The gut microbiota and its metabolites have become a hotspot of recent research. Trimethylamine N-oxide (TMAO) metabolized by the gut microbiota is closely related to many diseases such as cardiovascular disease, chronic kidney disease, type 2 diabetes, etc. Chronic kidney disease (CKD) is an important contributor to morbidity and mortality from non-communicable diseases. Recently, increasing focus has been put on the role of TMAO in the development and progress of chronic kidney disease. The level of TMAO in patients with chronic kidney disease is significantly increased, and a high level of TMAO deteriorates chronic kidney disease. This article describes the relationship between TMAO and chronic kidney disease and the research progress of drugs targeted TMAO, providing a reference for the development of anti-chronic kidney disease drugs targeted TMAO. A persistently reduced glomerular filtration rate  based electrochemical sensor . These mAnaerococcus hydrogenalis, Clostridium asparagiforme, Clostridium hathewayi (. The majority (greater than 95%) of trimethylamine N-oxide was excreted in urine, only 4% of the dose was excreted in the feces and <1% in the breath (Trimethylamine N-oxide (TMAO) is a metabolite of choline, L-carnitine, and betaine in the diet. Choline and L-carnitine that are not absorbed in the small intestine are metabolized by the gut flora into trimethylamine (TMA) in the colon and then oxidized to TMAO in the liver by Flavin-containing monooxygenase 3 (FMO3) . The gutathewayi . The maje breath  , Sociodemographic factors , and lifestyle factor  . eGFR, aMetabolomic studies in CKD found TMAO is a potential biomarker that may help identify CKD patients . The TMAThe impaired renal TMAO clearance may lead to elevated circulating TMAO concentration and reduced glomerular filtration rate, which could aggravate burden of kidney . In anotHigh TMAO concentration is associated with long-term mortality in patients with CKD and coronary atherosclerosis . Higher Inflammation is an important mechanism for the TMAO-mediated occurrence and development of CKD. High concentration of TMAO leads to renal interstitial fibrosis and dysfunction by promoting renal oxidative stress and inflammation . SimilarThe mechanisms by which TMAO may enhance renal damage and aggravate nephropathy have not been well established. TMAO yet activates NF-κB signaling and then induce expression of inflammation gene . BesidesPrevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to Ruminococcaceae and Lachnospiraceae, as well as the Methane-producing bacteria Methanobrevibacter smithii  for 3 months, there was no change in TMAO level, but the betaine level in plasma was significantly increased  producing TMAO in the liver also need to be further explored . TherefoThere are four main enzymes involved in the production of TMA: choline-TMA lyase (CutC/D), carnitine monooxygenase (CntA/B), betaine reductase, and TMAO reductase . In addiNon-lethal targeting of microorganisms by selectively inhibiting pathways is beneficial to the host. TMA-production related enzymes such as CutC/D, CntA/B, and YeaW/X have become targets of current drug development . StudiesThere are many species of FMO3 substrate. Drugs such as Ranitidine, Benzydamine, Tamoxifen, Sulindac serve as substrates for FMOs . CurrentHowever, regulation of TMAO concentrations by targeting FMO3 remains unfavorable, because the accumulation of TMA will exhibit “Fish Malodor Disorder”, therefore, appropriate targets that regulate TMAO levels need to be investigated .K. pneumoniae was significantly decreased  elevated the level of phosphatidylcholine and decreased the level of TMAO (Fructus Ligustri Lucidi (FLL) reduced FMO3 expression and TMAO level by regulating the gut microbiota in elderly mice  attenuated TMAO-induced atherosclerosis (AS) by decreasing TMAO levels and increasing hepatic bile acid (BA) biosynthesis crobiota . Berbericrobiota . Gynoste of TMAO . TMAO is of TMAO . Fructusrly mice . Consistcrobiota . Nobiletcrobiota . Black Bcrobiota   treatment blunts the increase in circulating TMAO in mice on the choline-supplemented high-fat diet  and angiotensin receptor blockers (ARBs) are first-line drugs for chronic kidney disease treatment . Their mTMAO is closely related to chronic kidney disease. It is not only a risk factor for CKD but also a potential biomarker. This review summarizes the currently known drugs, natural compounds, probiotics, and prebiotics that can reduce the level of TMA and TMAO. Targeting the TMA-producing gut microbiota and TMAO-related enzymes are expected to be an important method to reduce TMAO level following the development of research on the gut microbiota and TMAO. It is unlikely that a single biomarker will satisfy the requirement of predicting CKD progression as it would be unlikely to reflect the complexities of the multiple pathophysiological processes involved in CKD progression. Therefore, TMAO may be used as a novel biomarker to assist other biomarkers to improve the accuracy of CKD detection.Firmicutes , its efficient adsorption function can attenuate absorption of hazardous metabolites in vivo. The use of AST-120 in animals and patients with chronic kidney disease can reduce oxidative stress and inflammation, and slow down the progression of kidney disease (In conclusion, there are many targets that regulate the production of TMAO. Nonlethal inhibition of the gut microbiota CutC/D, CntA/B et al. are of more clinical significance. Further research is needed to develop probiotics and probiotics to make them work  disease . There a disease , Thus se


Even with modern therapy, patients with heart failure only have a 50% five-year survival rate. To improve the development of new therapeutic strategies, preclinical models of disease are needed to properly emulate the human condition. Determining the most appropriate model represents the first key step for reliable and translatable experimental research. Rodent models of heart failure provide a strategic compromise between human in vivo similarity and the ability to perform a larger number of experiments and explore many therapeutic candidates. We herein review the currently available rodent models of heart failure, summarizing their physiopathological basis, the timeline of the development of ventricular failure, and their specific clinical features. In order to facilitate the future planning of investigations in the field of heart failure, a detailed overview of the advantages and possible drawbacks of each model is provided. Thanks to the advances in medical therapies for heart failure (HF), as well as the persistent improvements in cardiovascular surgical techniques and devices technologies, many previously fatal cardiac diseases are now chronically managed with satisfactory medium- and long-term prognosis. However, once the cardiac performance is severely affected, a progressively declining syndrome is established, whose definitive fate is often end-stage organ failure . DemograCurrent treatment options for end-stage HF entail organ replacement with human grafts, artificial devices, or xenografts. However, none these strategies are definitively curative (incorporating graft failure) and are limited by the availability of donors , chronicTo test novel putative therapeutic approaches to HF in a controlled manner, viable animal models of HF are paramount. Due to an advantageous compromise between adequate body size and low housing and maintenance costs, rodent models of HF have been extensively used by basic and translational scientists for decades ,20,21. PMany methods have been tested and validated to induce progressive HF and DCM in rats, mimicking the different etiologies of HF in humans. With the present review, we illustrate the available rat models of HF , highligRats and mice share the benefits of small mammalian models, in terms of ease of handling and housing, short breeding cycle, and the number of recruitable animals to improve the statistical power of experiments. The small physical size reduces the costs of novel therapeutic agents and molecules, whose administration is usually calculated based on body weight. However, some differences apply between these two species, starting with the size of the animals. Despite a similar 2–3 years life span, adult (6–8 week-old) rats weigh 250 to 550 g, while adult mice are generally 10 times smaller (25–30 g) . This asRodent cardiac physiology, contraction patterns, and energetics resemble the human equivalents. Rodent and human myocardial tissue share similar functions for many proteins, although rodent cardiomyocytes exhibit a predominance of alpha-myosin heavy chains (compared to beta-myosin heavy chains in humans), which are characterized by a rapid ATPase activity to facilitate the extremely high heart rate and the short cardiac cycle. Mice present a resting heart rate of 500 to 600 bpm, with 350 bpm for rats. Although still far from human values, the de-escalation from mice to rats in terms of cellular bioenergetics and mitochondrial efficiency contributes to translational value . These dThe mechanisms of HF are often multifactorial, involving several risk factors or acquired conditions that induce or accelerate myocardial damage, with or without a predisposing genetic background. Small animal models are particularly useful in the study of specific risk factors that promote HF, avoiding the confounding effects of external variables present in the clinical setting. Single pathophysiological pathways can be investigated: myocardial ischemia, pressure and volume overload, toxins, diabetes mellitus, atherosclerotic disease, and several metabolic syndromes ,26. In tThe high degree of genetic similarity between rodents and humans allowed for the creation of relevant transgenic and knockout strains with an HF phenotype . Easier The ideal animal model should be able to reproduce the typical echocardiographic, histological, and clinical features of the desired type of HF. Reflecting the higher prevalence of left-sided HF in the general population, left ventricular (LV) dysfunction models leading to HF and eventually DCM are more widely utilized. Human DCM is defined as a spectrum of myocardial diseases which share ventricular dilatation and depressed contractility . The keyIn DCM, associated diastolic dysfunction can occur, and the combination of increased LV filling pressures and ventricular dilatation often generates functional mitral regurgitation. Magnetic resonance imaging can detect areas of late gadolinium enhancement, which represent the process of diffuse fibrosis that is common to many DCM etiologies . Endomyocardial biopsy typically reveals morphological alterations in DCM: myocardial disarray, fibrosis, cell death, cardiomyocyte hypertrophy, scar formation, and inflammatory infiltration . ImportaTo date, a benchmark rat model of DCM is not available. Existing animal models are not able to respond to all of the above-mentioned requisites of the ideal model. The main reason lies in the fundamental difference in the development of human DCM versus the induction of experimental DCM. As previously stated, DCM in humans has a wide spectrum of causes, but in most of the cases a leading factor cannot be detected, often with evolution over significant time periods. Experimental DCM models rely mostly on a single pathogenic pathway with relatively rapid onset, which can consequently reproduce only some specific features of the DCM phenotype.Recently, scientific interest has moved towards other variants and causes of HF, generating the need for new, representative animal models. Heart failure with preserved ejection has been recognized as an independent clinical entity with specific etiologies and pathogenic pathways involved . Right vIschemic injury in rats has been induced in different ways: subcutaneous injections of isoproterenol , direct An alternative ischemic model consists of ligation of the circumflex artery, which is demonstrated to produce a significant infarct zone (40% of LV diameter) . HoweverA general concern regarding the ischemic rat model of HF is that the LAD ligation procedure is usually performed in young (4–8-week-old) rats, while ischemic diseases affect an older and multidiseased population. Since the regenerative potential of the human and mammalian heart is age dependent ,134, andWith the LAD or circumflex ligation models, it is clear that the subsequent impairment of myocardial performance will be limited to the LV. Although most of the reports using isoproterenol-induced HF describe changes in the LV, parallel hypertrophy in the RV has been observed, supporting a biventricular effect of this drug . ElectroDespite the mentioned limitations of the ischemic rodent model, it is indisputable that this model represents a primary reference platform for the study of ischemic HF. As an example of translational ability, ischemic injury models have permitted the study of the reverse remodeling properties of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists on LV volumes and performance , which nPressure overload can be generated in rats using surgical or non-surgical methods . SurgicaAortic banding can be achieved at different levels. In the original procedure described by Rockman et al. in a mouse model , a suturTightening of the aorta or PA can be accomplished using a suture tied against a needle, with the needle rapidly removed to restore antegrade blood flow. Given the need for complete vessel mobilization and the related risk of fatal bleedings, alternative techniques have been proposed, such as half-closed surgical clips , which gUsing these surgical approaches, delineated RV failure can be achieved 7 weeks from PA banding, as demonstrated by a reduced ejection fraction and cardiac output and severely dilated right chambers , with teAlthough technically challenging and with not insignificant mortality rates , rats caSurgical hypertensive models have been utilized to test reverse remodeling pharmacological strategies to treat HF, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists ,68,137 aNon-surgical hypertensive models of LV failure include angiotensin II infusion by osmotic minipumps implanted subcutaneously , Dahl saSeveral methods have been described to induce RV failure secondary to severe pulmonary hypertension , which have been extensively reviewed by Andersen et al. . InteresInjection of the vascular endothelial growth factor receptor (VEGFR) antagonist SU5416 (known as sugen), followed by a 2–3 week exposure to hypoxia, determines a paradoxical angio-obliterative pulmonary hypertension in rats, due to lung endothelial cell apoptosis . InterbrBoth extracardiac and intracardiac surgical methods have been described to induce volume overload in rats leading to HF . The extClosure of the aorto-caval fistula can be accomplished through a re-laparotomy using a hemoclip . AdoptinIntracardiac surgical methods include damaging the mitral, pulmonary, or aortic leaflets to generate acute valvular insufficiency and volume overload. The mitral valve is accessed through the LV apex, where a purse-string suture is placed and a 23G needle is advanced under echocardiographic guidance, puncturing the anterior mitral leaflet. After 2 weeks, a regurgitant fraction of 40% is reached, which determinates a progressive enlargement of the LV chamber  . A drop Aortic regurgitation is obtained by puncturing the valve with a fixed-core guidewire inserted from the surgically exposed right carotid artery . The temOnly one rat model of pulmonary regurgitation is currently available in the scientific literature. By lacerating the pulmonary leaflets with a 22.5 G needle inserted into the main PA through a purse-string suture, pulmonary regurgitation was achieved by Akazawa et al. . In thisFinally, multivalvular regurgitation involving all four cardiac valves has been produced by long-term pergolide and serotonin administration in rats , simulatDrug administration can induce HF in experimental rat models by direct toxicity of myocardial tissue , producing myocardial ischemia (isoproterenol), type 1 diabetes mellitus (streptozotocin ), or pulRepeated intraperitoneal doxorubicin injections represent one of the most validated rodent models of HF progressing to DCM . By geneWhile experimental papers focus mainly on doxorubicin’s effects on the LV, clinical experience in cancer survivors demonstrated that anthracycline treatment has a detrimental effect also on right-sided chambers . Recent Hyperhomocysteinemia in rats is achieved by specific amino acid-defined control diets. After 6 to 10 weeks of treatment, histopathological analysis reveals biventricular hypertrophy of cardiomyocytes, myocardial fiber disarrangement, perivascular and interstitial fibrosis, and inflammatory infiltrate ,109. In Acute intravenous administration of ethanol provokes myocardial dysfunction and hypotension, sustained by an abrupt increase in oxidative stress . ChronicSeveral rodent models of diabetes mellitus are available, recently reviewed by Pandey et al. . These mActivation of the inflammatory cascade in response to cardiac injury is a common mechanism of ventricular remodeling in many models of HF. After an insult, damaged cardiomyocytes release molecular signals that trigger an acute inflammatory response, digesting necrotic cell debris and promoting subsequent healing pathways . MonocytAcute autoimmune myocarditis has been reproduced in rats by injecting porcine myocardial myosin and generating a cross-reactivity with native cardiomyocytes. Using a two-stage protocol of subcutaneous footpad injection of purified porcine cardiac myosin supplemented with complete Freund adjuvant, cardiomyocyte injury, inflammatory infiltrate, and replacement fibrosis are achieved even 18 days after the completion of the injection protocol . ExtensiDue to practical reasons, rapid pacing-induced HF models usually involve larger mammals, in whom a pacemaker with a pacing lead in the RV apex is implanted subcutaneously and used to maintain supranormal heart rates for several weeks . Rapid pAlthough murine models of HF induced by specific genetic mutations are widely available, few genetically based rat models have been reported. Greaser et al. identified a rat strain with an autosomal dominant mutation of the gene encoding the RNA binding motif protein 20 (Rbm20), which alters the isoform expression of the sarcomeric protein titin (TTN) . Titin iGiven its central role in controlling the mechanical properties of the sarcomere, truncating variants of TTN lead to a wide number of inherited myopathies and cardiac disorders , rangingThe clinical phenotype of Duchenne muscular dystrophy includes the development of progressive DCM, the leading cause of death in this population . Using CIsca1, a causal gene for multiple mitochondrial dysfunction syndromes with cardiac dysplasia [Ling et al. developed a promising heterozygote knockout rat for the myocardium-specific ysplasia . From 3 ysplasia ,130.Recently, a novel rat model that relies on chemo–genetic interactions was established by Steinhorn et al., injecting rats with adeno-associated virus type 9 carrying a cardiac-specific recombinant D-amino acid oxidase, which produces hydrogen peroxidase during the conversion of D-amino acids into alpha-keto acids . When raLEDM2 gene in mice [Finally, several other genetic-based murine models of hereditary cardiomyopathy have been developed. Homozygous desmin knockout and knockin mice display the typical cardiac involvement  of autosomal-recessive desminopathies . Progres in mice . Manipul in mice . Previou in mice ,43,158.Adopting the most representative animal model provides the basis for reliable experimental research that translates to clinical practice. Rats provide a strategic compromise between sufficient body size for several morphological evaluations/ease of interventions and low maintenance costs/short breeding cycles. Understanding the advantages and possible drawbacks of each specific rat model can expedite experiments, improve reproducibility, and strengthen reliability. In the present review, we summarize the main characteristics of the currently available rat models of HF and describe their timelines for the development of ventricular failure and phenotypic features to facilitate the standardization and optimization of future investigations in the field of HF.


Ventricular arrhythmias are a common clinical manifestation in patients with cardiac sarcoidosis (CS) and other arrhythmogenic inflammatory cardiomyopathies (AIC). The management of sustained ventricular arrhythmias in these patients presents unique challenges. Current therapies include immunosuppressive, antiarrhythmic agents, and catheter ablation. Significant progress has been made in deciphering the importance of patient selection for ablation, systematic preablation evaluation, and optimal ablation timing, as well as ablation approaches and techniques. In this overview, we discuss the evaluation and management of ventricular arrhythmias in patients with CS, focusing on catheter ablation, which has evolved into an effective approach in reducing the burden of ventricular arrhythmias in these patients in the context of multifaceted treatment along with medical therapies. Arrhythmogenic inflammatory cardiomyopathies (AICs) are nonischemic cardiomyopathies that can result in ventricular arrhythmias due to myocardial inflammation . AICs arSarcoidosis is the most common of the AICs and represents a systemic inflammatory disorder due to an exaggerated immune response to unidentified antigens resulting in the formation of noncaseating granulomas and fibrosis . CardiacCS can affect any of the heart layers: endocardium, myocardium, and/or epicardium. Cardiac involvement is usually multifocal with progression from active inflammation to fibrosis and scarring. The most commonly affected chamber is the left ventricle (LV) at the interventricular septum. CS has a predilection to the basal septum, lateral mitral annulus, and LV summit . The rigThe mechanisms of ventricular arrhythmias in CS include abnormal automaticity, triggered activity, and reentry  8]. Are. Are8]. The diagnosis of CS can be challenging due to the overlap of symptoms with other cardiac AICs. Furthermore, CS is characterized by patchy disease distribution, which makes the diagnosis of CS difficult depending on the location and extent of cardiac involvement. A diagnosis of definite CS can be made by endomyocardial biopsy, which is particularly useful in patients with suspected isolated CS. However, the yield of endomyocardial biopsy is low, with a reported sensitivity in the 20–30% range . The dia18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), has been increasingly used in patients with suspected CS. On CMR imaging, late gadolinium enhancement (LGE) indicates inflammation or fibrosis/scar. The most common patterns of LGE in CS include subepicardial and mid-myocardial LGE along the basal septum and/or inferolateral wall [Advanced cardiac imaging, including cardiac magnetic resonance (CMR) imaging and cardiac ral wall . In a meral wall . Recent ral wall .18F-FDG-PET imaging for the diagnosis of CS, FDG-PET scan imaging had a sensitivity of 89% and a specificity of 78% for the detection of CS [Focal FDG uptake on cardiac PET imaging indicates disease activity in granulomatous myocarditis. In a meta-analysis including seven studies evaluating the accuracy of on of CS . FDG-PETDSP) mutations, which can be found in around 50% of patients with ARVC, as well as acute and chronic myocarditis, and other familial dilated cardiomyopathies [In recent years, the expanding use of metabolic activity FDG cardiac PET imaging and genetic testing in patients with ventricular arrhythmias has led to increased recognition of nonsarcoid, inherited cardiomyopathies presenting as AICs . Traditiopathies ,22. ThesThe primary treatment of CS with active inflammation is immunosuppression with corticosteroids. A typical regimen includes prednisone 30–40 mg daily for 4–8 weeks, followed by a taper by 5–10 mg every 2–4 weeks until reaching a maintenance dose of 5–15 mg daily. The maintenance dose is then continued for 9–12 months. Small series have also reported the effectiveness of intravenous methylprednisolone 40 mg once or twice daily for 3 to 5 days to control VT storm in patients with CS in addition to antiarrhythmic drug therapy . MonitorSteroid-sparing immunosuppressant agents such as methotrexate, leflunomide, mycophenolate mofetil, hydroxychloroquine, and azathioprine were previously considered second-line in the treatment of CS. However, most centers now initiate these agents early in the course of treatment in conjunction with corticosteroids in patients requiring long-term immunosuppression to reduce the side effects of corticosteroids . The tumPadala and colleagues showed that early initiation of corticosteroids in CS was beneficial in preventing recurrence of ventricular arrhythmias as compared to delayed initiation of corticosteroids or failure to use corticosteroids . YodogawThere are limited data regarding the outcomes of antiarrhythmic medications in patients with CS. Class III antiarrhythmic agents, such as sotalol and amiodarone, are most commonly used in these patients. Amiodarone should be avoided in patients with advanced lung and/or liver disease due to sarcoid involvement, though it may be the only effective antiarrhythmic drug option in refractory arrhythmia cases. Class IC antiarrhythmic agents should generally be avoided in CS similarly to other structural heart diseases.Based on the 2017 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) guidelines for management of patients with ventricular arrhythmias and prevention of sudden cardiac death, indications for implantable cardioverter defibrillator (ICD) implantation in patients with CS include: sustained VT or cardiac arrest (class I), LV dysfunction with an LVEF ≤ 35% (class I), or an LVEF > 35% with syncope, scar on CMR or PET scan, inducible ventricular arrhythmias, or indication for permanent pacing (class II a) . ApproprEven with the use of immunosuppressive and antiarrhythmic medications, patients with inflammatory cardiomyopathy are still at increased risk for VT, which can lead to sudden cardiac death or ICD shocks. As such, CA is an important treatment modality for patients with PVCs and VT, especially when arrhythmias are refractory to medical therapy ,34.Mechanisms for ventricular arrhythmias in CS can be broadly related to ongoing myocardial damage during the active phase, and fibrotic replacement of normal tissue and cardiac chamber remodeling facilitating reentrant circuits ,34,35. IUnlike ischemic cardiomyopathy, the arrhythmogenic substrate in AICs does not follow a coronary distribution . The epip = 0.013), with most patients exhibiting mid-myocardial (32%) or subepicardial (39%) LGE. Of note, 95% of patients were noted to have basal involvement. On electroanatomic mapping, bipolar  and unipolar  low-voltage abnormalities (LVAs) were recorded in both ventricles and the epicardium. A comparative analysis of imaging and electroanatomic mapping findings showed the best agreement between CMR imaging and endocardial unipolar mapping  as well as CMR imaging and epicardial bipolar mapping  [n = 64, 73%) was the most common although multifocal findings were also frequent . Additionally, 31 (35%) and 19 (22%) had mid-myocardial and epicardial LGE, respectively [Efforts have been undertaken to elucidate the arrhythmogenic substrate in greater detail specifically in CS patients. Among 21 patients who underwent electroanatomic mapping at the time of VT ablation procedures, there was extensive scarring in both the RV (16/18) and LV 14/15) as well as the epicardium (7/8). The pattern of scarring in the RV appeared more confluent and evenly distributed across regions; by contrast, LV scarring was patchy and favored the septum, anterior wall, and outflow tract / aortomitral continuity [/15 as we< 0.001) . In the ectively . It shouectively . RV invoectively . Overall18FDG PET/CT and CMR imaging have emerged as powerful and complementary tools in the assessment of AICs, especially CS [Multimodality cardiovascular imaging techniques have become quintessential in the treatment of patients with suspected or confirmed AIC . The utiially CS ,49,50. Iially CS ,42. Convially CS ,48,50. Nially CS ,41,42. Fially CS .Current data regarding VT ablation outcomes in nonsarcoid AICs are limited to observational studies. Although incompletely understood, the underlying etiology likely informs the approach and outcomes for VT ablation. In a series of 20 patients with biopsy-proven viral myocarditis and refractory VT, endocardial ablation was acutely successful in 14 (70%), whereas the other 6 (30%) underwent epicardial ablation 2–27 days (median 10 days) following the prior endocardial procedure; 18/20 (90%) were free of sustained VT over a median follow-up time of 28 months . Combinen = 158), the 1- and 2-year cumulative incidences of VT post-ablation were 37% and 44%, respectively [CA of ventricular arrhythmias in CS has been a topic of great interest in the past 1–2 decades . The repectively . HoweverPatients with inflammatory cardiomyopathy are at risk of malignant ventricular arrhythmias, notably VT/VF storm (defined as ≥3 sustained episodes within a 24 h period) and incessant VT  ,36,57. CVentricular arrhythmias in the setting of AICs, most often CS in clinical practice, represent unique management challenges requiring a multifaceted approach with both medical and ablative interventions. CA is an effective treatment modality in conjunction with antiarrhythmic drugs and immunosuppressive agents. Outcomes of CA are superior when performed earlier in the disease course before LV function has been compromised and when performed in the absence of active myocardial inflammation.The diagnostic evaluation of patients with suspected cardiac sarcoidosis requires a thorough assessment for exclusion of mimicking conditions that may also present with inflammation by FDG-PET scan.Catheter ablation is an effective strategy for patients with inflammatory cardiomyopathy and ventricular arrhythmias  that are refractory to immunosuppression and antiarrhythmic drugs.18FDG PET/CT and/or CMR imaging can be helpful in assessing the presence of inflammation and characterizing the involved substrate.Preprocedural cardiovascular imaging with When possible, catheter ablation should be deferred until active inflammation has been suppressed.


P < 0.05). The left ventricular ejection fraction of these 5 patients increased by more than 15%. CRT significantly improved the left ventricular structure and function of these 5 patients. During the 1-, 3-, 6-, and 12-month follow-ups, no left ventricular lead dislocations were observed. This loop technique is safe and effective and can be considered for repeated intraoperative dislocation during transvenous left ventricular lead implantation through the coronary sinus of a CRT device.Cardiac resynchronization therapy (CRT) for heart failure requires transvenous insertion of a left ventricular pacing lead through the coronary sinus. However, repeated intraoperative dislocations often occur. Therefore, we describe a novel technique that uses the loop technique to treat patients with repeated intraoperative dislocations during transvenous left ventricular lead implantation to stabilize the lead in its final position. In five patients with repeated intraoperative dislocation during transvenous left ventricular lead implantation, the loop technique was successfully used to stabilize the lead in its final position. The pacing and sensing parameters were satisfactory in all patients at implantation and 12 months post-operatively. Compared with the pre-operative values, the 12-month post-operative values for the left ventricular ejection fraction were significantly increased and the left ventricular end systolic dimension and left ventricular end diastolic dimension were significantly decreased ( The prevalence of heart failure is gradually increasing, and it has a high mortality rate . The treinterventricular, and atrioventricular contractions –6. The fIn this study, we describe a novel and effective technique using the loop technique for repeated intraoperative dislocations during transvenous left ventricular lead implantation of a CRT device.Between December 2017 and March 2020, patients with advanced heart failure and widened QRS complex received CRT. All symptomatic patients had left ventricular ejection fraction ≤35% in NYHA Class III or IV with a prolonged QRS duration > 130 ms despite optimal medical therapy. CRT implantation criteria met the guidelines . All patPatients were under local anesthesia and conscious sedation during the operation. The left subclavian vein was used to introduce separate guidewires for the right atrial, right ventricular, and left ventricular leads. A balloon occlusive venogram was performed after coronary sinus cannulation in every patient to select the target vein . Whenever repeated left ventricular lead dislocations (≥2 dislocations) were encountered, by protocol at least one other lead configuration  was tried. Finally, an attempt was made to position the left ventricular lead by using the loop technique according to the protocol.The loop technique procedure for the left ventricular lead was achieved in the following stepwise manner : (1) theIf acceptable parameters were obtained in repeated measurements, the guidewire was removed, and the lead was sutured. The position of the left ventricular lead in the RAO 30° and LAO 60° projections was recorded. Finally, the subcutaneous tissue was adjusted, and the skin was closed.Follow-up parameters were measured pre-discharge and 1, 3, 6, and 12 months post-implantation. In addition, at the 12-month follow-up, chest X-ray images were repeated in the same projection to verify the left ventricular lead position.t test. A P value of <0.05 was considered statistically significant.All statistical analyses were performed with SPSS version 20 . Continuous variables were presented as the mean ± SD, and the pre-operative and post-operative differences were compared using Student’s In the 64 consecutive patients selected for CRT, 5 patients (7.81%) had repeated intraoperative left ventricular lead dislocation, including 2 males and 3 females with a mean age of 60 years old (from 55 to 65 years old). Four patients were diagnosed with dilated cardiomyopathy, and 1 patient was diagnosed with coronary heart disease . The preThe left ventricular leads used for this technique included ST. JUDE medical 1458 (4 patients) and Medtronic 4195 (1 patient). At implantation, the threshold, impedance, and R wave of the left ventricular lead were 1.48 ± 0.18 V, 812.6 ± 95.7 ohms, and 11.6 ± 1.8 mV, respectively. At 12 months post-operation, the threshold, impedance, and R wave of the left ventricular lead were 1.15 ± 0.23 V, 850.6 ± 174.4 ohms, and 10.7 ± 0.7 mV, respectively. The pacing and sensing parameters were satisfactory in all patients at implantation and 12 months post-operatively .P < 0.05). The LVEF of those 5 patients increased by more than 15%. Therefore, CRT significantly improved the left ventricular structure and function of these 5 patients.At hospital pre-discharge and at the 1-, 3-, 6-, and 12-month follow-ups, no patient had died, there were no CRT infections, and no lead dislocation were observed. Cardiac resynchronization therapy has become a valuable non-drug treatment for refractory symptomatic heart failure, severe left ventricular systolic dysfunction, and ventricular dyssynchrony in patients with inadequate response to optimal medical therapies . CRT hasThe loop technique used in this study provides a safe and effective solution for patients with repeated intraoperative left ventricular lead dislocation. In five patients with repeated intraoperative dislocation during transvenous left ventricular lead implantation, this loop technique was successfully used to stabilize the lead in its final position. In order to facilitate the formation of the loop and fix lead, long lateral/posterolateral vein and a reasonable amount of backup by a guiding catheter were needed. Intra-operative and post-operative pacing and sensing parameters at the 12-month follow-up were satisfactory in all patients. During the 12-month follow-up, no patient had died, there were no CRT infections, and no lead dislocations were observed. CRT improved the left ventricular structure and function, the functional status, and the hemodynamic status.via interventricular septal puncture may also be effective and durable, with significant but potentially acceptable risks in a cohort of 15 patients , surgery can be considered and direct surgical epicardial left ventricular lead placement may provide the potential to pace the optimal target site. Although both the median sternotomy and left thoracotomy are available, minimally invasive approaches reduces the risk of surgery and the incidence of complications. Ceresa et al. reported their experience with CRT through a left minithoracotomy after failed transvenous approach . The MyoIn recent years, improvements in left ventricular leads and delivery systems have made CRT more accessible to patients with heart failure. In clinical practice, the standard first-line approach is the transvenous epicardial left ventricular lead placement through coronary sinus. The surgical access is most frequently used as a second choice. At present, there is a lack of data on the safety and effectiveness of some new techniques, but these methods may provide an alternative to left ventricular lead dislocations.However, it must be acknowledged that there are some limitations to our findings. Although no adverse outcomes of the lead were observed during the short-term follow-up, it is necessary to extend the follow-up time. This loop technique was used in only 5 patients in this article. Therefore, additional studies with more patients are needed to explore the clinical value of this technique. However, we believe that until these results are available, this loop technique can be used as a means for repetitive left ventricular lead intraoperative dislocation through the coronary sinus if the standard implantation procedure fails.In summary, this is the first report that shows the feasibility of repetitive intraoperative dislocation of the left ventricular lead through the coronary sinus using the loop technique. We have demonstrated that this loop technique is safe and effective, and it can be considered for repeated intraoperative dislocation during transvenous left ventricular lead implantation through the coronary sinus of a CRT device.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Medical Ethical Review Board of Shaanxi Provincial People’s Hospital. The patients/participants provided their written informed consent to participate in this study.All authors contributed to the patient care, diagnosis, treatment, and the writing of this manuscript 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.