV vs. LV) and AV/VV intervals. If the intrinsic AVD is normal and without a heart rate exceeding 100 beats per minute, the algorithm provides optimized single LV pacing with an AVI equal to 70% of the intrinsic AVD, in which LV pacing can be fused with RV excitatory revealing more stable haemodynamicsThirty-six patients with chronic heart failure and left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm, complete left bundle branch block (LBBB), QRS duration ≥ 150 ms, NYHA class II–IV under optimal medical therapy were enrolled in this study. Thirty-six patients signed informed consent to be implanted with a three-chamber pacemaker with rate-adaptive atrioventricular delay (RAAVD) function. The patients were matched by age, sex, QRS duration, NYHA functional class and 6-min walk test. According to the individual differences and specific intraoperative conditions, the patients were divided into a single left bundle branch pacing group (21 patients) and a standard biventricular pacing group (15 patients). Each patient was optimized before the operation and 1, 3, 6, and 12 months after the operation, and the last follow-up time prevailed. Patients were excluded if they had any of the following conditions: (1) atrioventricular block; (2) right bundle branch block; (3) patients with a life expectancy less than 1 year; (4) patients with potentially reversible cardiomyopathy; (5) patients undergoing heart transplantation or waiting for heart transplantation; (6) patients with cardiac valves; (7) patients with hypertrophic obstructive cardiomyopathy; and (8) patients unable to participate in the follow-up. The study was approved by the institutional ethical review board of the hospital. All methods in this study were performed in accordance with relevant guidelines and regulations.All three chamber pacemakers were from Medtronic. The models are as follows: Synacra C2TR01 CRT, Maximo II CRT-D, Insync Sentry 7298 CRT-D, Egida D394TRG CRTD, Brave DTBC2QQ, and D7BC2D1 CRTD. DTBA2D4/D1 CRTD.In this study, the QRS complex was measured from the end of the pacing pulse to the end of the QRS complex, namely, S-QRS.The ultrasound and synchronization indexes in both groups were measured before the operation and 1 month, 3 months, 6 months and 12 months after the operation. Normal cardiac ultrasound indicators referred to left ventricular ejection fraction (LVEF), left atrial dimension (LAD), left ventricular end diastolic dimension (LVEDD), and aortic valve velocity time integral (AVVTI). The synchronization index included the following: (1) Atrioventricular synchronicity: EA distance/RR; (2) Interventricular synchrony: Interventricular mechanical delay time (IVMD); (3) Left intraventricular contractive synchrony: standard deviation of time intervals of the 12 LV segments (TSI-12S-D).Preoperative 24-h Holter examination was performed. PR interval was measured at HR 60, 65, 70... and the highest heart during sinus rhythm. Taking heart rate as the independent variable (x) and the change of PR interval as the dependent variable (y), the function y = ax + b was established to calculate the change of PR interval from the change of heart rate as the basis for setting the frequency adaptive AV to ensure the real-time and accurate tracking of the physiological PR interval of the dynamic changes of the right. In this way, the LV pacing can form an optimal fusion wave with the excitation transmitted down from the right His-Purkinje system to realize the CRT. Note: a is a constant term and b is a standardized partial regression coefficient. The PR interval corresponding to the lower rate interval (LRI) and upper rate interval (URI) can be derived according to this formula, which can serve as the basis for setting the parameters of RAAVD Fig. .Figure 1NYHA and 6MWT were used to evaluate preoperative and postoperative cardiac function.After the operation, the BVP was set. AVI was titrated bidirectionally (prolonged or shortened) with a step size of 10 ms, of which the most optimized was obtained with the smallest MRA and IVMD, the largest AVVTI and the narrowest QRS wave.The three-chamber pacemaker was programmed for single LV pacing, in which only sensing and defibrillation functions were retained, and the VS was set to the right ventricle by default. The default atrial sense compensation (ASC) was 30 ms. The atrioventricular interval (AVI) was prolonged until the intracardiac maps are showing AS-VS indicated, and the AS-VS interval (RA–RV) interval was measured. Based on the ASC subtracted from the interval of AS-VS (RA–RV), bidirectional titration was performed in 10 ms steps, and the titrated AVI was shown under echocardiography. When the LVEF and AVVTI were the largest and the MRA was the smallest, and QRS was narrowest, it was the optimal AVI, that is, the best AVI of the left atrioventricle at a specific heart rate . The single left bundle branch pacing coefficient (LUBBPε) was calculated. The average of the two results was used as the single left bundle branch pacing coefficient in this patient and was recorded.The start rate was set as the lower limit rate (LRI) of the pacemaker, and the stop rate was set as the upper limit rate URI of the pacemaker. The RAAVD parameters were set according to the PR interval at different heart rates of Holter collected before operation or the regression equation of the relationship between heart rate change and PR interval established by Holter. SAV interval for start rate/at stop rate = optimal AVI+ . In terms of three-chamber pacemakers, the optimized RAS–RVS can be adopted instead of the optimized PR interval. PAV = SAV + ASC. When RAAVD is turned on, the atrioventricular interval of the pacemaker can be dynamically set according to the RAAVD parameters to synchronize left and right ventricular electrical activation, complete fusion pacing, and realize CRT.P < 0.05 after correction was considered a significant difference.Data were analysed using SPSS 22.0 for Windows . When the numerical data conformed to normality, the mean (standard deviation) was used to describe the homogeneity of variances and was compared with the T test. Otherwise, the data are described by the median with the maximum and minimum, and the nonparametric test was used. The chi-squared test was used for enumeration data. For all statistical analyses, The study protocol was reviewed and approved by the Medical Ethics Committee of the First Affiliated Hospital of Kunming Medical University in accordance with the 1964 Declaration of Helsinki and its later amendments.No cardiovascular death occurred during the follow-up period Table .Table 1BIn comparison to the BVP group, the QRS complex was significantly narrowed, accompanied by a significantly increased proportion of patients with NYHA class I and II, as well as the 6MWT Tables , 3.TableCompared with BVP, LVEDD was significantly shortened, accompanied by significantly improved LAD, AVVTI, EA distance/RR, IVMD, and TS-SD after the operation in the single left bundle branch pacing group Tables , 5.TableAutomatic optimization algorithm of single left bundle branch pacing based on RA–RV interval in three-chamber pacemaker. LUBBPε = optimized AVI (SAV)/ RAS–RVS  = 0.66 ± 0.06.The results demonstrated that CRT can be achieved by optimizing AVI depending on the RAS–RVS interval in a three-chamber pacemaker with single left bundle branch pacing, with the optimal AVI being 66% of the RAS–RVS interval. Based on the current V–V interval program of three-chamber pacemakers, one step per 10 ms, a three-chamber single-left bundle branch pacing system with automatic AVI optimization was developed, with 0.03 suitable for ε. Accordingly, it was proposed to develop a single-left bundle branch pacing system for a three-chamber pacemaker to automatically optimize AVI based on the RA–RV interval.The pacing system was composed of (1) an algorithm to derive the right atrial-right ventricular (RA–RV) interval based on the atrial-interatrial phase; (2) optimized LUBBPε ; and (3) the algorithm to optimize the pacemaker AVI based on the RA–RV interval with AVI (n) = RA(n) − RV(n) interval × LUBBPε. The regression equation of the RA–RV interval was derived based on the AS–AS interval: RA(n) − RV(n) interval = a + b[AS(n − 1) − AS(n)] interval, and the optimal AVI based on the RA–RV interval can be automatically calculated according to the optimized ε , namely, AVI(n) = RA(n) − RV(n) interval × LUBBPε.① the atrial electrode was used to detect the (A) wave, with AS used as the starting point for the lower limit rate interval (LRI) . When the rate changed by one level (5 beats/min), the AS–AS interval changed by one level (77 ms) (S101). ② The pacemaker program automatically extended AVI to 400 ms (S102). ③ Ventricular sensing (VS) was generated by ventricular electrodes, and AS-AS and AS-VS [namely right atrial sensing and right ventricular sensing (RAS–RVS)] intervals were measured (S103), that is the RA–RV interval corresponding to the A–A interval. A total of 15 points were collected up to the LRI . ④ An algorithm was established to derive the RA–RV interval from the AS–AS interval: RA(n)–RV(n) interval = a + b [AS(n-1)-AS(n)] interval . This equation can achieve an automatic calculation of the corresponding RA–RV interval when the A–A interval alters (S104). ⑤ The default LUBBPε of CRT was 0.66 (S105) with automatic AVI optimization based on the RAS–RVS interval, with the default first level of 0.03. ⑥ LUBBPε can also be set according to the empirical value after system implantation. If necessary, an individual optimization of the optimal LUBBPε (S106) can also be considered. ⑦ The AVI was extended to the intracardiac map to show VS (S107). ⑧ The AS-VS intervalwas measured (S108), acting as the RA–RV interval corresponding to the AS-AS interval ⑨ Echocardiography was optimized, and ε was titrated every 0.03 level with the default value of 0.66 as the baseline (S109). ⑩ When the ε was optimized to the maximum AVVTI and LVEF and the minimum MRA, the optimized LUBBPε was programmed into the pacemaker (S110). The regression equation of the RA–RV interval was derived from the AS-AS interval: RA(n)–RV(n) interval = a + b [AS(n − 1)  − AS(N)] interval, and the optimal AVI based on the RA–RV interval can be automatically calculated according to the optimized ε , namely, AVI (n) = RA(n)  − RV(n) interval × LUBBPε (S111). The algorithm for automatic AVI optimization of a single left bundle branch of a three-chamber pacemaker based on the RA–RV interval to realize CRT can be summarized in the following schematic figure  the left ventricular electrode being located in the left bundle branch area, constituting the normal conduction system of the heart; (2) the normal right ventricular excitation being transmitted to the good fusion of left ventricular pacing excitation. Echocardiography is frequently adopted to estimate LVEF but can also evaluate mechanical dyssynchrony of the heart, providing significant evidence for atrioventricular, interventricular and intraventricular dyssynchrony. Compared with ECG, the visual representation of the cardiac systolic process and noninvasive haemodynamic function assessment can contribute to more accurately assessing the severity of systolic dyssynchrony, which can help to better screen patients meeting the indications of CRT and apply to the optimization of CRT during follow-upHowever, the adaptive CRT algorithm is rooted in conventional CRT, in which LV electrodes are generally implanted in the lateral or posterior veins of the left ventricle, yielding an AVI equal to 70% of the native AV interval. Because the LV electrode of LBBP is implanted below the point of LBB block and located in the conduction system of the heart, the ratio of the optimal AVI to the inherent AV interval will change, but the specific value remains unproposed. LUBBPε = 0.66 ± 0.06 was defined as the ratio of optimal AVI to intrinsic AVD (optimized AVI to RAS–RVS). The results illustrated that CRT can be achieved by optimizing AVI based on the RAS–RVS interval in a three-chamber pacemaker with single left bundle branch pacing, with the optimal AVI reaching 66% of the RAS–RVS interval. Based on the current V–V interval program of three-chamber pacemakers, one step per 10 ms, a three-chamber single left bundle branch pacing system with automatic AVI optimization was developed. Accordingly, it is proposed to develop a single left bundle branch pacing system for a three-chamber pacemaker with the capability to automatically optimize AVI based on the RA–RV interval, with the physiology of the atrioventricular node and defibrillation function retained, and perform defibrillation function in the event of ventricular tachycardia or ventricular fibrillation. Therefore, in the future, a three-chamber pacemaker can be developed and applied to a single left bundle branch pacing algorithm, which can not only realize automatic interval optimization but also ensure the safety of patients, showing obvious significance and application value in the treatment of HF.The three-chamber pacemaker for single left bundle branch pacing can achieve cardiac resynchronization therapy based on right atrial and right ventricular interval, with the optimal AVI to be 66% of RAS–RVS interval.


Despite the evolution of drug therapy in pulmonary arterial hypertension and the more aggressive treatment approach according to the guidelines, patients continue to have unacceptable mortality rates. Furthermore, specific drug therapy alone in chronic thromboembolic pulmonary hypertension also does not seem to have any beneficial impact on survival. As the function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension, the treatment strategy should focus on modifying factors involved in RV dysfunction. Although some previous reports demonstrated that the survival of patients with pulmonary hypertension was associated with mPAP, nevertheless, mPAP is still not considered as a target of therapy. There are many examples of effective mPAP lowering with early and aggressive drug therapy in pulmonary arterial hypertension, or with interventions in chronic thromboembolic pulmonary hypertension. This effective mPAP reduction can lead to reverse RV remodeling, and thus, improvement in survival. In this article, the importance of mPAP lowering is stated, as well as why the change of our current strategy and considering mPAP reduction as the target of therapy could make pulmonary hypertension a chronic but not fatal disease. Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death in a rather short period of time if left untreated. Another form of severe precapillary pulmonary hypertension (PH), a progressive pulmonary vascular disorder also resulting in right heart failure and death, is chronic thromboembolic pulmonary hypertension (CTEPH), which is considered a complication of pulmonary embolism. These two forms of precapillary PH may share similar pathological changes in the distal pulmonary vasculature, including the intimal thickening and remodeling of pulmonary resistance vessels, eccentric intimal fibrosis, intimal fibromuscular proliferation, and plexiform lesions . BesidesWhile the first classification of PH was proposed in Geneva  in 1973,The 2022 ESC/ERS PH guidelines  have recMany etiologies are considered responsible for the evolution of PH, but they all share the same underlying mechanism of elevated pulmonary arterial pressure resulting in an increase in right ventricular afterload. This increase in afterload results in a spectrum of mechanical and biochemical changes, both adaptive and maladaptive, that may lead to the syndrome of right heart failure.Right heart failure is the predominant cause of death in PAH patients , and theThe RV is physiologically coupled to a high-compliance, low-resistance pulmonary circulation as a single cardiopulmonary unit, and low pressure is sufficient to pump the blood to the lungs for oxygenation. The RV seems to adapt better to changes in volume rather than pressure, and thus, afterload is a primary determinant of normal RV function; minor increases in afterload can cause significant decreases in RV stroke volume and, therefore, right ventricular ejection fraction .The increase in pulmonary vascular resistance (PVR) results in an increase in RV wall stress, which is a crucial driver of RV changes from pressure overload. As pulmonary artery (PA) pressure rises, the pulmonary circulation becomes a high-pressure, high-resistance system, like systemic circulation, which adds excessive load to the contracting RV, altering the RV-PA coupling. As vascular pathology in pulmonary hypertension subsets leads to a chronic increase in afterload, the RV has to adapt by hypertrophy and a compensatory increase in contractility to keep the RV-PA coupling constant. Especially in precapillary forms of PH, the vascular disease progressively deteriorates, intensifying the afterload mismatch; the RV dilates in an effort to maintain stroke volume by virtue of the Frank–Starling law, and its contractility becomes insufficient to support adequate function, leading to RV-PA uncoupling.End-systolic elastance is a load-independent measure of contractility, whereas vascular load (RV afterload) is determined by the arterial elastance. The ratio between RV contractility (end-systolic elastance) and RV afterload  describes the concept of RV–PA coupling. In physiologic conditions, the Ees/Ea ratio is between 1.5 and 2, allowing the RV flow output to have a minimal energy cost and optimal RV-PA coupling . This raDoes long-standing PH cause truly irreversible damage in the RV? The importance of mPAP reduction is also evident from the fact that even in the very late stage of the disease, RV function could be restored if, hypothetically, mPAP could be normalized. The best proof for this consideration comes from transplanted patients, where almost any RV recovers within a few weeks after lung transplantation, regardless of the degree of pre-transplant dilatation and dysfunction .RV dysfunction in PH is the major determinant of mortality; improved or normalized RV function after our therapeutic interventions in PH could lead to effectively better survival. The devastating forms of PH, especially if left untreated, are PAH and CTEPH. Early and mainly effective therapeutic interventions in these two forms of PH have been proven to confer a beneficial impact on survival by reversing the remodeling of the RV, but how feasible is the normalization or near normalization of mPAP or PVR in such PH patients?The management of PAH has substantially improved in the last decade. An expanded understanding of PAH pathophysiology led to advances in targeted drug therapy, targeting the nitric oxide (NO), endothelin-1, and prostacyclin pathways (prostaglandin I2) (PGI2). There are currently several drugs available targeting these pathways, including phosphodiesterase-5 inhibitors (PDE5is) such as sildenafil and tadalafil and the soluble guanylate cyclase (sGC) stimulator (Riociguat); endothelin receptor antagonists (ERAs) such as ambrisentan, bosentan, and macitentan; and Prostacyclin class agents. Prostacyclin agents are administered intravenously, subcutaneously, and by inhalation. Recently, oral selective IP prostacyclin receptor agonists, Selexipag and Ralinepag, are available for non-high-risk patients.ERAs and PDE5is are routinely used as an initial combination therapy for the majority of PAH patients. Parenteral prostanoids are predominantly administered to high-risk patients. The sGC stimulator Riociguat and the oral prostacyclin receptor agonist Selexipag have been recently used during patients’ follow-up when low-risk status is not achieved. Initial or sequential combination therapy has become a widely adopted treatment strategy in PAH, simultaneously targeting more than one of the signaling pathways implicated in disease progression. The latest guidelines highlight the early administration of parenteral prostanoids for intermediate–high-risk patients during their follow-up [As PAH remains an incurable condition with a high mortality rate despite the use of PAH-specific drugs targeting the three pathophysiological pathways of the disease, novel agents are currently in phase 3 development, such as sotatercept. Sotatercept acts as a ligand trap for members of the transforming growth factor (TGF)-β superfamily, thus restoring balance between growth-promoting and growth-inhibiting pathways.The significance of lowering PAP in guiding pharmacotherapy has not been widely described so far. In patients with PAH who are responders to vasodilator challenge, high-dosage calcium channel blockers can achieve an impressive reduction in mPAP (239%) and PVR (250%) with the best long-term survival  and, conAs combination therapy targets multiple pathophysiological pathways, it is considered the standard of care in PAH, and initial oral combination therapy is recommended for non-high-risk patients. Studies with oral combination therapy have shown a statistically significant reduction in mPAP and PVR compared to oral monotherapy, but this reduction is arithmetically modest. In a retrospective analysis of the real-world clinical data of 97 patients with newly diagnosed PAH, the initial dual oral combination treatment with an ERA plus a PDE-5 inhibitor resulted in a mean mPAP reduction of <10 mmHg . In anotSimilar findings were provided by the OPTIMA study, where the combination of macitentan and tadalafil led to a mean reduction in mPAP of 7.8 mmHg . FinallyEpoprostenol was the first drug approved for PAH and may still be the most effective in lowering mPAP and PVR, and consequently improving survival. Epoprostenol is known to be the most potent drug among all the PAH-targeted drugs. In a pilot study with upfront triple combination therapy including epoprostenol, mPAP decreased by 32% and PVR by 71%. Furthermore, the survival rate after 3 years of follow-up was 100%, even though the dose of epoprostenol was low (<20 ng/kg/min) . In a stp < 0.05).It is crucial to act as soon as possible with the goal of achieving near-normal hemodynamics before lesions to the pulmonary arterial tree become irreversible. This statement is supported by studies from Japan, where the early use of epoprostenol is common practice. Tokunaga et al.  reportedAll the aforementioned observations show the magnitude of mPAP lowering for improving the outcome of PAH patients. A pulmonary artery pressure-directed multi-drug approach for PAH may reverse right heart remodeling and limit progression, or even reverse pulmonary vascular disease . The majCTEPH is a vascular disorder characterized mainly by a mechanical component due to the obstructive lesions in the pulmonary artery tree caused by organized fibrotic thromboembolic material and variable small vessel disease due to the remodeling of small muscular pulmonary arteries. In CTEPH, the level of mPAP, among other parameters, is a crucial determinant of survival . It is oIn three randomized placebo-controlled trials with bosentan , maciten−5 identified those patients as being at a higher risk of death because of CTEPH. The reduction in afterload parameters also translates into a complete recovery of right and left ventricular geometry soon after PEA, and this right ventricular reverse remodeling is not limited by pre-existing ventricular size, shape, or function before correction [For patients with surgically accessible disease, pulmonary endarterectomy (PEA) is the standard of care, as it is potentially curative. This surgical technique focuses on the mechanical component of the disease by removing obstructive, adherent chronic thromboembolic lesions from within the pulmonary vascular bed. Postoperative hemodynamics becomes normal or near normal in most patients after PEA. As shown from the University of California, San Diego  database including 1500 patients, mPAP can improve markedly following PEA (from 46 to 26 mmHg) . A similrrection . These arrection .Balloon pulmonary angioplasty (BPA) has become an established treatment for selected patients with inoperable CTEPH or persistent/recurrent PH after PEA, improving hemodynamics, right heart function, and exercise capacity , and likA systematic review confirmed the beneficial effect of BPA on several echocardiographic and cardiac MRI indices as the result of RV remodeling and in accordance with hemodynamic improvement . In a meAll these lessons from drug therapy or transplantation in PAH patients and the invasive treatment of CTEPH give us a common conclusion: the rigorous lowering of mPAP is feasible, and this should be the target of therapy. Functional parameters such as the 6MWD or WHO class are very important for assessing risk, but patients will still die if we do not focus on the RV. We now have a lot of proof of how and what can reverse the remodeling of the RV, and this should be the guide for changing our therapeutic strategy. Aggressive initial combination therapy including parenteral prostanoids under regular clinical and imaging follow-up should be the treatment strategy to enable right ventricle reverse remodeling, leading to remarkable hemodynamic amelioration. Moreover, pulmonary artery pressure-directed multi-drug therapies in PAH may reverse pulmonary vascular disease, so the near normalization or normalization of mPAP can be the target of therapy. Further studies are needed to validate mPAP as a primary endpoint in PAH drug trials, and new drugs targeting other pathophysiological pathways could be, in the future, more effective in contributing to a better survival rate.