Short-term mechanical support by veno-arterial extracorporeal membrane oxygenation (VA ECMO) is more and more applied in patients with severe cardiogenic shock. A major shortcoming of VA ECMO is its variable, but inherent increase of left ventricular (LV) mechanical load, which may aggravate pulmonary edema and hamper cardiac recovery. In order to mitigate these negative sequelae of VA ECMO, different adjunct LV unloading interventions have gained a broad interest in recent years. Here, we review the whole spectrum of percutaneous and surgical techniques combined with VA ECMO reported to date. In post-cardiotomy, post heart transplantation and medical VA ECMO indications, including refractory cardiac arrest, concomitant IABP has been considered to be an independent predictor of improved survival and facilitates weaning from VA ECMO.812 Therefore, some authors have advocated the use of an IABP for all patients on VA ECMO, although this strategy has not universally been agreed upon.11 Recent clinical data are conflicting and partly contrast this notion for post-cardiotomy failure, infarct-related shock and other clinical settings based on extensive analyses that do not unequivocally support the routine combination of VA ECMO and IABP as a clinical standard,1315 whereas another recent analysis favors its application and suggests a survival benefit.16The intra-aortic balloon pump (IABP) has been used as an adjunct to VA ECMO for almost two decades and in more than 2,500 patients reported in the literature , smaller LV dimensions and less pulmonary edema on chest x-ray.30 This may not only have a beneficial effect on pulmonary edema, which is thought to complicate at least 30% of VA ECMO treatments, but translate into improved prognosis, even after successful bridge-to-bridge long-term LVAD strategies.29 In summary, the LV unloading effect of an IABP during VA ECMO is rather limited and the PCWP decrease has been reported to reach maximally 5 mmHg, which is supported by clinical experience and computer simulations .24From a theoretical perspective, the introduction of an IABP during VA ECMO could be expected to reduce the mean systemic impedance, systolic pressure and peak LV wall stress by 10-15%25 . Therefo®  is a trans-aortic LV assist device designed as a catheter-based, micro-axial impeller pump that provides continuous blood flow from the LV into the ascending aorta. The 2.5 device provides up to 2.5 L/min blood flow and is intended for percutaneous short-term mechanical support in cardiogenic shock,31 but may lack sufficient blood flow in patients presenting with profound cardiogenic shock, when multi-organ failure is impending and mechanical ventilation is required.33The Impella® 2.5 and the larger CP device have been reported in a number of adult cases  as adjunct to peripheral VA ECMO in order to unload the LV,35 representing the second largest clinical experience as LV unloading intervention during VA ECMO following the IABP. All available Impella® devices for LV support, i.e., 2.5, CP and the surgical 5.0 device have been combined with VA ECMO and revealed a clear reduction of right atrial pressure, PCWP, LV volumes and pulmonary edema in adults .7The Impellan adults  and, als3840 The favorable effect of such a left-to-right shunt on LV decompression and LV loading conditions has been reported to be significant in neonates,41 children3842 and adults,43 as supported by experimental data7 . Alternatively, a dedicated percutaneous device can be used to create well-defined sizes of the atrial septal defect,45 allowing trans-catheter exchange of the device as well as replacement with a definite closure device when not needed any longer.46 It should be realized that atrial septostomy has been reported as one of the first LV unloading techniques during VA ECMO, but remains technically demanding and experience is largely confined to specialized centers and pediatric patients41 .With an atrial septum bulging from left to right, as visualized on the echocardiogram and indicating higher left-sided than right-sided filling pressures, it is tempting to unload the LV by creating an atrial septal defect.al data7 . Yet, it4749 and adults5052 and has, as the atrial septostomy, already been reported in the 1990s53 . It is understandable that the LV venting effect of a cannula in the left atrium is very comparable to an atrial septostomy, as described above. Yet, the blood flow drained to the venous side of the ECMO circuit importantly depends on the sizing of the cannula and tubing51 and flow can potentially be controlled by a separate pump and, also, temporarily be clamped during weaning. In practice, it seems that using a 22F cannula can offer a potent, yet variable degree of LV unloading with a PCWP reduction ranging between 4 mmHg and 17 mmHg.52 If the draining cannula is advanced through the mitral valve into a non-ejecting LV, ventricular drainage will assure circulation of blood in the LV cavity and decrease the risk of flow stagnation and cavity thrombosis. Alternatively, the percutaneous route can also be used to access the LV via a trans-aortic catheter, as proposed in experimental and clinical studies in a very limited number of cases via an axillary or femoral artery approach5456 . An indirect technique using a trans-pulmonary artery catheter can be adopted for LV venting, which is based on experimental findings58 and clinical studies in children and adults.5961 It is important to realize that pulmonary artery venting may, theoretically, result in decreased flow in the pulmonary circulation, resulting in ischemia of the lung and, therefore, implicates close monitoring of pulmonary artery flow and/or end-tidal CO2.62A percutaneous approach to vent the LV by cannulation via the interatrial septum has successfully been applied in children6367 Although, the experience reported in the literature is relatively limited , this might not hold for the regular practice of the technique in selected cardiothoracic surgical centers.A direct surgical approach to unloading the LV requires an apical vent or a venting cannula introduced via the right superior pulmonary vein or, exceptionally, the pulmonary artery, which requires sternotomy or thoracotomy, although minimally invasive approaches have been suggested.supplemental Table 1 and supplemental Figure 1),7 yet remain to carry substantial risks of bleeding.68 In addition, patient care and mobilization in the ICU is challenging.68 Short-term use of venting post-cardiotomy as an adjunct to central arterial cannulation is supported by some authors, despite considerable mortality and complication rates.67Surgical venting techniques use larger-sized cannulae compared to percutaneous approaches, which, in turn, allow improved venous drainage and substantial LV unloading, as supported by clinical experimental data . In this context, surgical adjunct interventions are especially opportune when patients undergo surgical intervention, i.e. thoracotomy or sternotomy, while the role of percutaneous pulmonary artery or trans-aortic LV venting is unclear, as the reported experience is very limited so far .Bridging cardiac failure with VA ECMO is challenging and the potential for short-term myocardial recovery will largely depend on the underlying disease and its individual manifestation. Yet, optimal clinical management remains a mainstay of VA ECMO support. Therefore, it should be realized that LV overload during VA ECMO has an estimated incidence of up to 70% of cases and may significantly impact on survival.5 mmHg24 . When moentions7 (suppleme65 increasing spontaneous echo contrast “smoke” and LV thrombosis.2673 An over-distended LV exposed to high myocardial stress, strain, work and oxygen consumption, as well as reduced coronary blood flow, will likely be unable to recover. Pulmonary edema may primarily occur as a consequence of high LV filling pressures, but systemic inflammation mediated by shock and impending multi-organ failure, as well as blood contact to artificial extracorporeal surfaces, may contribute. In this context, acute lung injury has been shown to significantly impact on prognosis in patients receiving VA ECMO, even after successful bridge-to-bridge therapy.6This LV overload situation may also deteriorate into a life-threatening accumulation of interrelated cardiopulmonary complications, cumulating in pulmonary hemorrhage,75 In general, repeated echocardiograms, assessment of intra-cardiac filling pressures and monitoring of pulmonary edema are imperative on a daily basis. Yet, the exact indication, timing and LV unloading strategy, i.e. percutaneous or surgical, should further be clarified in clinical studies. In addition, it has recently been demonstrated that the acute hemodynamic effects of all interventions detailed in this review can be simulated in computer models76 (76 These models await further clinical validation and it remains to be determined whether clinical decision-making in individual patients on VA ECMO can be improved by patient-specific cardiovascular computer modeling incorporating VA ECMO and other cardiac mechanical support modalities in real time and at the bedside, which is technically already possible.76Detailed clinical assessment of LV overload may be cumbersome, since its biomechanical impact on the failing myocardium may not be well-represented by standard clinical diagnostics.VA ECMO can provide rapid and adequate cardiovascular support in patients with severe cardiogenic shock. Yet, the occurrence of LV overload during VA ECMO support frequently threatens its clinical success and should, therefore, be treated promptly. Here, we review the whole spectrum of adjunct percutaneous and surgical interventions that have successfully been used in clinical practice to unload the LV. It remains a clinical challenge to foresee which patients will benefit from adjunct interventions as they carry inherent procedural risks and it can be extremely cumbersome to predict the expected degree of LV unloading when intervening in an individual patient.Click here for additional data file.Supplemental material, Supplemental_Material_794112 for Left ventricular unloading during veno-arterial ECMO: a review of percutaneous and surgical unloading interventions by Dirk W. Donker, Daniel Brodie, José P.S. Henriques and Michael Broomé in Perfusion


Porcine tricuspid valve (TV) (n = 3) was extracted and incorporated into a patient-specific silicon right ventricle (RV) emulating severe FTR, on which Kay repair was subsequently performed. TV area metrics and RV hemodynamic assessment by means of stereo-scopic particle image velocimetry were quantified in both FTR and post-repair conditions. Bicuspidization led to significant increase in cardiac output although the overall increment due to this approach alone was generally small, possibly due to existence of residual TR and the large reduction in TV opening area. Kinetic energy and viscous loss levels were increased post-repair, especially during diastolic filling. Main vortex structures generally maintained post-procedural. However, there was enhanced swirling motion in larger RV domain. Although this might reduce mural-thrombus risk, the relatively more complex vortex phenomenon likely resulted in elevated viscous loss observed and may potentially impact long-term adaptation. The RV hemodynamic alteration after tricuspid repair could be used to predict the success of these future transcatheter solutions.There has been a resurgence of interest in the treatment of severe functional tricuspid regurgitation (FTR) due to the awareness of its poor outcomes and potential percutaneous therapies. Kay bicuspidization has been adapted in percutaneous therapies but its clinical outcome remains uncertain. The present study evaluates the efficacy of Kay repair in a novel  Severe TR can contribute to right heart failure and increased mortality rate2. In clinical practice, more aggressive FTR management has been recommended after realisation of its progressive nature and poor prognosis3. Especially, the evolving transcatheter technology has allowed the implementation of different surgical repair and replacement therapies by percutaneous approach. However, it remains a great topic of debate regarding the timing, diagnosis and the choice of FTR treatment4. One of the common FTR surgical treatment options is Kay bicuspidization repair, in which the 2 points at annular region along the posterior leaflet is apposed together by sutures, essentially plicating the posterior leaflet5. This leads to a double-leaflet configuration formed by the anterior and septal leaflets, thus the name “bicuspidization”. This technique is of special interest to the interventional community as it is a method of repair adapted into future percutaneous repair technology.The most common mechanism of clinically relevant tricuspid regurgitation (TR) is functional TR (FTR) in which right ventricular (RV) enlargement and/or tricuspid annular (TA) dilatation result in TV malfunction despite the intact TV apparatus6. There are benefits in studying such flow patterns; e.g., flow alteration after different therapies could provide an early surrogate for cardiovascular outcomes7 and potentially be a therapeutic target or assessment tool. While numerous studies have looked into the LV flows, those done on the RV are extremely limited. Compared to the left ventricle, the RV has a more irregular geometrical shape, is an asymmetric structure with more complex TV morphology. This makes in vivo imaging access more challenging and computational modelling susceptible to certain sources of errors. To date, a few in vivo11 and in silico13 studies have looked into the details of physiological RV flow, and there is yet no attempt to quantify RV hemodynamics after different surgical procedures such as those done on atrio-ventricular valve.However, alteration of the natural TV apparatus by bicuspidization repair might alter RV fluid dynamics and energy behaviour. Many studies have demonstrated better hemodynamic and energy behaviour associated with physiological vortex and flow patterns compared to other pathologies or proceduresex vivo mock circulatory system was set up to investigate the three-dimensional (3D) RV flow by stereo-scopic particle image velocimetry (PIV). Hemodynamic characteristics and energy parameters inside a patient-specific silicon RV model, which incorporated an extracted porcine valve, were analyzed. Two scenarios were investigated: (i) severe FTR, and (ii) after TV bicuspidization repair. In addition, quantification of different TV area metrics was performed. To the best of our knowledge, this is the first attempt to characterize the RV hemodynamics after any TV repair therapy.In this study, a novel 14. The RV was modified in order to include a circular circumferential track to be fitted with TV annular ring  in FTR state and (ii) after bicuspidization repair are referred to as group (a) and group (b), respectively.A thin flexible Tygon tubing was sutured along the tricuspid orifice, preserving the natural shape and dimension of the TV Fig. . Subsequ5. In summary, the posterior leaflet was obliterated by plicating the annulus along this leaflet. 5–0 surgical sutures were used to tighten and secure both sides of the annulus together as depicted in Fig. Due to the severe dilatation of both RV and TV annulus, the valves in FTR state exhibited severe regurgitation. As seen in Fig. 14. The system configuration was designed in order to allow optical access and laser illumination in compatibility with stereo-scopic PIV  were measured using clamp-on flow sensor . RV pressure was recorded using a pressure catheter . In this study, the simulator was calibrated to emulate severe FTR condition, characterized by elevated RV pressure, more retrograde flow, and mean CO of 3.9 L/min. Calibrated hemodynamic waveforms for Valve 1 are depicted in Fig. 3, refractive index of 1.5 and mean diameter of 20 µm. Particles on the plane of interest were illuminated with a laser sheet emitted from a 15 Hz Q-switched, pulsed Nd:YAG laser source . The thickness of laser sheet was kept at ~3 mm. Two synchronized CCD cameras  were used to acquire 3D velocity components of the flow  with density of 1.03 g/cm19. Measurements were then repeated for 14 different time points in a cycle.To construct a volumetric flow velocity field, PIV was measured at 22 parallel planes along the long-axis of RV, spaced 3 mm apart. The PIV measurement time-points were phase-locked by synchronization with the trans-tricuspid flow waveform, such that recording was triggered at a particular time instance during a cardiac cycle. 150 measurements at each time instant were found to be sufficient to obtain statistical convergence of a stable velocity vector map2. Post-processing of the derived velocity vector field was performed with built-in median filters and smoothing schemes in Davis 8.3.1 software. The flow velocity field was then interpolated by Kriging algorithm to yield a full three-dimensional visualization and assessment.To derive the 3D velocity field from particle images, stereo cross-correlation was performed with Davis 8.3.1 . Multi-pass iteration scheme with decreasing interrogation window size was used, resulting in the final interrogation window size of 64 × 64 pixels with 50% overlap. This method yielded one velocity vector for every grid area of 2.4 × 2.4 mmThe performance of the valves before and after surgical repair was recorded in both ventricular view and atrial view over a cardiac cycle. Image processing by ImageJ was then performed at the peak opening instant and peak systolic instant to quantify the TV annulus area, TV opening area , and TV regurgitant area  Fig. .Figure 5Mean kinetic energy (MKE) was obtained from the mean velocity component at every spatial point in the RV at each time-step as follows:ρ (kg/m3) is the density of the working fluid, Where 20. Viscous dissipation function Φv which represents the rate of viscous energy dissipation per unit volume was computed as:Viscous dissipation energy loss (VEL) is the irreversible mechanical kinetic energy loss due to frictional forces, mainly in the form of thermal energyνi (m/s) is the velocity component along the i spatial direction, xi is the unit vector along i direction, ∇.ν is the divergence of the velocity field, and δij is the Kronecker delta. Subsequently, the volumetric rate of VEL at a time instance ELt (Watt) can be derived by integrating Φv over the volume domain:Where μ is the dynamic viscosity of fluid (Pa·s) and Vi is the volume element (m3). Total VEL (J) in a cardiac cycle was then calculated by integrating Where 14. In principle, velocity gradient tensor Q-criterion was used to identify vortical structures in the RV to eliminate the contributions of high shear boundary regionsQ is then defined as:Q > 0. In this study, a small positive value of Q = 0.00012 was selected as the threshold value. Vortex and swirling structures were visualized by plotting the iso-surfaces with Q = 0.00012. To quantitatively assess vortical flows, vorticity magnitude can be computed as the magnitude of the 3D vorticity vector:Vortical structure is identified as regions where rotation rate dominates strain rate, i.e., 21. To calculate principal RSS (PRSS), Reynolds decomposition was conducted to determine u′, v′ and w′, which are the instantaneous velocity fluctuation components in x, y and z directions, respectively. The Reynolds shear stress term across  plane was calculated as: ρ being the fluid density, and i direction.Reynolds shear stress (RSS) represents the momentum transfer due to random velocity fluctuations in a turbulent flow regime and has been used as an indicator for blood damage riskThree principal normal stresses The three potential maximum shear stresses were then calculated as:The largest value among the three computed To quantify the change in overall CO after Kay repair, additional six cases were included in the flow loop experiment. Thus, a total of nine cases were tested in the flow loop, for which the CO was assessed before (FTR state) and after Kay bicuspidization repair. A paired t-test was conducted using R software to determine if the change in CO among the cases is statistically significant. The results of the paired t-test showed that the increase observed in CO following bicuspidization was significant . The CO data for these cases can be found in Supplementary information Table .Flow and pressure parameters of the two main valve groups used for area assessment and PIV experiment are depicted in Table Average MKE inside the RV was plotted over the 14 time-steps in the cardiac cycle for Valve 1 Fig. . Mean vaRegarding viscous energy loss, the general trend and shape of the VEL rate curves typically resemble the MKE plots. One example of VEL rate inside RV over a cardiac cycle  is shown in Fig. Figure As presented in Fig. As seen in Fig. During late diastole, a more planar but incomplete  vortex ring formed past the orifice. Similar to FTR case, the vortical structure formed during early diastole dissipated considerably at the lateral-anterior side. However, part of the septal vortical structure was also dissipated due to the impingement onto the septal wall. As a result, this vortical structure broke into halves (time-points 8 & 9). As the newly formed vortex ring proceeded into RV cavity, the part of previous vortical structures near the posterial wall continued to dissipate, while the other half extended towards the pulmonary outlet. During systole when vortical ring structure could no longer be observed, there was a large volume of vorticity contour near the outlet, in the form of elongated structures that continued to exist into early diastole. Compared to Valve 1a, vorticity contours of Valve 1b showed a more complex evolution behaviour with lots of vorticity residuals which did not belong to any compact vortical structure.Figure At peak systole, scattered flow patterns were found in some RV regions for both valve groups where velocity vectors were not directed towards the outlet Fig. . SpecifiThe mean vorticity magnitude over the whole RV domain as well as Q-thresholded vortical structures were quantified for each time-point and summed over the cardiac cycle. These values were averaged for both groups and are presented in Table 2 for Valve 1a, 27.26 N/m2 for Valve 2a, and 27.23 N/m2 for Valve 3a, whereas these values increased to 32.55 N/m2 for Valve 1b, 53.04 N/m2 for Valve 2b, and 46.14 N/m2 for Valve 3b. Nevertheless, all the values are well below the threshold stated in the literature for blood hemolysis risk21 (800 N/m2).It is expected that the reduced opening area and elevated inflow velocities increase the level of turbulent shear stress. This is supported by our results which showed that bicuspidization repair elevated the maximal PRSS detected inside the RV domain at the peak E-wave time instant for all three cases studied. The maximal PRSS observed at peak E-wave for the FTR valves was 21.66 N/m23. A platelet activation parameter was previously formulated as the integral of shear stress and time24. This concept was subsequently applied to assess the platelet activation tendency of fluid going through high shear regions by estimating the shear stress-time product25. In the present study, the time for a particle moving through the tricuspid orifice with high E-wave inflow velocities was estimated to be <0.0230 s for Valve 1b, <0.0133 s for Valve 2b, and 0.0243 s for Valve 3b. This corresponded to the shear stress-time product of <0.7487 Pa.s for Valve 1b, <0.7041 Pa.s for Valve 2b, and 1.1216 Pa.s for Valve 3b. These values are below 3.5 Pa.s which has been suggested for procoagulant platelet factor 3 release23.It is also known that the platelet activation could be induced by the combination of high shear stress and large exposure timeset al.26 performed different procedural variations of edge-to-edge repair on an ex vivo porcine model of FTR; the outcomes in terms of CO and pressure were found to be strongly dependent on the pair of leaflets grasped as well as the position of clips. Indeed, many of the variations resulted in marginal if not detrimental effects on the CO recovery. Thus, while certain repair techniques can diminish regurgitation and resolve the elevated atrial and venous pressures, their impact on CO recovery might be deemed unsatisfactory.Although bicuspidization was able to correct for TR, the repair also reduced TV annulus area and especially TV opening area substantially. Moreover, bicuspidization alone does not necessarily result in complete eradication of regurgitation Table . The ext30. In the current study, bicuspidization repair enhanced the KE levels of RV in general. Especially, the repair altered the pattern of MKE inside the RV over a cardiac cycle in comparison with that observed in FTR state. While FTR valves exhibited highest KE during systole, similar to that reported for healthy RV31, maximal KE for the repaired valves was shifted to early diastole. This implied that the physiological flow pattern was not restored with repair. The prominently increased diastolic MKE observed post-repair is likely attributed to the abnormal high velocity inflow pattern which is not the case in healthy RV or in FTR pathology. As the valve opening area is considerably reduced, blood is subjected to higher velocity over a smaller inflow area – resembling forward stenosis to some extent. The peak velocity of FTR valves in diastole ranged from 0.43 m/s to 0.61 m/s. After bicuspidization repair, this value was markedly increased up to 1.00 m/s. In practice, it is not uncommon to record peak trans-tricuspid velocity exceeding 1 m/s in tricuspid stenosis32. Theoretically, KE is defined as the work needed to accelerate a given mass of blood from rest to its velocity33. Given that the CO did not differ much after repair, it is speculated that higher KE levels post-repair might indicate that greater work was necessary to transfer the fluid from inlet to outlet. Indeed, the large increase in VEL levels post-repair also implied that higher degree of the work done to accelerate the fluid was lost to heat inside the RV after repair, as compared to the energy loss observed before repair. Nevertheless, it is also noted that in this scenario, the RV model exhibited severe dilatation with reduced contraction, thus an optimal flow pattern with lower energy expenditure yet higher output might not be possible with any other treatment approaches. Increasing number of studies have proposed MKE as a potential cardiac marker and driver in disease progression or morphologic changes. Altered intraventricular energy levels have been suggested to influence the pressure gradients and the subsequent myocardial remodelling27. Moreover, any subtle inefficiency in energy expenditures might contribute to cardiac failure over extended time28. In this perspective, it is important to quantify MKE under different pathologies and procedures. Further studies relating the MKE changes and clinical consequences are necessary and could be utilized to guide future medical and surgical interventions.Prior studies have demonstrated the altered ventricular KE levels and patterns in pathological conditions compared to healthy controls37. Moreover, when the dilated RV typically loses its normal contractibility in pathological situations such as severe FTR, the possible contribution of more dominant vortex and helical structures to fluid transfer could become particularly relevant. On the other hand, stronger vortical motion accompanied by increased irregular structures and vorticity residuals could imply more chaotic interactions and loss of energy due to viscous dissipation and turbulence. Various studies have demonstrated the correlation between disrupted natural vortex patterns and elevated viscous energy loss38. Likewise, the current results showed substantial increase in VEL inside the RV after repair, especially during diastolic filling, implying the increased viscous loss associated with more irregular vortex structures. In addition, the modified vortex pattern might subject the RV to altered shear stress levels with increased regions exposed to elevated shear, potentially leading to long-term adaptation consequences. In terms of turbulent shear, the repair increased the maximal PRSS observed inside the RV at peak E-wave for all three valves tested. Nevertheless, these values were well below the hemolytic RSS threshold21. Likewise, estimated values of shear-time integral for the repaired valves were below the threshold indicated for platelet activation23. Thus, it is unlikely that blood components would be subjected to noticeable risk of damage due to turbulent shear even after repair.The overall vortex phenomenon was mostly preserved after repair. In general, two vortex rings formed past the valve orifice during early and late diastole and evolved as they propagated into the RV cavity. The perseverance of vortical structures in the RV space as they moved past the tricuspid orifice could be the result of the RV dilatation, leading to more cylindrical expanded configuration. Subsequently, the vortical structures dissipated partly after interaction with RV wall and elongated towards the outlet during systole. This possibly represented the re-organization of vortical structures into the helical patterns as the blood exited through a gradually narrowing pathway. There are, however, some distinctive characteristics between the two valve groups. Post-procedural vorticity contours typically exhibited more isolated vorticity residuals. In addition, vortical cores inside the RV post-repair acquired more irregular structures as compared to the compact and relatively symmetrical nature of those formed inside the RV before repair. Given that the tricuspid orifice was modified to be smaller and more elliptical, along with the transformation of leaflet morphology to be mitral-like configuration, altered inflow dynamics and vortex formation were expected. Quantitatively, bicuspidization subjected RV domain to augmented levels of swirling motions as indicated by vorticity magnitude calculations. Post-procedural vortical structures also took up a larger RV domain as compared to FTR cases. On the one hand, strong circulation in larger RV domain might reduce the risk of mural-thrombus formation40, while significant alteration to complete elimination of vortical structures were observed in other approaches42. In this study, although bicuspidization repair increased viscous loss and led to more irregular vorticity residuals, the main vortex structures were generally maintained. Nevertheless, both FTR and post-repair RV flow domains exhibited non-optimal flow pattern, including the varying extent of regurgitation and recirculation regions during systole. While the use of annuloplasty in conjunction with bicuspidization repair might help in eliminating regurgitation, the influence of further reduced orifice area on hemodynamic parameters and valvular area metrics is unknown and deserves further investigation. Given the reduced RV contractibility along with the dilated RV morphology, attaining the ideal fluid transfer behaviour might be difficult with any strategy.In the LV, preservation of vortex structure have been reported with certain MV repair strategies43. Insulated radiofrequency wires are typically positioned 2 to 5 mm from the base of the posterior leaflet and within the annulus, at the postero-anterior commissure and septo-posterior commissure. Once these wires are through the annulus, pledgets can be advanced over the wires and cinched to the corresponding anatomical sites on the annulus portion. The sutures connecting the two pair of pledgets are then drawn together and locked to plicate the posterior annulus. This approach was applied in first-in-man procedure in 2014 and an early feasibility study is currently ongoing 4. Although feasibility and successful implantation have been shown possible in a number of patients, durable results post-treatment are currently uncertain. Moreover, a ‘partial’ correction of TR could be considered to avoid the hemodynamic burden of acute complete correction of TR to the RV4, although long-term efficacy of this approach remains unclear. Results from the current study imply that complete bicuspidization might lead to some extent of forward stenosis due to the restricted leaflet opening area, potentially limiting the cardiac output recovery. How a partial correction approach could influence the cardiac output and other hemodynamic parameters remains unknown and deserves further research.Currently, transcathether technology is emerging as an attractive treatment option for high-risk patients. Nevertheless, TV interventional therapies are still at its early stages of development compared to other valvular treatments. Among different percutaneous approaches, Mitralign system  can reproduce Kay bicuspidization surgical repair. In summary, the device is used to place pledget sutures by means of a trans-jugular approach44. Moreover, in the setting of severe RV enlargement, the intraventricular septum is shifted leftward45 leading to a more spherical RV configuration. It is also likely that the dynamic motion of the RV would be reduced in comparison to a healthy heart, due to the combination of long-standing RV dilatation and aging factor which is common in severe TR population. Thus, these factors would partly justify the characteristics of the present ex vivo system.The experimental system was subjected to several intrinsic constraints of common mock simulators, including the lack of torsion and strong ventricular wall dynamic motion and the absence of LV-RV interaction. Nevertheless, it has been shown that twisting and rotational motions do not contribute significantly to RV contraction in contrast to the LV47. It has been established in the literature that detection of true pathological regurgitant volume of the TV is not straightforward due to the contribution of closing volume and the fact that the majority of the population has some degree of “physiologic” TR46. In the current system, the flow sensor was clamped onto the plastic tubing upstream of the RV chamber where the TV was housed. Since there was an unavoidable distance between the sensor and the exact location of the valve, the signals received by the sensor seem to mostly reflect the closing volume and might not accurately reflect the regurgitant volume. Hence, the regurgitant flow is not detected without being overshadowed by the closing volume. Other flow measurement methods such as those that can assess directly the regurgitant jet inside the fluid48 might be more useful in this scenario to assess the true TR volume or severity. Hence, trans-tricuspid flow curve was mainly used as a mean for validation of systemic hemodynamic condition rather than a tool to quantify accurate TR volume in the present study.In the present study, the trans-tricuspid flow waveform post-repair was not reported as an indicator for the efficacy of resolving TR. During TV closure, the total amount of back flow was contributed by both the closing volume due to the leaflets closing motion and the pathological regurgitant volume caused by the incomplete coaptation of the leaflets49. Future studies involving more samples and geometrical variations will be conducted to warrant the validity of current findings.The limited number of samples in this study could impose constraint in the validity of results in more clinical situations. Nevertheless, the present study aims to address the efficacy of bicuspidization in a severe FTR scenario which includes all elements of RV dilatation, PM displacements and TV annular dilatation. While the existence and degree of geometrical modification for each of these components might vary clinically, it is expected that severe and late stage of FTR would exhibit all the characteristics addressed in this studyex vivo system did not emulate outflow obstruction, this study only considers cases of severe FTR without pulmonary hypertension.In addition, only Kay bicuspidization approach was investigated in this study. Several other treatments are also common in clinical practice which require further investigations, including annuloplasty, edge-to-edge repair, as well as replacement with prosthetic valves. Furthermore, since the ex vivo right heart simulator by means of stereo-scopic PIV. Results indicated that the repair led to significant increase in cardiac output although the overall increment due to this approach alone was generally small, possibly due to existence of residual TR and the large reduction in TV opening area. The repair elevated kinetic energy of RV fluid especially during diastolic filling. Main flow and vortex structures were generally maintained post-procedural. However, more irregular vortical structures and more isolated vorticity residuals were observed inside the RV after repair. The enhanced swirling motion in a larger RV domain after repair might reduce the risk of mural-thrombus formation and potentially aid in fluid redirection. Nevertheless, the relatively more complex vortex formation led to augmented friction-driven interactions indicated by the observed increase in viscous energy loss, especially during diastolic filling. Further investigations are needed to assess the efficacy of tricuspid repairs in more stages of FTR as well as to link the difference in vortex patterns and energy metrics with potential clinical outcomes. This study provides better understanding of how RV hemodynamic conditions are altered with TV repair which could allow better treatment design and planning in the future.In this study, TV area and RV hemodynamic characteristics before and after Kay bicuspidization repair in a severe FTR situation exhibiting both severe RV and TA dilatations were investigated for the first time in a novel S1


Ventricular arrhythmia storm is a state of cardiac instability characterized by multiple ventricular arrhythmias or multiple ICD therapies within a 24-hour duration. Management of this life-threatening state depends on the reversal of the cause besides either electrical or medical management of the arrhythmia. We report a case of a 54-year-old male who underwent a percutaneous coronary intervention following massive acute myocardial infarction. Afterwards, he developed frequent life-threatening ventricular arrhythmias that required multiple shocks and antiarrhythmic medications. Despite all these interventions, it was very difficult to control the electrical instability, but after overdrive ventricular pacing, the storm subsided and within a few days the case was stabilized. Overdrive pacing is an easy temporary modality to control the resistant arrhythmia following myocardial infarction. Electrical storm is a life-threatening arrhythmia that might occur after myocardial infarction. In severe cases, arrhythmias are resistant to medications and the direct current (DC) shock. Repeated shocks are also injurious to the heart and lead to progressive myocardial inflammation and fibrosis –4. The mA 54-year-old diabetic and hypertensive male patient presented with a central chest pain while sleeping that lasted for an hour. On the ambulance, he became drowsy and developed ventricular tachycardia that was reverted to sinus rhythm by DC shock.On admission to ED (3 hours after the pain), he was in pain and in the physical exam and he was fully conscious and oriented and in distress. Vitals were within the normal limits except for a slightly elevated blood pressure of 150/90. ECG showed normal sinus rhythm and ST elevation in leads V1 to V6 with deep Q waves in the same leads .In the coronary catheterization lab (30 minutes after admission to ED), coronary angiography showed total proximal left anterior descending (LAD) artery occlusion and midleft circumflex (LCX) 80% lesion. The LAD lesion was stented with a DES.After the procedure, he was stable with residual chest pain. Then, 2 hours later, he was found unresponsive with pulseless ventricular tachycardia, and after a single DC shock, he regained his consciousness and his sinus rhythm again .The next morning, he developed asymptomatic sustained ventricular tachycardia that reverted spontaneously to sinus rhythm; then, the telemetry showed multiple premature ventricular complexes (PVCs) and nonsustained ventricular tachycardia (NSVT) . AmiodarAfter two hours, he developed again asymptomatic ventricular tachycardia and IV lidocaine 70 mg bolus was given. Then, relook coronary angiography showed patent LAD stent and small ostial LCX clot that was aspirated.In the evening, he had ventricular tachycardia  with hypThe next day, clusters of ventricular tachycardia triggered by ventricular premature contractions occurred  and requAfter overdrive pacing with a rate of 100, his rhythm was stable with complete suppression of PVCs and no further attacks of ventricular arrhythmias .In the next day, gradual weaning of inotropes and sedations started until it is completely stopped. His rhythm was stable on oral amiodarone 400 mg twice daily and metoprolol 25 mg twice daily in addition to the pacing.After another 24 hours of stable rhythm, the pacemaker was removed and close observation showed no any ventricular arrhythmias . The nexHe was observed in the coronary care unit for 2 days showing hemodynamic and electrical stability. After 2 weeks of discharge, he was seen in the clinic in a good state of health.Electrical storm (ES) indicates a state of life-threatening cardiac electrical instability characterized by clusters of ventricular arrhythmias in a short amount of time. It is defined as the presence of at least 3 distinct episodes of sustained ventricular tachycardia or VF in the last 24 hours. In the patients with an ICD, the most widely accepted definition of the electrical storm is three or more appropriate therapies for ventricular tachyarrhythmias, including antitachycardia pacing or shocks, within 24 hours .Studies have shown that in only 10-25% of patients with the electrical storm, clear precipitating causes were identified . Some imES is a clinical emergency that needs appropriate early management. Initially, antiarrhythmic drugs such as beta blocker and amiodarone are usually used , 8. The Then, beta blockers are very important in the suppression of the sympathetic discharges after the arrhythmias and DC shocks. Propranolol (40 mg every 6 hours) has shown superior efficacy to metoprolol in a trial performed on 60 patients with electrical storm who received amiodarone, and this showed that the time to termination of the arrhythmias was earlier in the propranolol group in addition to lower rate of tachycardia recurrence or ICD discharges and shorter stay in the hospital . There aIn case of failure of medical therapy, radiofrequency catheter ablation of the arrhythmogenic focus is a promising effective method for the management of the ventricular arrhythmia .In the recent European Society of Cardiology's guidelines for the management of ventricular arrhythmias, transvenous catheter overdrive stimulation received a class IIa recommendation, and level of evidence C in case of recurrent ventricular arrhythmia despite the use of drug therapy and catheter ablation is not possible .In our case, we report a state of severe electrical storm following a massive acute myocardial infarction. This arrhythmia persisted despite the frequent DC shocks in addition to amiodarone, lidocaine, and beta blocker therapy. In this life-threatening condition, an early intervention is needed to save life, to prevent the short- and long-term sequelae on the myocardial muscles, and to improve the patient's quality of life. Overdrive pacing is a method utilized to terminate the tachycardia by pacing the patient's heart at a rate faster than the intrinsic rhythm. Pacing the patient's heart at a rate of 100 beats per minute succeeded in controlling the arrhythmia without the need of multiple DC shocks.Kurisu et al.  reportedAdditionally, in the management of the ES, there were other reported management plans. Mulpuru et al.  found thES usually reflects a poor prognosis with higher mortality, increased rate of hospitalization, and negative impact on the quality of life. Also, the electrical cardiac shocks besides their beneficial control of the arrhythmia and their frequency lead to more cardiac damage and progressive inflammation that later end up with cardiac fibrosis and worsening cardiac function , 4.In severe cases of electrical storm that is refractory to the initial management, overdrive pacing is a helpful temporary method in the stabilization of the case and it could be a very important early tool to decrease the mortality in resistant arrhythmia after myocardial infarction.


Left atrial (LA) remodeling has been identified to predict atrial fibrillation (AF) and heart failure. However, the role of LA diameter (LAD) in patients with heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) remains poorly understood.A total of 142 patients including 71 subjects with AF  and 71 ejection fraction (EF)-matched subjects with sinus rhythm (SR) were included in the study. Baseline characteristics and echocardiographic parameters including LAD were compared between both groups as well as among HFpEF, HFmrEF, and HFrEF.P = .03]. LAD was negatively association with left ventricular ejection fraction while positively with Nt-proNP and left ventricular end-diastolic diameter . In ROC analyses, LAD predicted HFrEF among the 3 categories .In receiver-operating characteristic (ROC) analyses, LAD predicted AF in HFpEF, HFmrEF, and HFrEF [area under the curve (AUC): 0.646; In the setting of HF, LAD was higher in AF than in and SR, and predicted AF. Furthermore, LAD was associated with severity of HF in HFpEF, HFmrEF, and HFrEF, and also predicted HFrEF. HFrEF has greater eccentric LA remodeling, whereas HFpEF has increased LA stiffness. LA function is associated with outcome more closely in HFpEF. LA diameter (LAD) is simple, convenient, and commonly used in clinical practice and research studies. LAD is an independent predictor of the occurrence of HF in patients with nonvalvular AF. LA enlargement in AF patients had a greater incidence of HF. To our best acknowledge, the association of LAD with HFpEF, heart failure with left ventricular mid-range (HFmrEF), and HFrEF remains unknown.The left atrium plays a key role in regulating left ventricular filling and cardiovascular performance by reserving pulmonary venous return and augmenting ventricular filling. The increasingly interest in atrial size and function has led to our better understanding of cardiovascular disease. Left atrial (LA) enlargement has been demonstrated to be a predictor of adverse cardiovascular outcomes, such as atrial fibrillation (AF), heart failure (HF), and cardiovascular death. Atrial dilatation is the major marker of left atrium remodeling and promotes the occurrence or maintenance of AF. Any persistent change in atrial structure or function leads to atrial remodeling. Therefore, these structural changes of LA are common in AF as a result of the high prevalence of hypertension, cardiovascular disease, and HF. The majority of data of the AF–HF relationship is based on HFrEF. Recent research showed that AF was progressively more common with increasing ejection fraction (EF), whereas associated with similar clinical characteristics in HFpEF, HFmrEF, and HFrEF. LA enlargement is associated with AF in the general population and ischemic stroke. However, whether LAD correlated with AF in HFpEF, HFmrEF, and HFrEF is poorly understood. Therefore, the aim of the present study was to investigate the relationships between LAD and HFpEF, HFmrEF, and HFrEF as well as AF.The AF is common in HF, and they share common risk factors, affect each other, and together result in a worse prognosis.22.1 Two-dimensional and 2-dimensionally guided M-mode images were recorded from the standardized views. Left ventricular EF (LVEF), left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), interventricular septal thickness at end diastole (IVSd), and the left ventricular posterior wall thickness at end diastole (LVPWd) were also measured.This was a hospital-based single center retrospective cohort study of patients with HFpEF, HFmrEF, and HFrEF. A total of 321 consecutive subjects with HF referred to Wenzhou People's Hospital between August 2015 and March 2018 were reviewed. The patients meeting inclusion and exclusion criteria were divided to AF group and sinus rhythm (SR) group. Meanwhile, the 2 groups have the same subjects with HFpEF, HFmrEF, and HFrEF. All the patients underwent electrocardiogram. AF patients including paroxysmal and persistent were confirmed by 24-hour dynamic electrocardiogram. AF patients without ablation history were included in this study. The criterion and classification of HF were used according to the European Society of Cardiology HF guidelines. In the present study, patients with EF of ≥50% were defined as HFpEF, EF of 40% to 49% as HFmrEF, and EF of ≤39% as HFrEF. Exclusion criterion was as follows: recent acute myocardial infarction, recent stroke, recent acute coronary syndrome, chronic pulmonary heart disease, severe valvular disease, autoimmune disease, inflammatory states, and cancer. Comorbidities on admission were extracted by reviewing discharge letters. Baseline characteristics including age, gender, medical history, and medications, presenting symptoms and signs (including NYHA), a history of smoking or alcohol and laboratory values were obtained directly from the hospital information system. This study complies with the ethics review board of Wenzhou People's Hospital. Due to the retrospective nature of the study, informed consent was waived by the ethics committee. All methods were performed in accordance with the relevant guidelines and regulations. Echocardiographic examination was ensured to be conducted by an experienced echocardiographer based on the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging.2.2P-values of <.05 were considered to indicate statistical significance.The final study population consisted of patients meeting the above mentioned criteria. SPSS 22.0 was used for the statistical analyses. All the data are presented as mean ± standard deviation. Differences in discrete variables were compared among the groups examined by using Chi-squared, the Fisher exact test, or Mann–Whitney tests. The Kruskal–Wallis tests were used of comparison of nonsymmetric continuous variables. Correlations analysis was used to determine the relationships between variables by Spearman rank correlation test. Receiver-operating characteristic (ROC) curve analysis was conducted to identify LAD predicting AF and HFrEF. 33.1P < .001).Of 321, 142 patients met our inclusion and exclusion criteria. About 71 subjects with AF  and 71 EF-matched subjects with SR were included in the study. Clinical characteristics of the 2 groups are summarized in Table 3.2P = .03, Fig. P = .168, Fig. P = .004; regression coefficient: −0.191, P = .023; regression coefficient: 0.357, P < .001). Data also showed there was no correlation of LAD with NYHA Class .In ROC analyses, LAD predicted AF in HFpEF, HFmrEF, and HFrEF with optimal cut-off point above [area under the curve (AUC): 0.646; 3.3P = .017; regression coefficient: 0.225, P = .007, regression coefficient: 0.178, P = .034; regression coefficient: 0.15, P = .076, Table For other risks for HF, LAD were positively with coronary heart disease, prior myocardial infarction and hypertension, but not diabetes , but LAD in HFpEF and HFmrEF was similar . We also found Nt-proBNP in HFrEF was higher than HFpEF ; however, there were no differences between HFpEF and HFmrEF, as well as HFmrEF and HFpEF . ROC analysis showed LAD and NT-proBNP predicted HFrEF among the 3 categories  and HFrEF (LVEF < 50%). To eliminate the effects of LVEF, AF patients and SR patients enrolled in this study were EF matched. Our ROC analysis also showed LAD could predict AF in HF.Atrial dilatation is the major marker of left atrium remodeling. LA enlargement could predict the development of 1st AF. LA area is also a powerful predictor of death or hospitalization among HF patients with predominantly impaired systolic function. Furthermore, LA volume index predicted chronic HF hospitalization and mortality as well as LVEF in patients with coronary disease. 3D LAV >100 mL predicted cardiac deaths and hospitalizations as a result of heart failure among patients with severe LV dysfunction. In the present study, we also found LAD was associated with LVEF. There was a significant correlation with LAD index and left ventricular filling pressure; therefore, LAD directly reflected the left ventricular filling pressure. As was shown in this study, although LAD was not associated with NYHA class because of the subjective assessment factors, LAD was associated with Nt-proBNP and LVEDd.The association of LA enlargement with HF has been well established. LA was accompanied remodeling, apoptosis, myosin isoform expression, collagen matrix turnover, and reduced intrinsic contractility when response to increased loading. In SOLVD Registry and Trials, LAD was associated with increased risk of death and cardiovascular hospitalization. Although ANP levels did not have impact on systemic blood pressure, a recent study showed that after LA appendage exclusion, systemic blood pressure was reduced in patients with AF and history of hypertension. Furthermore, the indexed LAD correlated positively with diabetes mellitus, hypertension, and coronary artery disease. In fact, high blood pressure induced anatomic and hemodynamic changes, which was associated with atrial wall stress, and decreasing left ventricular diastolic pressure, subsequently affecting clinical outcomes in HF. Our data showed LAD was also associated with hypertension. Patients with AMIs followed for a mean of 15 months, higher LA volume index was a powerful predictor of all-cause mortality. AMIs and larger LA volume index was correlated with a higher incidence of chronic HF, increased LV dimensions, and reduced LVEF. The result showed LAD was correlated with coronary heart disease and prior myocardial infarction. In this study, LAD was not associated with diabetes, although diabetes mellitus was independent correlates of LA fibrosis and poor outcomes.,26Several risk factors, such as hypertension, diabetes mellitus, and coronary artery disease contributed to development of HF. LA appendage stores about 30% of ANP, which regulates natriuresis and diuresis. Moreover, HFrEF (LVEF < 0.5) patients had larger LA volumes than HFpEF (LVEF ≥ 0.5). There was no difference in LV mass and LA volume between diastolic HF and systolic HF, but the sample size of this study was very small. In the present study, LAD increased accompanying with decreased LVEF. And LAD predicted HFrEF across the 3 categories.In several studies, LA remodeling has been compared in HFpEF and HFrEF. LA maximal volume and active emptying fraction were greater in systolic HF (LVEF < 0.5) than diastolic HF (LVEF ≥ 0.5).,29Although LAD may less precisely represent the true LA size than LA volume, LAD is still a reliable surrogate. Furthermore, measurement of LAD is more easily conducted than LA volume and has already been included in the routine echocardiographic examination. Despite not wide application, several study also reported that LAD could be used to predict clinical outcomes.In conclusion, in the setting of HF, LAD was higher in AF than in and SR and predicted AF. Furthermore, LAD was associated with severity of HF, and also predicted HFrEF across the three categories. However, it is hard to permit any definite conclusions due to the small sample. Prospective studies with long-term follow-up are required to evaluate the role of LAD in HFpEF, HFmrEF, and HFrEF.4.1The present study has some limitations. The sample size was small. Furthermore, our study was observational study and longitudinal data are necessary to evaluate the role of LAD in HF. Finally, follow-up study should be conducted to elucidate the predictive role of LAD for outcome of HF. All the patients with paroxysmal could not be confirmed by 24-hour dynamic electrocardiogram.The authors thank all the study personnel for their contribution.Data curation: Hao Chen, Xuyong Zhao, Fanhao Ye.Formal analysis: Wenbing Jiang, Yi Wang.Supervision: Ning Zhu.Writing – original draft: Wenbing Jiang.Writing – review & editing: Ning Zhu.Ning Zhu orcid: 0000-0002-7521-6266.


Heart failure (HF) is associated with progressive ventricular remodeling and impaired contraction that affects distinctly various regions of the myocardium. Our study applied cardiac magnetic resonance (CMR) feature tracking (FT) to assess comparatively myocardial strain at 3 distinct levels: subendocardial (Endo-), mid (Myo-) and subepicardial (Epi-) myocardium across an extended spectrum of patients with HF. 59 patients with HF, divided into 3 subgroups as follows: preserved ejection fraction , HF with mid-range ejection fraction , HF with reduced ejection fraction  and a group of age- gender- matched volunteers (N = 17) were included. Using CMR FT we assessed systolic longitudinal and circumferential strain and strain-rate at Endo-, Myo- and Epi- levels. Strain values were the highest in the Endo- layer and progressively lower in the Myo- and Epi- layers respectively, this gradient was present in all the patients groups analyzed but decreased progressively in HFmrEF and further on in HFrEF groups. GLS decreased with the severity of the disease in all 3 layers: Normal > HFpEF > HFmrEF > HFrEF . In contrast, GCS was not different between the Normal and HFpEF  but was, as well, markedly lower in the systolic heart failure groups: Normal > HFmrEF > HFrEF . CMR feature tracking multilayer strain assessment identifies large range differences between distinct myocardial regions. Our data emphasizes the importance of sub-endocardial myocardium for cardiac contraction and thus, its predilect role in imaging detection of functional impairment. CMR feature tracking offers a convenient, readily available, platform to evaluate myocardial contraction with excellent spatial resolution, rendering further details about discrete areas of the myocardium. Using this technique across distinct groups of patients with heart failure (HF), we demonstrate that subendocardial regions of the myocardium exhibit much higher strain values than mid-myocardium or subepicardial and are more sensitive to detect contractile impairment. We also show comparatively higher values of circumferential strain compared with longitudinal and a higher sensitivity to detect contractile impairment. A newly characterized group of patients, HF with mid-range ejection fraction (EF), shows similar traits of decompensation but has relatively higher strain values as patients with HF with reduced EF. An increased preponderance and higher mortality of patients with diastolic heart failure3 warrants improvements towards a more particularized therapeutic approach and follow-up.Heart failure represents worldwide a massive burden and, despite progresses in treatment strategies including medication and cardiac device therapy5. Complexity to the assessment of heart contraction increases when myocardium undergoes pathologic hypertrophic remodeling or develops microvascular dysfunction due to various systemic syndromes such as hypertension, obesity, diabetes or coronary artery disease6.Human heart anatomy is complex, comprising 3 distinct layers of muscular fibers with different angular orientation, starting from a longitudinal distribution toward the endocardium and progressively being interspersed by oblique fascicles with contrary helical orientation from base to the apex and, respectively, by circular fascicles towards the epicardium. This particular architecture is essential to ensure a specific pattern of motility and force generation during the cardiac cycle: descend of the mitral valve plane towards the apex, uniform decrease/increase in short-axis diameter, base to apex twisting/untwisting7. Longitudinal strain is a powerful predictor of mortality in patients with acute8 and chronic heart failure9, overpassing widely used parameters such as ejection fraction (EF) or left ventricular (LV) volumes. Moreover, in patients with myocardial infarction (MI), reduced myocardial strain values are quantitatively correlated with the extent of MI and respectively, with the incidence of adverse event and prognostic10.Being less influenced by haemodynamic forces and tethering effect of adjacent segments, strain rate imaging holds the promise to render an adequate evaluation of the spatial contractility parameters  measurable at each voxel level over the cardiac cycle11, with an excellent inter- observer, intra- observer agreement and high inter- study reproducibility13.CMR feature tracking (FT) technique provides information about myocardial mechanics. Myocardial strain and strain rate are obtained from the analysis of conventional balanced steady state free precession (bSSFP) cine imagesThe purpose of this study was to assess the longitudinal and circumferential strain at the level of 3 distinct myocardial layers  in HF patients and correspondent age- and gender- matched normal subjects and give an account of the variability of dimension range and discriminating diagnostic ability of these parameters.14 into 3 groups, as follows: (1) patients with HF with preserved ejection fraction (HFpEF), where EF ≥50% but diastolic dysfunction is present  and plasma levels of NT-proBNP >125 pg/mL, (2) patients with HF with mid-range ejection fraction (HFmrEF), where EF = 40–49% and similar additional criteria are present, (3) patients with HF with reduced ejection fraction (HFrEF) where EF < 40%. Exclusion criteria were: more than trivial MR, uncontrolled hypertension, atrial fibrillation, incompleteness, reduced quality or presence of artifacts in the images acquired. Inclusion of patients took into account a match for age and gender distribution between the groups. For comparison a fourth, similar group of age- and gender- matched volunteers have been recruited, and underwent an identical protocol with the HF subjects. The final numbers of subjects included, demographics and descriptive statistics of the parameters took into consideration are shown in Table The study was approved by the Ethics Committee of the Charité-University-Medicine in Berlin, complied with the Declaration of Helsinki and was registered at the German Register for Clinical Studies (DRKS) (registration number: DRKS00015615). All individuals were fully informed about the aim, rationale and detailed protocol of the study (subject information leaflet) and consequently written informed consent was obtained before participation. For this study, we included prospectively, patients with a diagnosis of HF who were subdivided according to recent guidelines3 and 50 phases per cardiac cycle in accordance with standards of procedure established in our unit and described previously15.All CMR images were acquired using a 1.5 T  MRI scanners with a 5-channel cardiac surface coil in a supine position. All study participants were scanned using identical comprehensive imaging protocol. The study protocol included initial scouts to determine cardiac imaging planes. Cine images were acquired using ECG-gated bSSFP sequence with multiple breath-holds at end-expiration in three left ventricular (LV) long-axis (two-chamber (2Ch), three-chamber (3Ch) and four-chamber (4Ch)) planes. The ventricular two-chamber and four-chamber planes were used to plan a stack of short-axis slices covering the entire LV. The following imaging parameters were used: for 1.5 T scanner: repetition time (TR) = 3.3 ms, echo time (TE) = 1.6 ms, flip angle = 60°, voxel size = 1.8 × 1.7 × 8.0 mm16. Strain analysis included 2Ch, 3Ch and 4Ch cine images, and respectively, 3 preselected slices from the LV short-axis stack to correspond to basal, mid-ventricular and apical levels. The endocardial and epicardial contours drawn on cine images with QMass version 8.1 were transferred to QStrain RE version 2.0, where, after the application of tissue tracking algorithm, endocardial and epicardial borders were detected throughout all the cardiac cycle. These long-axis cine images were further used to compute global myocardial longitudinal (GLS) , however our findings, in agreement with previous studies18, show a lower reproducibility and less sensitivity to detect differences in myocardial deformation between groups, suggesting further its reduced potential role in clinical practice.All images were analyzed offline using commercially available software  in accordance to recent consensus document for quantification of LV function using CMRLS) Fig.  and, resLS) Fig.  strain a19. Atrial surfaces were derived from the CMR cine sequences corresponding to the maximal expansion of the atrial chambers following the current guidelines20. For quantitative analysis all the volumes, areas and mass were indexed with BSA.LV Volumetry and mass were derived from segmentation of endocardial and epicardail contours in end-diastole and end-systole phases respectively, following the current guidelines recommendationsStatistical analysis was carried out with SPSS IBM statistics, version 25. Normality of variables was assessed by visual assessment of normality curves and the Shapiro-Wilk test. Intra-subject comparison between strain values at 3 different levels Endo-, Myo-, Epi- were performed using 1-way repeated measures ANOVA and respectively Tukey’s multiple comparison tests. Comparison between groups for continuous variables was performed with a 2-sided, independent-samples Student’s t test or 1-way ANOVA for normally distributed data and Mann-Whitney and Kruskal-Wallis tests for skewed data. When a significant p value was obtained using 1-way ANOVA, the group means were examined by unpaired t tests for normally distributed variables or log-transformed values , followed by Bonferroni post-hoc correction. ROC analysis with determination of specific area under curve (AUC) and threshold Youden’s index to establish optimal predictive power were computed. Results are presented as mean ± SD. Values of p < 0.05 were considered statistically significant.A total number of 140 patients with a diagnosis of HF were screened for the inclusion criteria, as stated above, and a resultant number of 59 patients were finally recruited for the study, as follows: 18 were diagnosed with HFpEF, 21 with HFmrEF and 20 with HFrEF. Patients with AF, haemodynamically significant valvulopathies, uncontrolled hypertension, generic contraindications for CMR such as implantable devices, severe renal insufficiency, claustrophobia, were excluded. There were no differences between the control group and HFpEF for LV end-diastolic or end-systolic volumes or ejection fraction, as expected LV end-diastolic volume was progressively larger in patients with HFmrEF and HFrEF respectively. Patients with HFmrEF and HFrEF had a more dilated ventricle and left atrium. LV wall thickness was slightly larger in all 3 HF groups compared with normal measured at septum level there was no difference in the free wall, LV mass was higher in HFmrEF and HFrEF groups but there was no difference between HFpEF and Normal. Incidence of relevant comorbidities demonstrated a uniform distribution between the pathology groups . GLS was able to discriminate between Normal and HFpEF groups  Fig. . In contSimilarly GCS and GCSR intrasubject paired comparisons between Endo-, Myo- and Epi- layers of the myocardium showed a progressive decrease  and epicardium .This gradient is blunted in patients with more severely impaired EF suggesting the primary and proportionally more important loss of physiological contractile properties of the subendocardial myocardium.GCS is not different between HFpEF patients and normal controls in any of the myocardial layers and our data suggests that this parameter cannot be used to detect contractile impairment in these patients.GLS is on average significantly lower in HFpEF compared with Normal but this parameter is not specific and, in our cohort, almost half of the HFpEF patients had normal GLS. Corollary, our study proposes that a GLS threshold could be used to identifiy in the HFpEF group a subgroup of patients with putative significant underlying systolic impairment.Endo- GCS shows the best ability to diagnose patients with systolic HF and, in tandem with Endo- GLS, to identify with maximal sensitivity patients with systolic HF from our cohort.Our study findings can be summarized as follows:et al.21 who used comparatively speckle tracking and strain-encoded magnetic resonance imaging methodology to detect segmental hypokinesia.Firstly, we report an important difference of magnitude for both GLS and GCS values depending of the level at which these parameters are assessed. In both cases, there is a significant endo-epi gradient with the highest values found towards the endocardium and the lowest towards the epicardium. Our findings support the hypothesis that subendocardial fibers play a privileged role in maintaining a physiological contractile power with a greater quantitative contribution, compared with fibers with myocardial and epicardial distribution. Proportionally, the strain values measured at an endocardial level dropped more with the severity of heart failure and myocardial remodeling. In keeping with this paradigm, we showed that measuring GCS at an endocardial level offers the best parameter to discriminate patients with systolic impairment, even if milder, such as HFmrEF group, from a normal population. These findings were in line with previous results of Altiok 25, coronary artery disease26, aortic stenosis27, hypertrophic cardiomyopathy29. There is a consensus among these studies regarding the existence of a marked gradient between subendocardial and subepicardial regions of the myocardium in normal subjects which decreases proportionally with the contractile impairment: in coronary artery disease (CAD) patients this gradient decreases with the severity of coronary obstruction26, in hypertension it is only mildly blunted compared with hypertrophic cardiomyopathy28.Several echocardiography studies assessed myocardial strain using a multilayer approach in normal subjects31. Histologically, circumferential fibers outnumber those with longitudinal and transversal orientation, especially at the base of the ventricle, with a ratio of 10:132. Using a mathematical modeling of the LV, Stokke et al.33 argued that GCS is accountable for generating two times more contractile force than GLS and with a steeper positive correlation with the EF. Our data indicate higher absolute values of circumferential than longitudinal strain and a more severe decrease of GCS from normal towards patients with systolic heart failure (HFmrEF and HFrEF), pari passu with the decrease in EF.The relative contribution of GCS and GLS to pump function of the heart, in normal and pathologic conditions, is controversial34. Recent ESC guidelines14 identifies HFmrEF as a potentially different pathologic entity from the more typical HFrEF group. HFmrEF class comprises patients with symptoms but not signs of HF, an intermediate degree of systolic dysfunction (EF between 40 and 50%) and with other traits of the disease present such as elevated natriuretic peptides, diastolic dysfunction, enlarged left atrium. Initial echocardiography studies in HFmrEF show mixed traits shared by both HFrEF and HFpEF such as the combination of LV dilatation with depressed contraction and respectively, increased stiffness and elevated diastolic filling pressures. Describing only discrete differences and similar patterns in strain values and interlayer gradients between HFmrEF and HFrEF, our study suggests that HFmrEF follows a similar pathophysiological pathway with HFrEF and likely represent a more incipient stage.Based on a segmental approach we propose generic threshold values for both GCS and GLS to identify patients with contractile impairment. We showed further excellent sensitivity of these combined values to identify patients with HF and, moreover, to scale the severity of disease, efficiently separating HFmrEF from HFrEF. While EF is a robust prognostic factor in a large number of patients with frank HF, with severely depressed cardiac contraction, its role per se in borderline subnormal and mid-range EF patients seems to be more controversial35. Importantly, in our study, GCS in HFpEF group was not different from normal. In agreement with previous echocardiography studies37, we found that GLS is on average decreased in the HFpEF group compared with controls, however, due to a wider variation, its specificity to discriminate HFpEF patients from controls is low  even if representative for a specific disease class, the groups of patients were small and more comprehensive studies are warranted to validate our findings in a widespread HF population, (2) in most of our patients the etiology of heart failure is mostly related to coronary artery disease and previous acute coronary events, an extrapolation of our findings to a more complex group of HF patients, especially those affected by an intrinsic cardiomyopathy, is warranted, (3) myocardial deformation can vary significantly between individual regions of the heart even in the absence of structural alterationsMultilayer evaluation of cardiac contraction is a convenient and fast procedure that can be obtained from basic CMR cine images. Measurement of strain and strain rate must be done cautiously as their range varies amply within the myocardial volume. Sub-endocardial regions and respectively circumferential strain seems to offer the best discriminative tool for the identification of patients with HF.Supplementary Information


Hibernation is an important and reversible cause of myocardial dysfunction in ischaemic heart failure.Hibernation is an adaptive process that promotes myocyte survival over maintaining contractile function. It is innate to mammalian physiology, sharing features with physiological hibernation in other species. Advanced imaging methods have reasonable accuracy in identifying hibernating myocardium. Novel superior hybrid methods may provide diagnostic potential. New evidence supports the role of surgical revascularisation in ischaemic heart failure, but the role of viability tests in planning such procedures remains unclear. Research to date has exclusively involved patients with ambulatory heart failure: Investigating the role of hibernation in ADHF is a key avenue for the future.Whilst our understanding of hibernation pathophysiology has improved dramatically, the clinical utility of identifying and targeting hibernation remains unclear. Despite, and in part due to improving revascularisation techniques, ischaemic heart disease (IHD) remains the most prevalent cause of chronic heart failure in developed nations . Even wiStudies across a range of modalities have demonstrated that most patients with ischaemic heart failure have a reduced left ventricular ejection fraction (HFrEF). Transmural infarction accounts for a significant proportion of this myocardial dysfunction. There was early recognition, however, that function is commonly impaired in myocardial segments that are free from ischaemic scar and have preserved metabolic activity, and also that a proportion of patients with coronary disease and HFrEF have no clinical or imaging evidence of prior infarction. Subsequent observations by Brundage and others suggested that contractile function in these regions commonly, but not inevitably, improved following revascularisation with coronary artery bypass grafting .These observations led to Shahbudin Rahimtoola’s first description of myocardial hibernation . This thEarly nuclear cardiology studies established that the degree of myocardial dysfunction in hibernation correlates with the extent of inducible perfusion defects . HibernaIn considering this theory, it is important to separate ischaemia  from hypoperfusion . Across the spectrum of normal physiological function, there is precise matching of coronary perfusion to myocardial oxygen demand, a relationship that is maintained in many pathological states but has been questioned in hibernation. Early animal work demonstrated biochemical ischaemia to be absent at rest, but controversy has remained with regard to perfusion. The ongoing controversy has centred on whether hibernating myocardium is constantly hypoperfused (and therefore supply and demand remain coupled) or whether hypoperfusion and ischaemia only occur in the context of increased physiological requirement (with supply and demand uncoupled and demand downregulated below the available supply at rest), e.g. on exertion.Recent investigations in a well-validated swine model have shown that repeated ischaemia with normal perfusion in between episodes is sufficient to induce hibernation . The sevEarly histopathological studies utilising ventricular biopsies taken at bypass surgery demonstrated consistent morphologic changes, characterised by myocyte de-differentiation (as opposed to degeneration) and varying degrees of loss of contractile apparatus  . These cRecent years have seen further progress in our understanding of the pathophysiology of hibernation. Research in swine has demonstrated the reversibility of histological changes and myocyte proliferation associated with functional recovery following revascularisation •. CleareMoving to the clinical aspects, the first challenge in managing hibernation is to accurately identify it. The definition of hibernation is retrospective: the observation of functional recovery following revascularisation. Contemporary tests attempt to prospectively predict this recovery, with variable success. The term “viability” is commonly used to prospectively classify of all dysfunctional but non-infarcted myocardium. The term is often, but incorrectly, used interchangeably with hibernation: whilst hibernation represents a substantial proportion of the dysfunction observed in patients with ischaemic heart failure, other pathophysiological processes may result in similar reductions of contractile function in non- infarcted segments. These include cardiomyopathy, acute ischaemia, transient myocardial stunning, adverse remodelling, and partial thickness infarction. As with hibernation, these states may co-exist within the ventricle or a single myocardial segment.Early phenotyping refers to the use of cardiac biomarkers, imaging tests and physiological assessment to identify aetiology at the time of initial presentation with heart failure. The supposition is that by understanding the pathological mechanisms at work in any given patient, treatment can be personalised and tailored to improve outcome. Phenotyping ischaemic HFrEF is challenging: initially one must identify coronary disease, then subsequently determine causality (is this ischaemic heart failure or non-ischaemic heart failure with “bystander” coronary disease?) and subsequently sub-classify the pathological state of each region of myocardium to potentially guide therapy. It is the last aspect that is most relevant to hibernation. International guidelines support the use of imaging to identify the presence of IHD in acute heart failure  but the Of the imaging modalities available for phenotyping ischaemic heart failure, the most marked recent developments have been in cardiac MRI. IHD can be identified either through the demonstration of ischaemic patterns of myocardial scar or the presence of inducible perfusion defects using vasodilator stress testing. Acute infarction can be identified through areas of myocardial oedema, an assessment not available in any other imaging modality. Quantification of late gadolinium enhancement (LGE) provides useful prognostic information in patients with- and without- left ventricular dysfunction .The extent of ischaemic-pattern left ventricular myocardial infarction determined by LGE-CMR has an excellent specificity for the diagnosis of ischaemic heart disease. The simultaneous acquisition of reference-standard data on ventricular systolic function further increases clinical and prognostic utility. Not all patients with ischaemic HFrEF, however, will have imaging evidence of prior infarction. This raises a concern if LGE-CMR is used in isolation: the sensitivity of LGE-CMR alone for an ischaemic aetiology may be reduced, in particular in patients with a greater volume of reversible hibernation, assuming matched levels of dysfunction. This could lead to missed opportunities if an incorrect diagnosis of dilated cardiomyopathy is made. The present role of CMR is, therefore, sub-classifying myocardial pathology and planning revascularisation once the diagnosis of ischaemic heart failure has been made.As discussed above, cardiac MRI is unable to prospectively identify hibernation per se. Given, however, that hibernation accounts for the majority of dysfunctional but non-infarcted myocardium; its presence is (imperfectly) inferred from the absence of scar. The initial demonstration of MRI viability assessment using LGE was in 2000 , and sinEchocardiography is less expensive and more widely available than CMR and is central to establishing the diagnosis of HFrEF. Features such as regional wall motion abnormalities, variation in wall thickness and ischaemic mitral regurgitation can point towards an ischaemic aetiology. Resting echocardiography has some utility at ruling in or ruling out viable myocardium at the extremes of the spectrum of segmental dysfunction. Preserved end diastolic wall thickness (EDWT) > 8 mm shows reasonable diagnostic accuracy for hibernation , whilst values < 6 mm nearly, excludes recovery  . The preStress echocardiography (DSE) remains the most widely available test of myocardial viability. Investigations of DSE have focussed on the minimum number of viable segments needed to predict a significant improvement in global LV function following  revascularisation. These have shown that demonstrating 4–6 viable segments has the best diagnostic performance, with a lower sensitivity but higher specificity than CMR . A biphasic myocardial response, where contractility improves at low dose then deteriorates with increasing stimulation appears to have the greatest diagnostic accuracy ; the preCardiac catheterisation in the form of invasive coronary angiography is a frequently used diagnostic test in suspected hibernation, particularly in decompensated patients in whom a coexisting acute coronary syndrome is considered. Angiography permits detailed assessment of the coronary vasculature, as well as the acquisition of other useful prognostic data, such as left ventricular end diastolic pressure (LVEDP). Procedural duration and the deleterious effects of atrial fibrillation on diagnostic accuracy are significantly reduced compared with other modalities. Avoiding pharmacological stress may benefit patients who are acutely haemodynamically compromised. Contrast nephropathy remains a risk, given the frequency of acute or chronic renal impairment.Whilst ideal for detecting coronary disease, used in isolation invasive angiography cannot determine causality. As discussed above, the extent of angiographic disease or myocardial jeopardy required to induce hibernation has not been determined, though a continuous relationship between coronary disease burden and likelihood of an ischaemic aetiology can be hypothesised. Angiographic stenosis severity also correlates poorly with objective perfusion assessments, a factor likely to be as important in ischaemic heart failure as it is in chronic stable angina . FinallyDetailed physiological tests, such as fractional flow reserve (FFR) or instantaneous wave-free ration (iFR) might provide relevant data on physiological stenosis severity. These tests have not been validated in HFrEF; however, the diagnostic thresholds required to induce hibernation are likely to be substantially lower than those used to predict ischaemia in those with normal ventricular function . Novel physiological markers, such as the index of microcirculatory resistance (IMR) and wave intensity analysis (WIA) offer the opportunity to simultaneously assess myocardial physiology, but at present are restricted to research environments •, 40. VeNovel imaging modalities under development may permit more accurate characterisation of hibernating myocardium. It is notable that, with the exception of high-dose DSE, each of the testing modalities currently available assesses a single aspect of the physiology of hibernation. Advanced intracoronary physiology, hybrid PET/MRI, PET/CT and stress/LGE-CMR all benefit from facilitating simultaneous assessment of multiple facets of hibernation physiology. The integration and co-registration of metabolic, perfusion, ischaemia and morphologic imaging with the distribution of the coronary vasculature could well unlock the accurate prospective identification of hibernating myocardium.The role of revascularisation in ischaemic HFrEF has long been contentious, even without consideration of hibernation. After many years and conflicting data on the role of coronary artery bypass grafting (CABG) in ischaemic HFrEF, 10-year follow-up of the STICH trial recently confirmed a statistically significant benefit in cardiovascular mortality for CABG plus medical therapy over medical therapy alone ••. This Whilst percutaneous coronary intervention (PCI) is the most frequently used treatment for an acute coronary syndrome, there has been no prospective randomised investigation of the utility of angioplasty in the management of stable ischaemic HFrEF. Observational data demonstrates that treatment with PCI can result in comparable improvements in ventricular function, with some evidence that revascularisation of chronic total occlusions (CTO) provides particular benefit •. There The REVIVED-BCIS2 trial is a multicentre UK study led by our group and will be the first randomised evaluation of the impact of revascularisation via PCI on mortality, morbidity and left ventricular function in patients with severe ischaemic HFrEF . With 40Whilst emerging evidence supports the role of revascularisation in ischaemic HFrEF, specific data for the role of hibernation/viability testing in determining revascularisation outcomes remain limited. There is clear evidence of greater improvements in function with an increasing burden of hibernation . The ideAlthough often used as a surrogate endpoint, there is sparse data linking viability testing and myocardial functional recovery to improvements in hard outcomes , with conflicting results , 51. ThiSoon after the initial case reports, associations were made between the provision of revascularisation in those with significant viable myocardium and improved mortality in ischaemic heart failure. Allman and colleagues  meta-anaThere were several subsequent attempts to address the question of viability in guiding revascularisation, which struggled with low recruitment despite the best efforts of the investigators , 56. TheIn contrast to the STICH trial, recruitment to the REVIVED-BCIS2 trial is dependent on presence of a significant degree of presumed myocardial hibernation . The eligibility requirements will also make this the first adequately powered prospective study of viability-guided management. Pre-planned sub-analyses of the data will investigate the role of hibernation in determining outcomes in both the revascularised and medically managed arms of the trial.Whilst hibernating myocardium may remain stable over months , the preWhilst not specifically investigated, identifying hibernation in ADHF is likely to be more challenging. Whilst resting transthoracic echocardiography remains the mainstay of diagnosing LVSD, dobutamine-stress testing is inadvisable in decompensated heart failure. Coronary angiography remains the diagnostic investigation of choice, particularly in patients where acute coronary syndromes cannot be excluded on clinical grounds alone.CMR has received considerable attention for phenotyping in acutely presenting cardiology patients, and there is no major reason to believe LGE-CMR assessment would be invalidated by decompensation. That said, dysfunction due to adverse loading conditions may mimic hibernation, potentially leading to reduced specificity. Vasodilator stress perfusion may also be affected by the adverse loading conditions and venous pressure in decompensated heart failure, factors which have not been specifically investigated. The MRI environment and long-scan time may also be unsuitable for unstable patients. Differentiating myocardial oedema and established scar is challenging, particularly relevant to patients presenting with ischaemic ADHF, where determining whether an acute coronary event has occurred is often challenging and confounded by a prior history of IHD and modest elevations in cardiac biomarkers. Despite the majority of patients presenting without clinical evidence of ACS, troponin elevation is near ubiquitous in patients hospitalised with ischaemic ADHF, being observed in 85% of patients .Such troponin elevations have recently been shown to be highly correlated with the extent of hibernation but not with established scar, suggesting subacute injury in hibernating myocardium as the mechanism of troponin release •. The usObservational evidence for the role of acute revascularisation in decompensated HFrEF is extremely limited, in part because it is rarely utilised in current clinical practice. Angiography remains underutilised in the acute setting, with recent data from the BIOSTAT-CHF programme demonstrating that only 12.5% of patients underwent angiography within 30 days of decompensation •. Of 170The last decade has seen significant advances in our understanding of hibernation and its role in ischaemic left ventricular dysfunction. In particular, progress has been made in pathophysiological research, relevant diagnostics (particularly coronary physiology and CMR) and revascularisation techniques . These have contributed to far greater understanding of the role of revascularisation in ischaemic heart failure. Our knowledge of the utility of these techniques in the setting of decompensated heart failure remains primitive and is an essential avenue for future investigation.


Congestive heart failure is rarely observed in patients with acromegaly. Excessive growth hormone secretion and elevation of insulin-like growth factor 1 contribute to pathological changes in myocyte growth and structure, cardiac contractility, vascular function, and in later stage may progress to cardiac dysfunction. Early recognition of the condition is paramount, though the insidious progression of the disease commonly results in late diagnosis. Current standard regimens of pharmacological therapy, surgical treatment, radiotherapy are designed to normalize serum levels of both insulin-like growth factor 1 and growth hormone. In patients with late-stage heart failure due to acromegalic cardiomyopathy, cardiac resynchronization therapy might be a desirable treatment to help cardiac synchronization, improve symptoms, and eventually reduce hospital admissions together with mortality rates.We describe a case of a 49-year-old man with a history of acromegaly who presented to our hospital with a diagnosis of decompensated systolic heart failure. Serial electrocardiograms showed wide (160–200 ms) QRS duration with left bundle branch block. Echocardiography showed severe left ventricular dysfunction that simultaneously achieved a left ventricular ejection fraction of 16%. Surgical indication was rarely assessed by neurosurgeons. Given that the stereotactic radiosurgery together with pharmacotherapy produced infinitesimal effects, cardiac resynchronization therapy was performed. Owing to biventricular synchronization and holding back reverse remodeling, the patient’s symptoms were successfully alleviated, and he was discharged from the hospital.Congestive heart failure is a rare complication in acromegaly-induced cardiomyopathy (occurs in only 3% of patients). Early diagnosis and treatment with curative drugs more than cardiovascular implantable electronic devices might lead to better surgical outcomes in this group of patients. Acromegaly presents with multisystem involvement, and cardiac manifestations remain an important cause of mortality , 2. ChroWe report a case of a patient with acromegaly who was diagnosed with severe cardiac failure at the time of diagnosis and failed to recover cardiac function after pharmacotherapy and radiotherapy. Though successful resection of the pituitary adenoma was crucial, low left ventricular ejection fraction (LVEF) value in alignment with poor cardiac function could have made the surgery life-threatening. We applied mechanical therapy as CRT to this patient, which helped better control acromegalic cardiomyopathy, and this approach may create further chances for subsequent surgical resection.2. His blood pressure was 110/60 mmHg, and his heart rate was 92 beats/min with sinus rhythm. He had distinct skeletal features that included prominent superciliary arches and nose bridge, enlargement of the tongue and lip, and large hands and feet. Cardiac auscultation revealed irregular premature beats and pathological third heart sound, and a systolic murmur was discovered over the apex and aortic area. Bilateral extensive borders of cardiac dullness were noted. His physiological reflexes were present without any pathology. An electrocardiogram demonstrated sinus rhythm with wide (160 ms) QRS duration of left bundle branch block (LBBB)  at the time of diagnosis 20 years before. The patient was overweight and moderately nourished. He was 1.85 m (73 inches) tall, weighed 134 kg, and had a body mass index of 39 kg/mOn admission, magnetic resonance imaging showed pituitary macroadenoma. Given the symptoms described, we arranged blood testing of myocardial injury markers showing an elevated brain natriuretic peptide level of 740 pg/ml indicating cardiac failure Table . HormoneA Holter monitor was ordered for underlying arrhythmias to explain the patient’s dyspnea, chest discomfort, and presyncope. It demonstrated sinus rhythm with an average heart rate of 68 beats/min, frequent ventricular premature beats, and nonsustained ventricular tachycardia up to 2200 ms)  of 78%. Echocardiography showed diffuse impairment of left ventricular (LV) systolic motion, reaching an LVEF of 16%. We noted hypertrophy of the ventricular septum at 18 mm, ventricular dilation, with LV diameter of 72 mm. The right ventricle and atrium and the left atrium were also dilated with moderate mitral regurgitation and mild tricuspid regurgitation. There was no associated systolic anterior motion (SAM) of the mitral valve. Dyssynchrony of the biventricular systolic motion was apparent.Given an exertional component to the symptoms together with echo presentations in order to better exclude ischemic cardiomyopathy, coronary angiography was performed, which showed normal coronary arteries without stenosis, and left ventriculography applied simultaneously revealed an EF of 20% with diffuse LV hypokinesis.Given the patient’s previous medical history of acromegaly, the absence of obstructive coronary artery imaging findings or segmental dyskinesia, family history of hypertrophic cardiomyopathy (HCM), symmetric hypertrophy, as well as absence of SAM of the mitral valve, acromegaly-induced cardiomyopathy was confirmed, which was absolutely opposed to coronary heart disease (CHD) and HCM.These results indicated that it was probably not a case of hereditary cardiomyopathy; therefore, we diagnosed the patient as having secondary dilated cardiomyopathy due to acromegaly, even taking it a step further progressing to congestive heart failure secondary to acromegaly-induced dilated cardiomyopathy.Chronic excess of GH and IGF-I secretion affects cardiac morphology and performance , so etioTelephone follow-up was arranged, and the patient claimed symptom improvement following the device insertion 1 month later and was basically back to normal life. We required that he return for follow-up at 1 month, 3 months, and 6 months after the interventional therapy. The patient has been followed in our outpatient clinic for nearly half a year now. During his last visit, echocardiography identified improved LVEF of 54%, and a chest x-ray showed reduced CTR of 60%. The patient was in NYHA functional class II  and attributed to acromegaly-induced dilated cardiomyopathy. He eventually had a dramatic response to medical device therapy. This case reinforces the importance of careful examination, accurate diagnosis, detailed evaluation, and searching for better alternative treatments when standard therapy initially fails.Acromegaly is a rare endocrine disorder with an incidence of 3 per 1 million per year , 4, 6. GCurrent treatments aim to normalize GH and IGF-1 secretion levels in patients with acromegaly for the sake of reversing some of the morphological changes in the early stage, regression of cardiac hypertrophy and improvement of cardiac dysfunction , 18–20. CRT is an effective and well-established therapy for patients with heart failure, LV systolic dysfunction (LVEF ≤35%), and electrical dyssynchrony, demonstrated by a surface QRS duration of ≥ 130 ms . It appe