Tricuspid regurgitation after left-sided valve surgery was a common and difficult problem. Atrial fibrillation was considered to be an important etiology of tricuspid regurgitation. His-Purkinje system pacing (HPSP) was a physiological pacing method, which could prevent and treat heart failure and might reduce tricuspid regurgitation. Our study aimed to investigate the effect of HPSP on tricuspid regurgitation in patients with persistent atrial fibrillation after left-sided valve surgery.This study was a retrospective study. The 3-year patient review focused on those who underwent permanent cardiac pacemaker implantation of HPSP after mitral valve and/or aortic valve replacement from Jan 1st, 2019 to Jan 1st, 2022. HPSP included His bundle pacing (HBP) or left bundle branch pacing (LBBP). Clinical data collected included electrocardiogram, pacing parameters, ultrasonic cardiogram parameters and chest x-ray at implantation and 3-month follow up. Univariate and multivariate linear regression analysis of tricuspid regurgitation velocity were performed.P = 0.007). The tricuspid regurgitation velocity significantly decreased  and tricuspid valve pressure gradient (PG) reduced . The cardiothoracic ratio of patients was significantly lower than that before implantation . The NYHA classification of patients also improved (P = 0.013). In multivariate liner regression analysis, the pacing ratio  was an independent determinant of tricuspid regurgitation velocity variation.A total of 44 patients was retrospectively reviewed. Eight patients who had undergone implantation of HPSP after left-sided heart valve replacement were enrolled in the study. All patients had persistent atrial fibrillation. Three of them received HBP and five underwent LBBP. At 3-month follow-up, the tricuspid regurgitation grade was significantly lower than that before implantation (HPSP might reduce tricuspid regurgitation and improve cardiac function in patients with persistent atrial fibrillation after left-sided valve surgery. Left-sided valve surgery was a common procedure for left heart valve  disease. About 69,000 patients in China underwent valve replacement or repair operations every year . SecondaMore than 90% of the patients after left-sided valve surgery had persistent atrial fibrillation (AF) , which cTherefore, we retrospectively reviewed patients with tricuspid regurgitation after left-sided valve surgery who underwent HPSP to assess the effect of HPSP on tricuspid regurgitation and heart function.This study was a retrospective study. Patients who underwent permanent cardiac pacemaker implantation of HPSP at Peking University International Hospital from January 1st 2019 to January 1st 2022 were consecutively enrolled. Inclusion criteria: (1) with successful implantation of HPSP; (2) after left-sided heart valve  replacement; (3) with complete baseline and follow-up data.β blockers, spirolactone, loop diuretics and statins; (4) Baseline clinical data at hospitalization before pace maker implantation, including heart function classification of New York Heart Association (NYHA), mean heart rate (HR) from the Holter, systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin, serum creatinine and brain natriuretic peptide (BNP); (5) Electrocardiogram (ECG) characteristics including QRS duration (QRSd); (6) Last preoperative ultrasonic cardiogram (UCG) parameters included left atrial anteroposterior diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), right atrial left-right diameter (RAD), Right ventricular left-right diameter (RVD), mitral valve regurgitation (MVR) grade, tricuspid valve regurgitation (TVR) grade and velocity, pressure gradient (PG), pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE), right ventricle fractional area change (RV-FAC) and inferior vena cava diameter (IVCD); Estimation of PASP: PASP = 4*(peak velocity of tricuspid regurgitation)2 + right atrial pressure; (7) Cardiothoracic ratio from last preoperative chest x-ray.Clinical data of patients were collected through an electronic medical record system. The baseline data included: (1) Basic information including age, gender, valvular disease history, valve surgery history, AF history, pacing indication, current smoker and drinker; (2) Comorbidity including hypertension, diabetes mellitus, coronary disease, stroke and chronic kidney diseases (CKD); (3) Medications for long-term use which may influence heart function including angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), The research was compliance with the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Peking University International Hospital.A C315 delivery sheath  and 3830 electrodes  were used to place the pacing electrodes of the His-Purkinje system. Under the guidance of x-ray, in the right anterior oblique position of 30° (RAO 30°), the tip of the wire was mapped to find the His potential near the tricuspid annulus. When the His potential was mapped, we rotated and fixed the lead, and then measured the pacing parameters. If the His bundle was captured and the threshold was <2.0 V/0.4 ms, the His bundle lead was retained; otherwise, LBBP was performed .Referring to the 9-partition method of the left bundle branch, the LBBP lead was located at or near the basal lower one-third junction of the ventricular fluoroscopic image in the RAO 30° position . We threThe right ventricular low-septal pacing electrodes  were placed as backup in all patients. The electrodes were connected to the pacemaker . The capture threshold, sensing amplitude, and pacing impedance were recorded. Threshold values were considered with a pulse width of 0.4 ms for all patients. The lower rate for HPSP was set at 60 bpm.All patients stopped taking medications that lowered their heart rate to determine the pacemaker indication and received adequate and optimized drug therapy before implantation. After implantation, patients with tachycardia took drugs to control the ventricular rate to ensure high pacing ratio. Other long-term medications were also reinstated.The patients were followed up by regular clinic visits after implantation, and related data were recorded at the same time. All the patients underwent electrocardiogram, chest x-ray and echocardiography at 3 months after implantation. QRS duration and cardiothoracic ratio were recorded. Echocardiographic parameters same as baseline data were included. Pacing parameters were measured by programming control.P < 0.05 was considered to indicate statistical significance. The SPSS 23 software  was used.Continuous variables conforming to normal distribution were presented as mean ± SD (standard deviation). Skewed variables were presented as median (interquartile range [IQR]). Discrete variables were presented as frequencies (n) and percentages (%). To compare groups, paired student's t-test was used for normally distributed continuous variables while Mann-Whitney U tests for skewed continuous variables and ordered categorical variables. Linear regression was performed to identify the independent determinants of TVR velocity. All statistical tests were two-tailed. n = 35). One patient who had no follow-up data was excluded. Finally, a total of 8 patients were enrolled in the study, with an average age of 74. Six of the patients were male, and six had rheumatic heart disease. Five patients underwent mitral valve replacement (MVR), two patients underwent aortic valve replacement (AVR), and one patient underwent combined valve replacement. The average postoperative time was 7.8 years. All patients had persistent atrial fibrillation. The average time of onset of AF was 12 years. Three patients underwent pacemaker implantation for symptomatic bradycardia, three for long intermittent and two for complete AVB. Most patients had other chronic diseases such as hypertension, coronary disease, diabetes mellitus, stroke and CKD. All medications which may affect heart function were recorded. The mean heart rate of the patients before implantation was 58.3 ± 12.1 bpm. Baseline characteristics of the patient population are listed in . But all the QRS were still narrow and the duration was less than 120 ms. The QRS duration of LBBP was 92 ± 13 ms at baseline and increased to 102 ± 10 ms after implantation (P = 0.040), while the QRS duration of HBP had no change.Of the 8 patients, 3 received HBP, and 5 received LBBP. The QRS duration of post-implantation was longer than that of pre-implantation . The impedance and threshold of LBBP at 3-month follow-up were significantly lower than those at implantation , and the sensing amplitude remained stable. The mean heart rate of the patients at 3-month follow-up was 68.1 ± 6.9bpm, which was higher than before implantation (P = 0.027). The pacing ratio of the patients was 45.2%-94.0%. Detailed data was listed in the . The tricuspid regurgitation velocity significantly decreased  and tricuspid valve pressure gradient (PG) reduced . The estimated PASP was also significantly lower after implantation . LAD was reduced to some extent, but the difference was not statistically significant (P = 0.089). The diameter of other atria and ventricles, TAPSE, RV-FAC, IVCD did not change significantly compared with that before pacing . They suffered from moderate to severe tricuspid regurgitation and had no or mild mitral regurgitation. TAPSE and RV-FAC were in the normal range in these patients. At the 3-month follow-up, the tricuspid regurgitation grade of the patients was significantly lower than that before pacemaker implantation (P = 0.017) (P = 0.013). Six patients had class 2 of NYHA, one had class 1 and one had class 3  . The act class 3 .P < 0.2 in the univariate regression analysis  and factors commonly considered to be associated with tricuspid regurgitation and heart failure  were included in the multivariate linear stepwise regression analysis  was the only independent determinant of tricuspid regurgitation velocity variation.There were many factors affecting tricuspid regurgitation. A univariate regression for the variation of tricuspid regurgitation velocity variation was performed to identify the influencing factors . The varanalysis . We founCase 6 was a 65-year-old male, who was admitted to the hospital because of rheumatic valvular heart disease and heart failure. His chief complaint was shortness of breath after exercise and edema of lower extremity for more than 30 years, which was aggravating for one month. The patient underwent mechanical mitral valve replacement 6 years ago. After adequate diuretic treatment, the patient's symptoms were not completely resolved. The echocardiography showed that the mechanical mitral valve worked well and LVEF was 69%. But he had severe tricuspid regurgitation and his regurgitation velocity was 476 cm/s . The eleIn our study, we found that HPSP reduced tricuspid regurgitation grade, velocity and PG in patients with persistent atrial fibrillation after left-sided valve replacement and improved heart function. The pacing ratio of HPSP was independently associated with tricuspid regurgitation velocity, which indicated heart rate control and rhythm regularization of atrial fibrillation may be principal reason for the effect.The mechanism of tricuspid regurgitation after left heart valve surgery was unclear. Severe left heart valve disease caused elevated left atrial pressure and pulmonary hypertension, leading to right heart insufficiency, tricuspid annular dilatation, and subsequent tricuspid regurgitation. However, the above-mentioned mechanism could not explain occurrence of tricuspid regurgitation after left heart valve surgery, because severe pulmonary hypertension and heart failure had significantly improved in most patients after successful valve surgery. Several years later, these patients gradually developed severe tricuspid regurgitation, while the left heart valve function remained normal, and there was no obvious left heart failure –5. As inThe treatment of valvular atrial fibrillation was difficult. Because of the fibrosis of the atrial matrix, radiofrequency ablation was ineffective and it was difficult to maintain sinus rhythm . SeveralThe traditional understanding was that the electrodes across the tricuspid valve mechanically prevented the valve from closing, which was the primary reason for tricuspid regurgitation of right ventricular pacing (RVP) . HoweverThere were some differences in pacing function between HBP and LBBP. HBP could achieve a physiological pacing and the paced ECG was close to normal. But there were problems such as difficult implantation, low sensing amplitude and high pacing threshold . The lefFirstly, the sample size of our study was relatively small, because there were rare patients with after left-side valve replacement combined with pacing indication. We consecutively enrolled all patients who received HPSP in our heart center in the last 3 years. The samples were assumed to be representative. And at 3 months follow-up, the tricuspid regurgitation grade, flow velocity and PG were all significantly reduced compared with those before pacing, which may be not by chance. Secondly, HPSP was not compared with traditional RVP in our study. Due to the popularity of physiological pacing in recent years, RVP was not routinely recommended for patients with atrial fibrillation complicated with heart failure or tricuspid regurgitation. From the results of the current studies, HPSP may be the better choice. Thirdly, we did not find the direct effect of HPSP on left and right heart function perhaps due to the short follow-up time. Future study could include a larger sample size and longer follow-up to explore the effect of HPSP on tricuspid regurgitation and heart function in patients with persistent atrial fibrillation after left-sided valve surgery.Our study found that HPSP might reduce tricuspid regurgitation and improve heart function for patients with persistent atrial fibrillation after left-sided valve surgery, which may be associated with heart rate control and rhythm regularization of atrial fibrillation. This may be a novel treatment option for patients with tricuspid regurgitation after left-sided valve surgery who were at high risk of reoperation.


Left ventricular GLS correlated significantly with T1  and LVEF . Left ventricular GLS less negative than −15% was 7.5 times more likely in patients with prolonged T1 . The reduced basal inferolateral longitudinal strain had a significant impact on the global left ventricular longitudinal strain. ROC results suggested that a GLS of 14.5% predicted prolonged T1 relaxation time with the best sensitivity and specificity. Conclusions: CMR abnormalities, including a myocarditis pattern, are common in patients who have recovered from COVID-19. The CMR feature-tracking left ventricular GLS is related to T1 relaxation time and may serve as a novel parameter to detect global and regional myocardial injury and dysfunction in patients with suspected myocardial involvement after recovery from COVID-19.COVID-19 infection is associated with myocarditis, and cardiovascular magnetic resonance (CMR) is the reference non-invasive imaging modality for myocardial tissue characterization. Quantitative CMR techniques, such as feature tracking (FT) and left ventricular global longitudinal strain (GLS) analysis, have been introduced as promising diagnostic tools to improve the diagnostic accuracy of suspected myocarditis. The aim of this study was to analyze the left ventricular global longitudinal strain (GLS) and the influence of T1 and T2 relaxation times, ECV, and LGE appearance on GLS parameters in a multiparametric imaging protocol in patients who recovered from COVID-19. The 86 consecutive patients enrolled in the study had all recovered from mild or moderate COVID-19 infections; none required hospitalization. Their persistent symptoms and suspected myocarditis led to cardiac magnetic resonance imaging within 3 months of the diagnosis of the SARS-CoV-2 infection. Results: Patients with GLS less negative than −15% had significantly lower LVEF  and were significantly more likely to have prolonged T1 (28.6% vs. 7.5%;  COVID-19-associated myocardial injury is common and may occur as a direct result of myocardial viral infection or indirectly as a result of systemic inflammation, endothelial dysfunction, or microvascular thrombosis ,3. When Wall motion assessment is paramount for the detection of contractile functional impairment. With good endocardial border delineation and high tissue contrast, CMR offers significant advantages in this regard. However, given subjectivity and operator dependence, the need for quantification seems self-explanatory. Quantitation of myocardial deformation provides a more sensitive and robust evaluation of both atrial and ventricular function and has recently been a fast-advancing field of CMR, allowing for the detection of subclinical myocardial disease in a variety of cardiovascular conditions. Recent clinical studies have shown that global longitudinal strain (GLS) is a better diagnostic tool than left ventricular ejection fraction (LVEF) for many cardiac abnormalities, especially for detecting mildly impaired left ventricular function, allowing for early diagnosis . These sTo our knowledge, few studies have attempted to evaluate the relationship between myocardial longitudinal strain and other MRI parameters, especially in patients who have recovered from COVID-19. The aim of the present study was to analyze FT-derived left ventricular global longitudinal strain (GLS) and the influence of T1 and T2 mapping, ECV, and LGE extent on GLS parameters in a multiparametric imaging protocol in patients after recovery from COVID-19.A total of 86 consecutive patients who met all inclusion criteria and had no exclusion criteria were enrolled in the study at the post-COVID-19 cardiology outpatient clinic. The study’s inclusion criteria were as follows: 1. SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) swab; 2. Absence of clinical symptoms of active COVID-19 pneumonia; 3. Persistent symptoms, including chest pain, arrhythmia, dyspnea, or fatigue, suggestive of cardiac involvement. Exclusion criteria were a history of cardiac disease  and general contraindications to contrast-enhanced CMR (including end-stage chronic kidney disease and severe claustrophobia). Patients with other known cardiac diseases were also excluded to minimize the effect of non-COVID-19-related diseases on CMR results. All subjects had recovered from COVID-19, and the course of the infection was mild or moderate; none of the patients required hospitalization. Due to persistent symptoms and suspected myocarditis, CMR was performed, with a median time between the scheduled CMR evaluation and the initial COVID-19 disease diagnosis of 10 (6–14) weeks.The study was designed and conducted in accordance with the Declaration of Helsinki, and its protocol was approved by the Independent Bioethics Committee for Scientific Research at the Medical University of Gdansk . Written informed consent was obtained from all study participants.Details of CMR acquisition and analysis have been described previously ,5. All pThe GLS of the left ventricle was measured using CMR feature tracking, which involves the detection of “patterns of features” or “irregularities” in the endocardial border that are tracked and followed in successive frames of routine CMR cine . QuantitDiffuse fibrosis was assessed by extracellular volume calculations. Edema was determined by the signal intensity (SI) ratio of the myocardium to the skeletal muscle SI on T2-weighted images. All analyses, including traditional CMR features, were performed by the same two physicians  using commercial software . In the case of discordant results, a consensus decision was reached with a third experienced CMR reader. In a second step, CMR-FT was performed independently, with the readers further blinded to all other CMR findings, including LGE and LVEF.t-test or Mann-Whitney U test, depending on the distribution type. Categorical data were compared using the chi-squared test and Fisher’s exact test. Correlations were assessed with the Pearson or Spearman correlation test, depending on the distribution of the variables. We searched for independent risk factors for a diagnosis of global strain less negative than −15% using univariate logistic regression and then analyzed variables with p < 0.10 using multivariate logistic regression. Receiver operating characteristic (ROC) analysis was used to evaluate the predictive value of global T1 for global strain less negative than −15% and to determine the best cutoff for global T1 using the Youden index (J) method. A p value less than 0.05 was considered statistically significant. Data were analyzed using SPSS software v. 21 .Continuous data are presented as the mean and standard deviation (SD). Categorical data were presented as a percentage of the total. The normal distribution was tested using the Kolmogorov-Smirnov test. Continuous data from two groups were compared using the Student’s Finally, 81 patients  were included in the study; 5 patients were excluded because the quality of their CMR images did not allow CMR feature tracking strain analysis due to artifacts. The baseline characteristics of the included patients are presented in The mean GLS was −16% ± (−3), mean T1 was 1005 ± 34 ms mean T2 was 47.7 ± 3.7 ms, and mean ECV was 27± 5. Prolonged T1 was noted in 12 (15%) patients, prolonged T2 in 21 (26%) patients, and higher ECV in 13 (16%) patients. LGE was present in 52 (64%) patients. Overall, 7 (8.5%) patients met the LLC criteria for active myocarditis. Representative examples of longitudinal strain curves and LGE images from a patient with acute myocarditis are shown in Patients with reduced left ventricular global longitudinal strain (GLS) had significantly lower LV ejection fraction, significantly more prolonged T1, and significantly more positive late gadolinium enhancement .p = 073), r = −0.059 (p = 0.60), and r = −0.026 (p = 0.82), respectively. Left ventricular global longitudinal strain correlates positively and significantly with T1 and negatively and significantly with LVEF . There wMultivariate logistic regression analysis revealed that, among the selected variables, prolonged T1 was a significant independent predictive factor for an abnormal GLS less negative than −15%  .Univariate and then multivariate logistic regression were performed on CMR parameters, including segmental longitudinal strain and the continuous variables T1, T2, and ECV, for each of the 16 LV segments to evaluate the effect on reducing global LV longitudinal strain (GLS). Both longitudinal strain and T1 of three inferolateral LV segments  were significantly affected in patients with reduced GLS in univariate logistic regression. However, only longitudinal strain for segment number 5 was significantly reduced in patients with reduced GLS in multivariate logistic regression .p = 0.06)  and 1-specificity (0.12), and borderline significance ( = 0.06) .In this study, we evaluated the global longitudinal strain (GLS) of the left ventricle derived from feature tracking and the effect of T1 and T2 mapping, ECV, and LGE on GLS in patients who had recovered from COVID-19. CMR abnormalities, including myocarditis patterns, are common in patients who have recovered from COVID-19 and presented with protracted symptoms that could have resulted from cardiac involvement.Patients with GLS less negative than −15% had significantly lower LVEF and a significantly higher number of segments with prolonged T1.Left ventricular GLS was significantly positively correlated with T1 and significantly negatively correlated with LVEF.Left ventricular GLS less negative than −15% was 7.5 times more likely in patients with prolonged T1.Reduced longitudinal strain in the basal inferolateral segment had a significant effect on the global left ventricular longitudinal strain.ROC results suggested that a GLS of −14.5% predicted prolonged T1 relaxation time with the best combination of sensitivity and specificity.The main findings of this study are as follows:In our previous study, we evaluated the myocardial injury detected by TTE and CMR in healthcare workers recovering from non-severe COVID-19 . Left veThe efficacy of regional left ventricular systolic dysfunction assessed by longitudinal strain in echocardiography is well established in patients with myocarditis. Leitman et al. demonstrated a high correlation between regional longitudinal strain and LGE detection in the same left ventricular regions in patients with myocarditis . The invCMR is an imaging modality that can characterize the acute inflammatory myocardial process using a combination of scanning sequences that detect edema, hyperemia, and fibrosis. This combination of sequences represents the foundation of the Lake Louise criteria (LLC) . HoweverSeveral studies have investigated whether myocardial strain analysis could discriminate patients with acute myocarditis from healthy subjects and to what extent myocardial strain deformation is associated with other myocardial inflammatory parameters such as prolonged T1 and/or T2. It has also been extensively investigated which type of strain  provides the best value in the diagnostic process of patients with acute myocarditis ,34. GlobIn our study, GLS was also significantly correlated with T1 relaxation time. Overall, the evidence suggests that longitudinal strain can detect even mild myocardial dysfunction. The newer parameters of myocardial inflammation, especially T1 and T2 relaxation times, have a high diagnostic performance in detecting acute myocardial edema with excellent diagnostic accuracy . The facOur results suggest that regional inflammatory processes can lead to regional myocardial dysfunction. Therefore, segmental myocardial strain assessment can be considered a noninvasive parameter of regional myocardial injury in the course of the myocardial inflammatory process. Fisher et al. showed in their univariate analysis that GLS was significantly associated with major adverse cardiovascular events. In a multivariable model adjusted for clinical variables  and established CMR parameters (LVEF and LGE amount), LV global longitudinal strain remained independently associated with cardiovascular outcomes . The autTo our knowledge, the current study is the first to evaluate FT-derived left ventricular GLS in patients who recently recovered from COVID-19. The CMR-FT used in this study is a technique that has not yet been performed on a routine basis in the clinical setting. However, it may be an important tool for a more detailed characterization of myocardial injury and prognostication in this clinical scenario.One limitation of this study is that acute myocarditis was not confirmed by endomyocardial biopsy, although biopsy is not a standard diagnostic tool in all cases of suspected acute myocarditis. The strain analysis was also limited to global and segmental longitudinal strains, and no control group without COVID-19 infection was evaluated. Another important consideration is that in patients with cardiac symptoms, CMR provides a noninvasive and clinically useful differential diagnosis across a spectrum of myocardial disease, beyond myocarditis . TherefoCMR abnormalities, including a myocarditis pattern of nonischemic late gadolinium enhancement, are common findings in patients with prolonged symptoms who have recovered from COVID-19. Changes in CMR global and segmental longitudinal left ventricular strain are related to prolonged T1 relaxation time and may serve as a readily available novel parameter to detect global and regional myocardial injury and dysfunction in patients with suspected myocardial involvement after recovery from COVID-19, thus improving the global diagnostic potential of CMR, including facilities where newer quantitative techniques may not yet be available.


The outcomes of patients with acute ischemic stroke (AIS) are related to cardiac function. Cardiac insufficiency can manifest as hydrostatic changes in the lungs. Computed tomography (CT) of the chest is commonly used for screening pulmonary abnormalities and provides an opportunity to assess cardiac function.To evaluate the correlation between hydrostatic lung manifestations on chest CT and cardiac function with its potential to predict the short-term outcome of AIS patients.We retrospectively analyzed AIS patients who had undergone chest CT at admission and echocardiogram within 48 h. Morphological and quantitative hydrostatic changes and left ventricular dimensions were assessed using chest CT. Improvement in the National Institutes of Health Stroke Scale (NIHSS) score on the seventh day determined short-term outcomes. Multivariate analysis examined the correspondence between hydrostatic lung manifestations, left ventricular dimension, and left ventricle ejection fraction (LVEF) on echocardiography, and the correlation between hydrostatic changes and short-term outcomes.p < 0.05). Of the 204, 53 patients (26%) with varying degrees of hypostatic lung manifestations had less improvement in the NIHSS score (p < 0.05). The density ratio of the anterior/posterior lung on CT showed a significant negative correlation with improvement in the NIHSS score . Additionally, patients with a baseline NIHSS ≥4 with left ventricular enlargement had significantly lower LVEF than that of patients with normal NIHSS scores.We included 204 patients from January to December 2021. With the progression of hydrostatic changes on chest CT, the LVEF on echocardiography gradually decreased (Hydrostatic lung changes on chest CT can be used as an indicator of cardiac function and as a preliminary reference for short-term outcome in AIS patients. As the second most common risk factor for cardiogenic stroke after atrial fibrillation (AF), decreased left ventricular function is a major risk factor for functional outcomes of strokes . Heart fIn addition to decreased left ventricular ejection fraction (LVEF) and hypertensive cardiac remodeling, decreased left ventricular function can lead to elevated pulmonary artery pressure and microvascular filtration pressure in the lungs, which cause lung injury and promote fluid formation through hydrostatic mechanisms and changes in permeability . These pComputed tomography (CT) of the chest plays a valuable role in clinical screening, especially in emergency patients with unclear clinical histories , 11. CT This study aimed to evaluate the correlation between hydrostatic lung manifestations and cardiac changes on chest CT and the short-term outcomes for AIS patients to assess the efficacy of chest CT as a prognostic indicator.2.2.1.We retrospectively analyzed the medical records of AIS patients who had been admitted to our institution between January to December 2021. All patients underwent a standard set of brain CT scans  and chest CT immediately upon admission. Inclusion criteria for this study were as follows: (1) the diagnosis of ischemic stroke met the national and international criteria for acute stroke and the time of stroke onset was less than 6 hours (from the hyperacute period), and for patients who underwent echocardiography this occurred within 48 h after admission to rule out structural abnormality; (2) patients with first-ever ischemic stroke or no legacy effects of their previous ischemic stroke; and (3) patients who had received recanalization therapy (thrombolysis or thrombectomy) and no complications or adverse effects were noted. The exclusion criteria were as follows: (1) patients with chronic obstructive pulmonary disease, bilateral diffuse emphysema, pulmonary fibrosis, severe intrapulmonary infection, or lung cancer; and (2) patients with coronary stents, prosthetic heart valves, prior coronary artery bypass graft surgery, or metal artifacts in the region of the cardiac silhouette that affected image quality.On hospital admission, demographic data  were collected, and cardiovascular risk factors  were recorded. The National Institutes of Health Stroke Scale (NIHSS) was assessed at admission (baseline) and 7 days later. The water swallow test (WST) score was performed at admission to assess the degree of dysphagia (1) for ability to swallow the water continuously, (2) for ability to swallow the water more than twice without coughing or choking, (3) for voice quality or breathing pattern change, (4) for ability to swallow the water more than twice with coughing or choking, and (5) for inability to swallow , 14.2.2.All chest CT examinations were performed using a 256-detector row CT scanner . Chest CT was performed using a tube voltage of 100 kV and tube current modulation. Routine reconstruction of the chest CT images included axial images of 5 mm thickness with a high resolution and soft tissue algorithm, and axial images of 0.625 mm thickness with a high-resolution algorithm. The coronal images of the lung window were also reformatted. All the images were transferred to the picture archiving and communication system (PACS) server for image reading and further analysis.Image evaluation was performed by two experienced radiologists (with at least 3 years of experience in chest radiology). The radiologists were blinded to the clinical information and study outcomes. Dedicated monitors and workstations for image reading with multiplanar reformation capacity were used for image analysis.The imaging features of the lungs related to hydrostatic changes and other signs were evaluated and recorded, including small ill-defined opacities, interlobular septal thickening, ground-glass attenuation, airspace consolidation, and pleural effusion  15). Fo. Fo15). To assess the left ventricular (LV) dimensions, short-axis images of the left ventricle were reformatted using thin-slice images on the workstation. The maximum transverse diameter of the left ventricle, including the interventricular septum and lateral wall, was measured . LV enlaMeasurement of cardiac dimension and function was performed with trans-thoracic echocardiography using a clinical scanner (Philips IE33 or GE Vivid E95) by certified cardiologists or sonologists. LVEF and LV dimensions were recorded for comparison with chest CT features. Left ventricular internal diameter in diastole (LVIDd) >56 mm is defined as LV enlargement in males and LVIDd >51 mm in females .2.3.χ2 analysis or Mann–Whitney test in both mild and severe stroke groups. Frequency of hydrostatic signs in the lungs on the chest CT in AIS patients were calculated. Polyserial correlation coefficients were used to evaluate the association between continuous CT HU measurements, LV widest short-axis dimensions, and poor outcomes at 7 days. Multiple linear regression analysis was used to assess the related factors on the improvement of the NIHSS score. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of CT HU measurements for differentiation between improvement of ≤30% of the NIHSS score from admission to the seventh day.Interobserver agreement and various parameters measured using echocardiography or chest CT were assessed using the kappa coefficient statistical test. Differences in characteristics between patients with or without imaging signs were assessed by 3.3.1.A total of 204 patients were included in this study, with 81 and 123 in the mild and severe stroke groups, respectively. The demographic and clinical data of the two groups are presented in 3.2.p < 0.001) and a lower improvement in NIHSS on the seventh day (p < 0.001) compared to patients without lung changes or with only interlobular septal thickening  had abnormal lung CT findings and tended to have a lower proportion of NIHSS improvement in both the mild and severe stroke groups, both of which were statistically significant . The freickening –D.3.3.There were strong correlations between ΔA/P and LVEF measured using echocardiography, especially in the severe stroke group . In the The ROC analysis results of ΔA/P for determining an improvement of ≤30% of the NIHSS score from admission to the seventh day are shown in 3.4.p < 0.001). However, this difference was not significant in the mild stroke group (p = 0.962). Furthermore, ΔA/P measured on CT and the improvement of NIHSS score in seven days had no correlation with LV maximum short-axis dimension in both the mild and severe stroke groups , but patients with LV enlargement showed a higher ΔA/P (p < 0.001) and a lower NIHSS improvement (p < 0.001) in the severe stroke group , as shown in Excellent agreement between the two radiologists was achieved for the LV measurements (kappa = 0.807). The kappa statistic showed excellent agreement between CT and echocardiography for the definition of LV enlargement in both the mild and severe stroke groups (kappa = 0.633/kappa = 0.604). As shown in ke group ,J. Simil4.Cardiac function is associated with stroke occurrence and mortality , 21. PreThe primary findings of this study are as follows: (1) we observed a difference between improvement in early outcome among patients with and without presentation of morphological changes due to hydrostatic pressure, especially ground-glass attenuation in the lungs; (2) the ΔA/P showed a strong association with LVEF along with the improvement of outcome in 7 days. Moreover, ΔA/P had high sensitivity and specificity for differentiating patients with the potential to demonstrate >30% of baseline NIHSS score; and (3) patients from the severe stroke group demonstrating LV dilation had a higher ΔA/P and a poorer improvement in NIHSS score compared to patients without LV dilation (baseline NIHSS score >4).p < 0.001). AIS patients showing ground-glass attenuation or more severe hydrostatic changes suggestive of decreased cardiac function at presentation showed poor short-term improvement in the NIHSS score on the seventh day.Typical morphological changes due to hydrostatic pressure of the lung mainly include small ill-defined opacities, interlobular septal thickening, ground-glass attenuation, airspace consolidation, and pleural effusion. Previous studies have reported ground-glass attenuation in 25%–100% patients with hydrostatic edema. The lesions are mostly peribronchovascular owing to gravity , 27. In Previous studies support our findings of quantitative analysis of CT HU measurements in AIS patients, which suggest an altered cardiac function . RosenblIn addition to pulmonary manifestations, CT can provide information on cardiac structures that can reflect cardiac function. Previous studies have shown that LV dilation is an independent adverse predictor of cardiac function from other risk factors and is associated with an increased risk of clinical heart failure , 34. In 4.1.The major advantage of this study was that chest CT is an easily achievable tool for excluding coexisting pulmonary conditions without a significant delay in patient management. However, due to the preliminary nature of this study, it also entailed several limitations. First, our study only included patients with hyperacute AIS; therefore, pulmonary manifestations were less affected by other factors such as subsequent infection. Evaluation of patients at other stages should be conducted in future studies. Second, chest CT can only be used for the gross evaluation of cardiac function, and the parameters are mostly indirect indicators. However, previous studies have established a linear correlation between CT HU measurements and pulmonary capillary wedge pressure measurements, as well as the New York Heart Association functional classification of heart failure . Third, 5.A preliminary assessment of cardiac function can be achieved with qualitative and quantitative analyses of chest CT features, which can be used to predict short-term outcome in AIS patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the patients/participants or patients/participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.XD and JL conceived and designed the experiments. JB, CW, YZ, and ZS performed the experiments. JB, CW, and YZ analyzed the data. JB wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In recent years, cardiovascular disease has garnered increasing attention as the second leading cause of death in individuals with acromegaly, following malignancy. Identifying cardiac dysfunction early in acromegaly patients for timely intervention has become a focal point of clinical research. Speckle tracking echocardiography, a well-established ultrasound technique, surpasses conventional Doppler ultrasound in its sensitivity to assess both local and global cardiac mechanics. It can accurately detect subclinical and clinical myocardial dysfunction, including myocardial ischemia, ventricular hypertrophy, and valvular changes. Over the past five years, the use of speckle tracking echocardiography in acromegaly patients has emerged as a novel approach. Throughout the cardiac cycle, speckle tracking echocardiography offers a sensitive evaluation of the global and regional myocardial condition by quantifying the motion of myocardial fibres in distinct segments. It achieves this independently of variations in ultrasound angle and distance, effectively simulating the deformation of individual ventricles across different spatial planes. This approach provides a more accurate description of changes in cardiac strain parameters. Importantly, even in the subclinical stage when ejection fraction remains normal, the strain parameters assessed by speckle tracking echocardiography hold a good predictive value for the risk of cardiovascular death and hospitalization in acromegaly patients with concomitant cardiovascular disease. This information aids in determining the optimal timing for interventional therapy, offering important insights for cardiac risk stratification and prognosis. In the present study, we comprehensively reviewed the research progress of speckle tracking echocardiography in evaluating of cardiac dysfunction in acromegaly patients, to pave the way for early diagnosis of acromegaly cardiomyopathy. It is characterized by facial roughness and enlarged extremities due to excessive soft tissue growth and also associated with bone and joint lesions and related metabolic syndrome . The incThese cardiovascular complications include acromegalic cardiomyopathy, hypertension, arrhythmias, and valvular disease . AcromegEchocardiography presents a readily accessible technique for evaluating both structural and functional cardiac abnormalities . HoweverSpeckle tracking echocardiography (STE) emerges as a relatively recent ultrasound technique that allows quantitative analysis of both regional and overall myocardial motion and deformation. Importantly, it overcomes the well-documented limitations of Doppler ultrasound, including angle dependence, susceptibility to noise interference, and interobserver variability , 22. Cur2Speckle tracking ultrasound technology and traditional two- or three-dimensional digital echocardiography images, employ image processing algorithms to identify small and stable myocardial footprints or spots generated by the interaction between ultrasound waves and myocardial tissue in the selected region of interest. Tracking the distance between frames and spots or their spatial-temporal displacement  in each cardiac cycle, provides valuable information on focal, phased, and global myocardial strain . The con32D-STE is an innovative ultrasound technique that combines speckle tracking with two-dimensional ultrasound to assess longitudinal strain (LS), radial strain (RS), and circumferential strain(CS) associated with myocardial contractility that can occur at the myocardial level. This is in contrast to the left ventricular ejection fraction (LVEF), which is commonly used clinically to evaluate left ventricular systolic function but is less sensitive to subtle ultrastructural changes , 33–35. 3.1The use of 2D STE in patients with acromegaly is on the rise, with a primary focus on GLS as a key parameter for assessing changes in ventricular anatomical volume changes and kinematic alterations. Left ventricular function has always been a focal point of clinical research, thus warranting early exploration. Volschan ICM et al. were among the first to apply STE to assess cardiac function in acromegaly patients . Neverth3.2Only a limited number of studies have employed 2D STE to assess LA function in acromegaly patients. Uzibło-Życzkowska et al. used 2D STE to evaluate changes in LA and LV function parameters among acromegaly patients, and their findings indicated that GLS was significantly worse in these patients . This obThe LA serves multiple roles within the cardiac system, including acting as a cardiac reservoir, catheter, and booster pump . It also4Compared to 2D STE, the analysis of cardiac functional parameters using 3D STE offers several advantages. It is faster, demands less technical expertise, reduces interobserver variability, and enhances reproducibility . Further4.1In 2018, Kormányos et al. conducted pioneering research using 3D STE to investigate LV rotation patterns and mechanical changes in acromegaly patients. Their findings revealed significant alterations in LV basal, apical, and ventricular rotation parameters among patients with acromegaly . NotablyKormányos et al. used 3D STE to evaluate cardiac radial strain (RS), longitudinal strain (LS), circumferential strain (CS), and three-dimensional comprehensive strain (3DS) in active acromegaly patients . Their fTo date, no comprehensive study has explored the factors influencing LV deformation using 3D STE. Nemes A et al. attempted to use 3D STE to assess the effect of DM on LV rotation and deformation parameters in acromegaly patients . Their s4.2The LA functions as an auxiliary pump for the ventricle, undergoing physiological remodeling to support the ventricle’s ejection function during increased load. However, the magnitude of atrial enlargement is limited, and once pathological remodeling, such as fibrosis or atrial fibrillation occurs, reversal becomes unlikely. Thus, timely recognition and intervention for left atrial injury are of paramount importance . KormányPopielarz-Grygalewicz A et al. indicated that nearly 80% of acromegaly patients exhibit increased LAVi, whereas LVH is observed in less than 50% of patients. This suggests that adaptive LA remodeling takes precedence over LV remodeling in the cardiac progression of acromegaly patients. Furthermore, the study identified a negative correlation between LAVi and GLS, highlighting that the LA, functioning as a cardiac reservoir, catheter, and booster pump, shares a Frank-Starling regulatory mechanism similar to the LV. The LA and LV work in dynamic cooperation . Consequ4.3Limited research has investigated the functional parameters of RA in patients with acromegaly. Historically, the role of the RA has been characterized as ‘the first to live and the last to die, underscoring its pivotal role in maintaining normal blood supply to the heart. Using 3D STE for a quantitative assessment of RA function can greatly enhance our understanding of its function and remodeling . Kormány4.4The prevalence of heart valve disease in acromegaly patients approaches 75% , with mo5The primary treatments for acromegaly include surgery, drugs, and radiotherapy. Timely surgery serves as the cornerstone of early treatment, while drugs and radiotherapy are commonly employed as second-and third-line options when clinical remission is not achieved following surgical treatment. However, even after reaching the clinical remission target for GH, additional treatment for complications remains necessary . In gene6The STE can identify the changes of early atrioventricular motion pattern changes and evaluate myocardial strain parameters, offering valuable evidence of subclinical myocardial injury. This information is crucial for the clinical management and prognosis of cardiac dysfunction in acromegaly patients. However, since STE is a relatively recent technique, current research on its application to explore myocardial strain parameters in acromegaly patients is insufficient and long-term studies evaluating the predictive value of strain parameters are lacking. Further research is required to determine the accuracy of strain parameters in predicting the prognosis and survival outcomes of acromegaly patients. Nonetheless, we can affirm that the speckle tracking technique holds significant potential application prospects in acromegaly and cardiac dysfunction, representing a breakthrough in diagnosis. In clinical practice, the selection of imaging techniques depends on the indications and information requirements for a given case. Often, a combination of one or more imaging modalities is employed to achieve an accurate disease diagnosis. Commonly used cardiac imaging techniques for evaluating myocardial performance include echocardiography, CMRI, ventriculography, myocardial radionuclide imaging, and CT(Computed Tomography) Table 3.7This paper is a summary based on our own understanding of the literature and although we have tried to be as objective as possible in our analysis, we still cannot exclude a strong subjectivity. Also, this paper is only a summary of the application of STE in the acromegaly population, and the scope of discussion is narrow, so the results should not be interpolated to the general population, pending further expansion of the study population for comparative analysis. As STE has only begun to show its clinical application in the last decade, the number of relevant papers included in this article is limited, and more relevant studies are expected in the future to further explore the diagnostic value of STE in cardiac dysfunction in the acromegaly population.HL: Supervision, Writing – review & editing. RH: Data curation, Formal Analysis, Writing – original draft. JJ: Data curation, Formal Analysis, Writing – original draft. PZ: Data curation, Formal Analysis, Writing – original draft. KY: Methodology, Writing – review & editing. HZ: Investigation, Writing – review & editing. XC: Methodology, Writing – review & editing. WH: Methodology, Software, Writing – review & editing. HG: Methodology, Writing – review & editing. ZL: Supervision, Writing – review & editing. HX: Supervision, Writing – review & editing. YL: Supervision, Writing – review & editing.


Heart failure is a substantial and escalating global health challenge, affecting millions worldwide. This complex syndrome arises from diverse etiologies, encompassing ischemic heart disease, hypertension, valvular abnormalities, and cardiomyopathies. Heart failure is characterized by the heart's inability to pump blood efficiently to meet the body's metabolic demands, leading to debilitating symptoms, frequent hospitalizations, and high mortality rates. Traditionally, the management of Heart failure has focused on alleviating symptoms, reducing fluid retention, and enhancing cardiac contractility. These goals have been achieved through a combination of pharmacological therapies such as angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics, often complemented by device-based interventions like implantable cardioverter-defibrillators and cardiac resynchronization therapy. However, despite these advances, the relentless progression of heart failure remains a significant clinical challenge. Neurohormonal activation, cardiac fibrosis, and cellular remodeling are just a few of the intricate processes contributing to the disease's progression. In recent years, researchers and clinicians have embarked on a quest to identify novel therapeutic approaches that address these underlying mechanisms. One such avenue of exploration involves the revolutionary field of gene therapy, with promising gene-editing techniques, such as CRISPR-Cas9, offering potential routes for correcting genetic mutations that contribute to heart failure. Additionally, regenerative medicine approaches, including stem cell therapy and tissue engineering, hold significant promise for repairing damaged cardiac tissue and restoring function. Furthermore, precision medicine initiatives have gained traction, aiming to tailor heart failure therapies to individual patient profiles, taking into account genetics, biomarkers, and comorbidities. Integrating artificial intelligence and machine learning in heart failure management has also enabled the development of predictive models for early intervention, risk stratification, and personalized treatment recommendations. This narrative review navigates the intricate landscape of emerging therapies for heart failure, emphasizing their potential to revolutionize the field by targeting the disease's fundamental mechanisms. By exploring these innovative approaches, we aspire to provide a comprehensive perspective on the evolving paradigm of heart failure management, fostering a hopeful outlook for patients and clinicians alike. Heart failure is a rapidly growing global health issue that significantly impacts individuals and healthcare systems around the globe. The disease in question is characterized by its intricate and diverse nature, resulting in a notable reduction in the overall well-being of those affected, as well as imposing a significant financial strain. This narrative review explores the crucial subject of "Advancements in Heart Failure Management," with a particular emphasis on developing therapies that have the potential to impact the field of heart failure care significantly. The significance of this narrative review resides not only in the critical assessment of emerging therapeutic strategies but also in the acknowledgment of heart failure as a significant public health concern necessitating innovative resolutions. To fully comprehend the importance of breakthroughs in heart failure management, it is imperative to grasp the scale and gravity of the issue. Heart failure significantly impacts many individuals globally, with around 64 million affected. Moreover, the prevalence of this condition is steadily increasing. The increase in occurrences of heart failure can be partially linked to the aging population and a higher incidence of cardiovascular risk factors such as hypertension, diabetes, and obesity . Heart fNotwithstanding these noteworthy therapeutic advancements, heart failure continues to pose substantial obstacles. Notwithstanding the availability of current medicines, it is essential to acknowledge that not all patients exhibit ideal responses, and the disease frequently exhibits a persistent progression. The management of medical conditions can be further complicated by adverse effects, medication intolerances, and non-adherence to complex drug regimens . A signiThis narrative review thoroughly examines these emerging medicines, exploring their potential to transform heart failure management fundamentally. This review seeks to contribute to the existing knowledge on heart failure by comprehensively examining recent advancements and their potential consequences. The ultimate goal is to stimulate innovation and progress within the area. This study aims to thoroughly analyze the diverse developing medicines in managing heart failure, thoroughly examining their underlying mechanisms of action, clinical efficacy, and prospective benefits compared to established therapy modalities. Every developing therapy will undergo a rigorous evaluation, assessing its merits and inherent constraints. A comprehensive review of these therapeutic approaches will give physicians and researchers valuable insights to facilitate informed decision-making on their integration into clinical practice. The narrative review will finish by proposing prospective avenues for future study and advancement in heart failure management. Identifying topics necessitating further inquiry can serve as a valuable tool in guiding future research endeavors and promoting a culture of ongoing innovation. This narrative review aims to explore the diverse range of developing therapeutics for heart failure to provide a thorough examination of the breakthroughs that show potential in transforming the treatment of this widespread global health issue.MethodsSearch StrategyA comprehensive search strategy was employed to ensure the comprehensiveness and rigor of this narrative review. Databases, including PubMed, Embase, Scopus, and Web of Science, were systematically searched for relevant articles, reviews, and clinical studies published up to this review's commencement (September 2023). Keywords such as "heart failure," "emerging therapies," "pharmacological advancements," "device-based interventions," "regenerative medicine," and "precision medicine" were utilized in various combinations to identify pertinent literature.Inclusion and Exclusion CriteriaInclusion criteria were established to select articles that align with the scope of this narrative review-including studies and articles needed to focus on emerging therapies in heart failure management, covering various aspects such as pharmacological innovations, device-based interventions, regenerative medicine, and precision medicine. Articles critically evaluating emerging therapies and their potential impact on clinical practice were prioritized. Exclusion criteria were applied to exclude articles that did not meet the specified scope, were not written in English, or were not peer-reviewed. Additionally, studies solely focused on basic science research without clinical relevance were excluded.Data SynthesisData synthesis was performed by categorizing the emerging therapies into thematic groups, such as pharmacological advancements, device-based interventions, regenerative medicine, and precision medicine. Each category was analyzed individually, focusing on summarizing the mechanisms of action, clinical effectiveness, strengths, and limitations of the therapies.Ethical ConsiderationsThis narrative review adheres to ethical principles and guidelines for conducting systematic and narrative studies. No primary data collection from human subjects was performed for this review; therefore, ethical approval was not required. However, ethical considerations related to the use of patient data in the included studies were discussed where applicable.LimitationsIt is essential to acknowledge that narrative reviews, while valuable for synthesizing existing knowledge, are subject to limitations such as selection bias in article inclusion and potential bias in data interpretation. Efforts have been made to minimize these limitations through a systematic and transparent methodology.Understanding heart failureHeart failure is a multifaceted and debilitating clinical syndrome characterized by the heart's inability to pump blood effectively to meet the body's metabolic demands. It represents a significant global health challenge, impacting millions of individuals and straining healthcare systems worldwide. This comprehensive article aims to provide an extensive overview of heart failure, encompassing its definition, epidemiology, classification, and pathophysiology. It will also delve into the multifactorial nature of the disease and its challenges. Heart failure, also known as congestive heart failure, is a complex clinical syndrome marked by the heart's compromised ability to pump blood efficiently, resulting in inadequate circulation and oxygen delivery to meet the body's metabolic requirements. It is not a singular disease entity but rather a syndrome that arises from various cardiovascular and non-cardiovascular factors.Epidemiology of Heart FailureHeart failure is a pervasive health concern that affects millions of people worldwide. Its prevalence continues to rise, driven by aging populations, improved survival following heart attacks, and an increasing burden of risk factors, including hypertension, diabetes, and obesity. In the United States, it was estimated that approximately 6.2 million adults aged 20 and older had heart failure in 2019 .Moreover, heart failure is a leading cause of hospitalization among older adults, resulting in a significant economic burden on healthcare systems . The ecoClassification of Heart FailureHeart failure with reduced ejection fraction (HFrEF) vs. heart failure with preserved ejection fraction (HFpEF). HFrEF is defined by a left ventricular ejection fraction (LVEF) of less than 40%. It is often associated with impaired heart muscle contractile function and is more commonly attributed to conditions such as ischemic heart disease, cardiomyopathies, or myocarditis. HFpEF patients exhibit an LVEF more significantly than 50%. HFpEF is associated with impaired relaxation and increased left ventricle stiffness, often occurring in the context of hypertension, diabetes, or aging . AcknowlPathophysiologyUnderstanding the pathophysiology of heart failure is paramount for effective diagnosis and management. It involves a complex interplay of various factors, including structural, functional, and neurohormonal changes in the heart. In most cases of heart failure, there is a process known as left ventricular remodeling. This process involves alterations in the left ventricle's size, shape, and structure, often resulting from myocardial infarction, hypertension, or chronic volume overload. These structural changes can impair contractility and reduce stroke volume . ChronicNeurohormonal ActivationIn response to reduced cardiac output, the renin-angiotensin-aldosterone system (RAAS) is activated. This leads to increased levels of angiotensin II and aldosterone, which cause vasoconstriction and sodium and water retention, ultimately increasing cardiac workload and exacerbating heart failure. Sympathetic nervous system (SNS) activation is another compensatory mechanism in heart failure. It leads to increased heart rate, contractility, and vasoconstriction, all of which are initially beneficial but can become detrimental in the long term . In respMultifactorial Nature of Heart FailureHeart failure is not a single disease entity; it is the final common pathway of various cardiac and non-cardiac conditions. This multifactorial nature makes both diagnosis and treatment complex. Coronary artery disease, myocardial infarction, and chronic ischemia significantly contribute to heart failure, particularly HFrEF. Dilated, hypertrophic, and restrictive cardiomyopathy can lead to heart failure. Conditions such as aortic stenosis and mitral regurgitation can overload the heart and eventually result in heart failure. Severe and poorly controlled arrhythmias can disrupt normal heart function and contribute to heart failure . ChronicCurrent treatment landscapeThe management of heart failure has evolved significantly over the past few decades, focusing on alleviating symptoms, improving quality of life, reducing hospitalizations, and prolonging survival. Treatment strategies are tailored to the type and stage of heart failure, with a primary division between HFrEF and HFpEF. This section will explore the existing treatments and management strategies for heart failure, including pharmacological interventions, device-based therapies, and lifestyle modifications. Additionally, it will highlight the limitations of current treatments and emphasize the ongoing need for innovation in heart failure management.Pharmacological InterventionsACE inhibitors have been a cornerstone in treating HFrEF. They reduced the production of angiotensin II, a potent vasoconstrictor, and aldosterone, leading to vasodilation and decreased sodium and water retention. Essential drugs in this class include enalapril, lisinopril, and ramipril. The landmark CONSENSUS trial demonstrated the significant mortality reduction of enalapril in patients with severe heart failure . ARBs, sDevice-Based TherapiesICDs are recommended for select HFrEF patients at risk of sudden cardiac death, particularly those with a history of ventricular tachycardia or fibrillation. ICDs monitor the heart's rhythm and deliver shocks when life-threatening arrhythmias occur. CRT involves the implantation of a biventricular pacemaker to synchronize the contraction of the heart's ventricles. It benefits HFrEF patients with intraventricular conduction delays, improving symptoms and reducing mortality . Left veHeart TransplantationHeart transplantation is considered the ultimate therapy for end-stage heart failure when medical and device-based treatments are no longer effective. However, donor organ scarcity limits its availability.Lifestyle Modifications and Non-Pharmacological ApproachesDietary sodium restriction is a critical component of heart failure management. Limiting sodium intake helps reduce fluid retention and congestion, alleviating symptoms. Fluid restriction is often recommended to manage fluid overload in advanced heart failure. Patients are advised to monitor daily fluid intake carefully. For obese patients with heart failure, weight management and lifestyle changes are crucial. Achieving and maintaining a healthy body weight can improve heart function and reduce symptoms . RegularLimitations of Current TherapiesMany medications and device-based therapies have shown remarkable benefits in HFrEF but have limited efficacy in HFpEF, for which there is currently no disease-modifying therapy. Drugs such as ACE inhibitors and beta-blockers can cause side effects, including hypotension, renal dysfunction, and hyperkalemia, necessitating careful monitoring. Some patients may develop tolerance or resistance to medications over time, necessitating dosage adjustments or the addition of alternative therapies. Device-based therapies, such as LVADs and ICDs, carry risks of complications, including infections, bleeding, and device malfunction. Access to advanced treatments such as heart transplantation and LVADs is limited by donor organ availability and cost considerations . SuccessOngoing Need for InnovationAdvancements in precision medicine may lead to tailored therapies based on an individual's genetic, molecular, and clinical profile. This approach can optimize treatment efficacy while minimizing side effects. The search for novel pharmacological agents continues, with ongoing research into drugs targeting specific molecular pathways involved in heart failure pathophysiology . BiomarkPharmacological innovationsHeart failure is a complex and prevalent cardiovascular syndrome with a substantial global burden. Despite significant progress in treatment options, managing heart failure remains challenging due to its multifactorial etiology and diverse clinical manifestations. In recent years, pharmacological innovations have played a crucial role in improving the prognosis and quality of life for patients with heart failure. This section will discuss the latest advancements in pharmacological therapies, focusing on novel drug classes, mechanisms of action, and clinical trial findings.Novel Drug ClassesSodium-glucose co-transporter 2 (SGLT2) inhibitors, originally developed for treating diabetes mellitus, have emerged as a groundbreaking class of drugs in heart failure management. These medications, including empagliflozin, dapagliflozin, and canagliflozin, work by inhibiting glucose reabsorption in the renal proximal tubules, leading to glycosuria and improved glycemic control in diabetic patients. However, their benefits in heart failure go beyond glycemic control. SGLT2 inhibitors exert several beneficial effects on the cardiovascular system. They promote diuresis and natriuresis, reducing blood volume and cardiac preload. Additionally, they improve myocardial energetics by increasing the utilization of ketone bodies as an alternative fuel source for the heart. Furthermore, SGLT2 inhibitors reduce oxidative stress and inflammation while improving endothelial function . The EMPClinical Implications and GuidelinesThe emergence of these novel drug classes has profoundly impacted heart failure management and prompted updates to clinical guidelines. Here, we explore these innovative pharmacological therapies' clinical implications and guideline recommendations. The remarkable benefits of SGLT2 inhibitors in heart failure have led to their inclusion in clinical guidelines. The American College of Cardiology (ACC) and American Heart Association (AHA) 2021 guidelines for managing heart failure recommend using SGLT2 inhibitors in patients with HFrEF, irrespective of their diabetic status. Specifically, dapagliflozin and empagliflozin are recommended to reduce the risk of heart failure, hospitalization, and cardiovascular death . These gChallenges and ConsiderationsWhile these novel pharmacological innovations offer promising therapeutic options for heart failure patients, several challenges and considerations must be addressed. The cost of these innovative medications may pose a barrier to access for some patients, particularly in healthcare systems with limited resources. Ensuring affordability and equitable access to these therapies is essential to maximize their impact on heart failure outcomes. Optimal patient selection is crucial to realizing the benefits of these drugs while minimizing potential risks . CliniciDevice-based interventions in heart failure managementIn addition to pharmacological innovations, device-based interventions have been pivotal in advancing heart failure management. These interventions encompass a wide range of technologies, including implantable devices, remote monitoring systems, and artificial intelligence (AI) applications. This section explores the role of innovative devices in heart failure management and their impact on patient outcomes.Implantable DevicesCRT involves the implantation of a specialized pacemaker with the capacity to simultaneously pace both the left and right ventricles. CRT is primarily indicated for heart failure patients with dyssynchrony, characterized by delayed or uncoordinated contraction of the ventricles. CRT aims to synchronize ventricular contraction, which can significantly improve cardiac function in patients with left bundle branch block or intraventricular conduction delays. By optimizing the timing of ventricular contractions, CRT enhances stroke volume, reduces mitral regurgitation, and increases cardiac output . CRT hasVentricular Assist Devices (VADs)Ventricular assist devices (VADs) are mechanical pumps implanted in patients with advanced heart failure as a bridge to transplant or destination therapy. They can assist the weakened heart by pumping blood from the left ventricle to the aorta, augmenting cardiac output. VADs are designed to provide circulatory support, reducing the workload on the failing heart. Depending on the type of VAD, they can support the left ventricle, right ventricle, or both. VADs are used in patients with end-stage heart failure when other treatments have failed . VADs caRemote MonitoringRemote patient monitoring (RPM) involves using technology to track a patient's health status and transmit data to healthcare providers without frequent in-person visits. RPM is particularly relevant in heart failure management, enabling proactive monitoring of vital signs, symptoms, and medication adherence. RPM systems typically consist of wearable devices, such as wireless scales, blood pressure cuffs, and smartphones, that collect metrics like weight, blood pressure, heart rate, and oxygen saturation. This data is transmitted securely to healthcare providers, allowing for early detection of patient condition changes . RPM hasImplantable Hemodynamic MonitorsImplantable hemodynamic monitors are small devices implanted in the pulmonary artery. They continuously measure pulmonary artery pressures, providing real-time data on a patient's hemodynamic status. This information can guide treatment decisions and help prevent heart failure exacerbations. Implantable hemodynamic monitors use a wireless sensor to measure pressures in the pulmonary artery. Changes in these pressures can indicate worsening heart failure. Data from the sensor are transmitted to a remote monitoring system accessible by healthcare providers . StudiesArtificial Intelligence ApplicationsMachine learning (ML) and AI have gained traction in heart failure management for risk prediction. ML algorithms can analyze vast datasets, including clinical, imaging, and laboratory data, to identify patterns and predict which patients are at higher risk of heart failure exacerbations. ML models are trained on large datasets to recognize subtle ways and associations that may not be apparent to human clinicians. These models can integrate various data sources, such as electronic health records, wearable device data, and genetic information, to generate risk scores and identify patients who may benefit from more intensive monitoring or interventions . ML-baseClinical Implications and GuidelinesDevice-based interventions and AI applications have introduced transformative approaches to heart failure management. CRT, ICDs, and VADs have well-established roles in heart failure management. Clinical guidelines, such as those from the American College of Cardiology, American Heart Association, and European Society of Cardiology, provide recommendations on patient selection and appropriate use of these devices. These guidelines emphasize the importance of multidisciplinary heart failure teams to evaluate patients for device therapy and ensure optimal outcomes . Remote Regenerative medicine and stem cell therapy in heart failureHeart failure is a complex and debilitating condition characterized by the inability of the heart to pump blood effectively, leading to symptoms such as fatigue, shortness of breath, and fluid retention. It is a primary global health concern with limited treatment options, particularly for patients with advanced disease . In receStem Cells and Cardiac RegenerationStem cells are undifferentiated cells with the unique ability to differentiate into various cell types and promote tissue repair and regeneration. Embryonic stem cells (ESCs) are pluripotent stem cells derived from early-stage embryos. They can differentiate into all cell types, including cardiomyocytes, the specialized muscle cells of the heart. When introduced into the damaged heart, ESCs can develop into new cardiomyocytes, replacing the damaged tissue and improving cardiac function. Additionally, they may exert paracrine effects by releasing growth factors and cytokines that promote tissue repair . The useCurrent Status of Stem Cell Therapy in Heart FailureWhile stem cell therapy holds great promise for heart failure treatment, it is essential to acknowledge the current status of these therapies in clinical practice. Many clinical trials have demonstrated the safety and feasibility of stem cell-based interventions in heart failure. These studies have shown that stem cell transplantation, including autologous (patient's own) and allogeneic (donor-derived) cells, is generally well-tolerated and associated with low rates of adverse events. Some clinical trials have reported functional improvements in heart failure patients treated with stem cells. These improvements include increased LVEF, reduced ventricular remodelling, and enhanced exercise capacity . The outFuture Directions in Stem Cell TherapyDespite the challenges, stem cell therapy remains promising for heart failure treatment. Ongoing research efforts aim to address the limitations and optimize the therapeutic potential of stem cells. Future directions in stem cell therapy for heart failure include. Advances in iPSC technology enable the generation of patient-specific cardiomyocytes. These cells can be used for disease modeling, drug testing, and potentially autologous transplantation, offering a personalized approach to heart regeneration . CombiniClinical implementation and challengesImplementing emerging therapies in clinical practice presents challenges and hurdles across various domains, including cost, accessibility, and ethical considerations. These challenges are pivotal factors influencing the successful integration of innovative medical treatments into the healthcare ecosystem. This discussion will explore these challenges in-depth, emphasizing their significance and impact. One of the most prominent challenges of implementing emerging therapies is their substantial financial burden. Developing novel therapies is a lengthy and expensive process. Pharmaceutical companies invest significant resources in research, preclinical studies, and rigorous clinical trials to bring innovative treatments to the market. These development costs are eventually reflected in the price of the therapies . EmerginAccess ChallengesEnsuring equitable access to emerging therapies represents a significant challenge in healthcare. Geographic location can significantly influence access to emerging therapies. Patients in urban areas with well-funded healthcare systems may have more extensive access to cutting-edge treatments than those in rural or underserved regions, where healthcare infrastructure may be less robust . Access Ethical ConsiderationsThe ethical dimensions of implementing emerging therapies in clinical practice are multifaceted and require careful consideration. Obtaining informed consent is a fundamental moral requirement in healthcare. Patients must receive clear, understandable information about emerging therapies, including potential risks, benefits, and alternatives. The novelty and complexity of these treatments can pose challenges in achieving fully informed consent. Many emerging therapies involve collecting and analyzing sensitive patient data, including genetic information and personal health records. Ensuring the privacy and security of this data is paramount, and healthcare institutions and researchers must implement robust data protection measures . The allClinical implications and future directionsEmerging therapies in managing heart failure hold substantial promise, with the potential to profoundly impact patient care, clinical decision-making, and the broader landscape of heart failure management. This discussion delves into these therapies' clinical implications and explores future research and development directions.Clinical ImplicationsIntegrating emerging therapies into the clinical management of heart failure carries several significant clinical implications. Emerging therapies enable the tailoring of treatment plans to individual patient profiles. Healthcare providers can utilize genetic information, biomarkers, and clinical data to select the most appropriate therapies and monitor their effectiveness. This personalized approach can improve outcomes and reduce the risk of adverse events. Precision medicine facilitated by emerging therapies allows for more accurate risk prediction and early intervention. By identifying patients at higher risk of heart failure exacerbations or adverse outcomes, healthcare providers can proactively adjust treatment strategies and lifestyle recommendations to prevent complications. Emerging therapies, including novel drugs and stem cell-based treatments, offer the possibility of targeted interventions that address the underlying mechanisms of heart failure. As our understanding of the disease's molecular basis deepens, we can expect the development of more precise and effective treatments . Data-drFuture DirectionsAs emerging therapies continue to evolve, several future directions and areas of research and development can be anticipated. AI and machine learning algorithms can analyze vast datasets to identify complex patterns and predict patient outcomes . These tIn conclusion, this review has highlighted the multifaceted nature of heart failure management, exploring its complexities, challenges, and promising innovations. The key takeaways underscore the transformative potential of ongoing advancements in heart failure management. These developments offer hope for patients facing this challenging condition, from novel pharmacological interventions to innovative device-based therapies, regenerative medicine, and precision care. These advancements enable tailored treatment plans, precise risk prediction, and a shift towards more patient-centric care. The fusion of data-driven clinical decision-making, multidisciplinary collaboration, and patient empowerment promises improved outcomes and enhanced quality of life for individuals with heart failure. As we navigate the challenges of cost, accessibility, and ethical considerations, it is clear that the pursuit of emerging therapies and precision medicine in heart failure management is not only a scientific endeavor but also a moral imperative. The future of heart failure care holds the potential to redefine the patient experience, reduce disparities, and, ultimately, save lives. With ongoing research and dedication, we can look forward to a brighter horizon for heart failure patients and a revolutionized care landscape.


The management of chronic heart failure over the past decade has witnessed tremendous strides in medical optimization and device therapy including the use of left ventricular assist devices (LVAD). What we once thought of as irreversible damage to the myocardium is now demonstrating signs of reverse remodeling and recovery. Myocardial recovery on the structural, molecular, and hemodynamic level is necessary for sufficient recovery to withstand explant and achieve sustained recovery post‐LVAD. Guideline‐directed medical therapy and unloading have been shown to aid in recovery with the potential to successfully explant the LVAD. This review will summarize medical optimization, assessment for recovery, explant methodologies and outcomes post‐recovery with explant of durable LVAD. Myocardial recovery on the structural, molecular, and hemodynamic levels is necessary to withstand the explant for sustained recovery postleft ventricular assist device. Guideline‐directed medical therapy and unloading can aid in this process. This review will summarize evidence for reverse remodeling and myocardial recovery, and propose a protocol for optimization and assessment of myocardial recovery. Serious adverse events of stroke, bleeding, and pump thrombosis were less frequent in the centrifugal‐flow pump group. As a result of longer support with less adverse events, we began to observe signs of myocardial recovery in some patients. This prompted further investigation into what constitutes myocardial recovery and factors contributing to “reversibility of myocardial dysfunction” in LVAD patients. Despite the rate of true recovery remaining low with a lack of evidence for its sustainability, developing a better understanding of what underlies myocardial recovery has become a major research focus in the field.The 5‐year Kaplan–Meier estimate of survival was 58.4% in the centrifugal‐flow group versus 43.7% in the axial‐flow group  data, cardiac recovery during long‐term LVAD therapy is reportedly as low as 1.3%.Medical optimization with the goal of reverse LV remodeling should be considered in all patients supported with an LVAD. It is recommended that algorithms should be based on consensus documents for the use of GDMT, as per the 2021 update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment.https://clinicaltrials.gov/ct2/show/NCT05278962). It would be interesting to see if there is an added benefit to reverse remodeling and recovery.There is limited data on angiotensin receptor‐neprilysin inhibitor (ARNI); however, the available data is promising. A single center analysis of 30 LVAD patients on ARNI showed a significantly lower NT‐proBNP level at 6 months and better control of blood pressure.Mechanical unloading of the failing heart is associated with changes at the structural, molecular, and cellular levels; all of which have been linked to functional improvement.LVAD unloading also leads to a decrease in circulating levels of many neurohormones .Simon et al.Finally, the process of reconditioning after unloading has also been observed. This entailed a slow decrease in speed once the aortic valve opening time reached 10% of the cardiac cycle at a low speed of 6000 for HMII representing signs of reverse remodeling.33.1The addition of standard GDMT to LVAD supports augments the suppression of neurohormonal activity, further promoting a reversal of LV structural changes; however, since the initial studies on reverse remodeling and myocardial unloading following LVAD support, there were concerns that complete normalization of both anatomic shape and function along with the reversal of the molecular changes are not achieved. This is coupled with the fact that only a few patients achieve resolution of the adverse neurohormonal status after LVAD explantation.After discontinuation of LVAD support, the risk of recurrent HF and other cardiovascular events has been shown to be highest in the first year. Long‐term survival free from LVAD, transplant, or death after LVAD explanation for myocardial recovery is reported ~90% at 1 year and 77% at 3 years postexplant.As discussed above, 50% of the patients in the RESTAGE‐HF (Remission from Stage D HF) study,In a recent systematic review of 44 studies (85 patients) examining patient outcomes of device withdrawal by minimally invasive pump decommissioning as compared to reoperation for pump explantation, there were similar rates of patient survival, driveline infection, and cerebrovascular accidents at a median follow‐up of 1 year.In another evaluation of 53 patients, weaned patients with end‐stage NICM post‐LVAD wean as the underlying cause for VAD implantation revealed 5‐ and 10‐year postexplant survival probabilities  of 72.8 ± 6.6% and 67.0 ± 7.2%, respectively.Thus, the survival probability of our LVAD‐explanted patients with NICM as the underlying cause for LVAD implantation was better than that of patients with the same underlying cardiac disease who could not be weaned from their LVAD. Postexplant HF recurrence appears to be related to the duration of HF before LVAD implantation, and a preimplant history of HF > 5 years can be a relevant risk factor for postweaning HF recurrence.p = .76). Kaplan–Meier estimates of transplant‐free survival after VAD removal revealed probabilities of 68.9 ± 7.6% and 61.6 ± 8.6% for 5‐ and 10‐year survival, respectively. The complications related to VAD removal were uncommon. Infection was a major problem in five patients, but in four of these, it was already present before VAD removal.In a study by Dandel et al.,To date, postweaning recurrence of HF occurred in 17 (36.2%) of the evaluated patients suffering from CM before VAD implantation. Myocardial dysfunction with progressive LV dilation but not the new appearance or aggravation of pre‐existing mitral regurgitation (MR) appeared to be the cause for the recurrence of HF symptoms. Kaplan–Meier estimates revealed a probability of 66.0 ± 8.2% for 5‐year freedom from HF recurrence after VAD removal. In the patient group that underwent VAD removal before March 2002, HF recurred in 14 (45.2%) of 31 patients. Of these HF recurrences, nine (64.3%) occurred during the first year after weaning. In the group weaned thereafter, only three (18.8%) of the 16 patients showed HF recurrences, which all arose late, beyond the fourth postweaning year. There were no significant differences in postweaning cardiac stability between patients who were weaned from continuous flow LVADs and those weaned from pulsatile LVADs. Of the 17 patients with HF recurrence, 15 underwent HTx, one patient (65 years of age at HF recurrence) received another LVAD designed as a chronic mechanical circulatory support, and two patients died suddenly at 2.1 and 5.7 years after LVAD removal, respectively.4According to INTERMACS, 26% of patients with LVADs were listed for cardiac transplantation (bridge to transplant—BTT), 43% as destination therapy (DT), and 30% as bridge to decision. However, less than 1% of patients had sufficient recovery of LV systolic function to lead to LVAD explantation.p < .0001). In a cohort of 190 patients with LVADs, a weighted score was developed (I‐CARS score) to effectively stratify patients based on their probability of recovery. INTERMACS Cardiac Recovery Score (I‐CARS) was validated and exhibited good performance . Those who met the I‐CARS criteria were reported in INTERMACS to have an 86% 1‐year survival after LVAD explant. A total of 21 patients  achieved myocardial recovery.Independent predictors of recovery include: age <50 years, etiology of nonischemic cardiomyopathy, and time from cardiac diagnosis <2 years, absence of implantable cardiac defibrillators, creatinine ≤1.2 mg/dL, and LVEDD < 6.5 cm  was recently published. It involved a standardized approach to both the evaluation for recovery and the weaning of LVAD support. Forty patients with HMII LVADs were enrolled from six centers. All with nonischemic CM and LVEF < 25% preimplant and HF duration <5 years.1.LVEDD < 60 mm, LV end‐systolic dimension < 50 mm, LVEF > 45%.2.LV end‐diastolic pressure or pulmonary capillary wedge pressure ≤15 mm Hg.3.2.Resting cardiac index > 2.4 L/min/m4.Optional—Maximal oxygen consumption with exercise >16 mL/kg/min.Explant patients had to meet the following criteria measured at speeds of 6000 rpm for 15 min:Approximately 50% of the patients enrolled in RESTAGE HF were able to be weaned successfully and survival free from LVAD or transplantation in those explanted was 90% at 1 year and 77% at 2 and 3 years.https://classic.clinicaltrials.gov/ct2/show/NCT04069156). In Figure It is important to note that current device and medical therapy has evolved and we do not have enough data with HM3 devices and patients on GDMT that includes Entresto and Jardiance regarding myocardial recovery/remission. HM3 devices have a much more favorable hemocompatibility profile and there may be higher tolerance to speed lowering as far as a thromboembolic event rate in these patients. A randomized clinical trial—ARIES—is underway to compare the vitamin K antagonist regimen with aspirin versus vitamin K antagonist with placebo. The ARIES HM3 pump IDE study  must be corrected for suitable function of the LVAD.The correction of tricuspid regurgitation (TR) remains controversial. While regaining competency of the tricuspid valve at the time of device implant leads to shorter durations of inotropic support and hospital length of stay, there is no improvement in outcome as compared to LVAD implant alone in the BTT and DT populations.In HF, due to remodeling of the LV caused by annular dilatation, papillary muscle distortion, and chordal tethering, MR is commonly encountered.The extent of surgical intervention at the time of LVAD explant after recovery must also be considered. Cardiopulmonary bypass without cardiac arrest is utilized to support the heart at the time of explanation. Surgical planning and approach for successful LVAD explant must also include addressing any thrombus that may be present in the left ventricle as well as enduring structural heart issues.The surgical team must decide to approach the explant of the LVAD through a redosternotomy or through minimally invasive approaches. A redosternotomy is associated with increased blood transfusion requirements and injury to the heart that may threaten the success of LVAD explant of a recovered heart, so adaptation of minimally invasive techniques of LVAD explant has occurred. Minimally invasive approaches to repair the left ventricular apex will commonly utilize femoral and outflow graft arterial access and femoral venous access for cardiopulmonary bypass without cardiac arrest.When explanting the LVAD, closure of the defect in the LV must occur utilizing an apical plug, a patch, or primary closure. The defect in the LV apex for the inflow may be repaired primarily after explant by approximating the muscular edges of the LV with a series of interrupted sutures or with a running suture line. When a flexible sewing ring has been utilized at the time of LVAD implant, the edges of the sewing ring may provide a buttress for the suture line. For less flexible sewing rings, the sewing ring may be removed and the defect in the LV apex for the inflow may be repaired primarily or the sewing ring may be left in place and the defect in the LV apex for the inflow may be closed using a plug fashioned from surgical felt with or without a biologic covering or cap. The plug is positioned within the sewing ring and secured eliminating the need for an extensive LV repair. A more rigid sewing ring left in place and closed with a plug will provide access if the LVAD needs to be replaced.When embracing minimally invasive surgical techniques, complete removal of the device and outflow graft is far more complex and potentially not possible. Therefore, retention of portions or of the entire pump with inflow and outflow grafts may be necessary. To avoid a midline sternotomy, multiple smaller incisions overlying key components of the LVAD may be made to access the LVAD, inflow, and outflow cannula. When the outflow graft has been used for arterial access for cardiopulmonary bypass, the graft may be oversewn or stapled at the cannulation site leaving a small, retained portion of the outflow graft. The most minimally invasive technique described avoids cardiopulmonary bypass and involves leaving the entire LVAD intracorporeally and cutting the driveline. This results in a contained pump thrombus. When complete removal of the device and outflow graft is not accomplished, rare complications such as infection of the residual graft material or thromboembolic incidents have the potential to occur.77.1The pioneering work of Birks et al.8There are currently no consensus recommendations for antiplatelet or anticoagulation for patients who undergo LVAD explantation or decommissioning following either myocardial recovery or a device‐related complication. In a recent scoping review, 15 studies were identified that outlined anticoagulation strategies with regimens consisting of combinations of vitamin K antagonists, and unfractionated heparin and/or bivalirudin.Other complications have also been reported including infection and recurrent HF. Sepsis and driveline infections were reported and in one case leading to complete LVAD explantation. These are similar findings to the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) study, which included 45 patients, with a median follow‐up period of 26 months following LVAD explantation and reported one patient death due to sepsis. As long‐term results postexplantation or decommissioning become available, reliable parameters to predict outcomes can be identified.9The HF pandemic continues to grow as does the data showcasing the benefits of ventricular assist devices. The significant improvement in morbidity and mortality provoked the continued technological development of these devices aimed at improving the adverse event risk profile. As technology continues to evolve the focus on these devices as catalysts to recovery along with GDMT and other structural and electrophysiological interventions is of the essence. This entails both early assessment of potential for recovery and early utilization before end‐organ dysfunction, and further remodeling to myocytes occurs. Changing the VAD communities' approach to VAD support will lead to further recovery and remission. In summary, LVAD therapy combined with GDMT can facilitate remission and in some cases lead to partial or full myocardial recovery. In this review, we have included a pathway for cardiac‐assisted remodeling utilizing GDMT, unloading and reloading. Furthermore, we defined criteria and methodologies for explant and maintenance of remission.The authors declare no conflict of interest.