Copeptin is the carboxyl-terminus of the arginine vasopressin (AVP) precursor peptide. The main physiological functions of AVP are fluid and osmotic balance, cardiovascular homeostasis, and regulation of endocrine stress response. Copeptin, which is released in an equimolar mode with AVP from the neurohypophysis, has emerged as a stable and simple-to-measure surrogate marker of AVP and has displayed enormous potential in clinical practice. Cardiovascular disease (CVD) is currently recognized as a primary threat to the health of the population worldwide, and thus, rapid and effective approaches to identify individuals that are at high risk of, or have already developed CVD are required. Copeptin is a diagnostic and prognostic biomarker in CVD, including the rapid rule-out of acute myocardial infarction (AMI), mortality prediction in heart failure (HF), and stroke. This review summarizes and discusses the value of copeptin in the diagnosis, discrimination, and prognosis of CVD , as well as the caveats and prospects for the application of this potential biomarker. Cardiovascular disease (CVD) is currently acknowledged as a primary threat to the health of the global population. According to the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, CVDs are attributed to the largest number of deaths among non-communicable diseases, with an estimated 17.8 million  deaths, accounting for approximately one-third of all deaths globally , elevateArginine vasopressin (AVP) is a crucial hormone that regulates fluid homeostasis, vasoconstriction, and endocrine stress response. As the C-terminal fragment of the pro-AVP precursor, copeptin is released in an equimolar amount with AVP in response to osmotic, hemodynamic, and stress stimuli , 8. CopeCopeptin, a leucine-rich glycopeptide (molecular mass ~4 kDa), was first discovered by Holwerda from the posterior pituitary of pigs , and itsPre-pro-vasopressin is synthesized in the magnocellular neurons of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. The axons of these neurons constitute the hypothalamic-pituitary tract, which terminates in the posterior pituitary. During transport along the tract, the precursor is proteolytically cleaved into AVP, neurophysin II, and copeptin, and the products are stored in the posterior pituitary –23. The After release into the bloodstream, AVP activates intracellular effectors by binding to three receptor subtypes  , 28. V1a2O) caused similar release kinetics of plasma copeptin (from 4 to 29.3 pmol/L) and AVP (from 1 to 10.3 pg/ml). They also reported that copeptin and AVP concentrations were highly correlated, with a Spearman rank correlation coefficient of 0.94. Non-specific somatic stress is another factor that regulates copeptin. Copeptin levels are significantly higher in patients with acute diseases, such as sepsis  in a healthy cohort of 359 individuals . Median AVP has several detection limitations, including a short half-life, instability in circulation, and association with platelets, and the radioimmunoassay is not readily available in routine check-ups , 12, 51.As a common cardiac emergency, AMI caused by myocardial ischemia and necrosis has a high risk of morbidity and mortality if not treated timeously . TherefoCardiac troponins (cTn) are a group of cardiac structural proteins that regulate the calcium-mediated interaction of actin and myosin . When a Unlike cTn and other cardiac biomarkers, copeptin, which non-specifically reflects the endogenous stress level at the onset of AMI, has been advanced and widely validated for its clinical value in AMI.As a marker of endogenous stress, copeptin levels rise sharply after myocardial injury following a swift decline , 66. A mThe release pattern of copeptin in 145 patients undergoing percutaneous coronary intervention (PCI) for a first STEMI was reported by Gu et al. , who repFor patients with AMI, the somatic stress burden is high, and the vasopressin system is activated . CopeptiGiven the different temporal release patterns of copeptin, when it is used in combination with the time-dependent cardiac marker cTn , copeptin has the potential to allow for rapid and accurate rule-out of AMI. This hypothesis was first proposed by Reichlin et al.  in 2009 Although the combination of copeptin with conventional cTn provided significant benefits, the incremental value of copeptin when used with hs-cTn compared with hs-cTn alone remains unclear and inconsistent for an instant the rule-out of NSTEMI , 91–93. When the hs-cTn assay is available and well validated, patients with “very low” or limit of detection (LOD) level of hs-cTn  on admission (0 h) could be eligible for “rule-out” and may be discharged if the ECG and/or clinical symptoms suggest a low risk of ACS . In ordeA secondary analysis  from a mHowever, some studies have concluded that this dual marker strategy (combination of copeptin and hs-cTn) might provide higher eligibility or efficacy  to rule out NSTEMI , 103. GiThe diagnostic performance of copeptin in different subgroups of the population was investigated further. A study on sex-based differences of copeptin combined with cTn for early rule-out of NSTEMI reported that men had a similar NPV (100%) as women [99.6% (95% CI 98.8–100%)] . AnotherPoint-of-care testing (POCT) assays for cTn are important detection tools when commercial cTn or hs-cTn assays in laboratory platforms are unavailable, but the analytical sensitivity of POCT assays cannot fulfill this requirement. Vafaie et al.  found thOf note, there are several caveats and cautions when using copeptin to rapidly identify AMI. First, as a relatively novel biomarker, the optimal cut-off value of copeptin should be carefully investigated to reach a consensus, as assays for both copeptin and cTn have been improved to an increased sensitivity level. Many studies adopted a copeptin cut-off of 14 pmol/L , 83, 95,Second, it is essential to realize that negative copeptin results do not indicate the absence of coronary artery disease, because the extent of copeptin release triggered by ischemia (such as unstable angina) was weaker than other acute stimuli, such as AMI , 67, andThird, as a non-specific biomarker, copeptin can be significantly elevated in many fluid disorders and stress-associated diseases –153. EleThere are different subtypes of myocardial infarction (MI), the most frequent are type 1 MI (T1MI) (caused by atherothrombotic coronary artery disease) and type 2 MI (T2MI) (associated with a mismatch between oxygen supply and demand) . The difp = 0.0016]. The difference between the two studies may be attributed to the adjudication of the final diagnosis: the former is based on cTnI and the latter is based on hs-cTnI, and a higher percentage of minor T2MIs might be identified with hs-cTnI.In 2020, a retrospective study  analyzedPrompt assessment and identification of patients with AMI who are at risk of adverse outcomes are necessary for optimized care and resource allocation. Therefore, prognostic markers for predicting the mortality rate and adverse outcomes of MI are extensively favored. Nowadays, serial measurement of hs-cTn, as well as B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration have been recommended for the assessment of prognosis , 160. ElSeveral studies have indicated that copeptin is a useful prognostic predictor for adverse outcomes in patients with ACS , 161–164p = 0.002)  during long-term follow-up (median 30.1 months) in the participants (OR = 1.6) . For pat= 0.002) . Another= 0.002) .Heart failure (HF), resulting from an abnormality in cardiac structure or function, is one of the most common causes of hospitalization and mortality worldwide . HF is dHF can be classified into two categories based on systolic function: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). HFrEF is defined as a clinical diagnosis of HF and left ventricular ejection fraction (LVEF) < 40%, whereas HFpEF refers to those with LVEF ≥ 50% . PatientThe clinical syndromes and signs of HF are non-specific; therefore, careful history taking and physical examination are pivotal in the assessment of HF , 181. CuOwing to a relatively well-established knowledge, the current treatment of HF is mainly targeted at the neurohormonal systems with a predominance of a blockade of adrenergic receptors and the renin-angiotensin-aldosterone system, such as angiotensin-converting enzyme inhibitors, beta-blockers, and angiotensin-II receptor antagonists . OveractPatients with HF suffer greatly from water retention and volume overload, which is assumed to be attributed to the inappropriate activation of the vasopressin system. In addition, a non-osmotic pathway is also believed to regulate AVP release through intra-cardiac pressures, intra-arterial pressures, angiotensin II, pain, and adrenergic central nervous stimuli , 188. SiThe performance of copeptin as a surrogate marker of AVP in risk stratification of patients with HF has been proposed and widely evaluated. Xu et al. found  that copCurrently, copeptin has also been demonstrated to be a relatively good predictor of mortality in patients presenting to the ED with acute dyspnea , 199. A In addition, for patients with HF, copeptin has been proposed as a potential predictor of outcome or mortality. Copeptin was reported to be associated with left ventricular dysfunction, volumes, remodeling, and clinical HF post-AMI, indicating that copeptin measurement might add up prognostic information . The firFor patients with acute HF, a multicenter trial reported significantly increased the 90-day mortality, readmissions, and ED visits in patients with elevated copeptin levels, especially in those with hyponatremia (HR = 7.36) . AnotherFurthermore, the combination of copeptin with other biomarkers (such as hs-cTnT and NT-proBNP) might improve the prognostic performance of patients with HF compared to a single marker , 127. InHowever, contradictory results that copeptin alone or in combination with other conventional biomarkers has limited clinical value cannot be ignored , 204. FoIn addition, it remains unclear whether copeptin can be used to monitor and guide medical therapy for patients with HF, and whether there exists a single cut-off level of copeptin for physicians to decide healthcare allocation in HF. Studies have investigated whether NT-proBNP and copeptin levels have the ability to optimize beta-blocker (BB) up-titration in patients with HF, but they came to inconsistent conclusions in terms of the performance of copeptin , 206, inStroke is the second leading cause of CVD burden, resulting in over 6 million deaths in 2013 . Stroke Stroke conditions serve as acute stressors, activating the HPA axis, which regulates the release of CRH from the hypothalamus. CRH stimulates the release of ACTH from the anterior pituitary. Another stimulated hypothalamic hormone is AVP, which can interact with CRH and lead to the secretion of ACTH . It has IS is associated with detrimental and fatal conditions and contributed to 62.4% of all stroke incident cases in 2019 . Early rRecurrent vascular events after TIA and IS should be carefully monitored and predicted. Greisenegger et al.  investigICH is the second most common cause of stroke after IS, but ICH accounts for more disability and mortality and a greater economic burden worldwide , 227. InCopeptin was elevated in patients with cerebral infarction (CI), ICH, and SAH compared to healthy controls, but it could not discriminate CI, ICH, and SAH from each other . In addiProvided that copeptin is secreted in equimolar amounts with AVP and correlates well with AVP release, it can serve as a promising and reliable surrogate of AVP, which is difficult to measure. Copeptin measurements have been shown to play essential roles in harmful CVDs. Copeptin has been reported to be an excellent tool for AMI rapid rule-out when combined with cTn evaluation in patients with potential AMI, as well as for risk stratification and outcome prediction in patients with AMI, HF, and stroke. However, additional larger, well-designed trials are still required to assess the incremental value of copeptin when added to conventional diagnostic or prognostic models of CVD and to evaluate the clinical benefits and applicability of copeptin measurement in routine practice and patient care. Whether copeptin can serve as a treatment indicator in therapies targeting the vasopressin system should be further explored and validated.DM wrote the first draft of the manuscript and prepared the figures. JC prepared the tables. XC and LQ conducted review of the manuscript. All authors contributed to the final revision of the 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.


Cardiac amyloidosis (CA), a significant condition resulting in infiltrative cardiomyopathy and heart failure with preserved ejection fraction (HFpEF), is caused by extracellular deposition of amyloid fibrils in the heart. Even though this has been known for an extended period, its prevalence in elderly patients with heart failure is increasingly being recognized. Recent advances in diagnosis with non-invasive methods like technetium pyrophosphate-labeled cardiac scintigraphy  and treatment options with tafamidis have played a pivotal role in awareness of the burden of this disease. Management of cardiac complications like heart failure, atrial arrhythmias, conduction block, ventricular arrhythmias, coronary artery disease, and aortic stenosis is now more critical than ever. We aim to review and outline the recent advances in diagnoses of CA. We also review management strategies for cardiac complications of CA with a brief summary of disease-modifying therapies. ATTR amyloidosis may result from a genetic mutation in the TTR gene, which is inherited (ATTRv), or may result from age-related deposition from wild-type ATTR (ATTRwt).–CA should be suspected in elderly patients with heart failure symptoms such as dyspnea or fatigue. Deposition of amyloid fibrils in the atrium and the conduction system, including the atrioventricular (AV) node, may result in various rhythm abnormalities. These range from atrial tachycardias such as atrial fibrillation to AV conduction delays to heart blocks. In recent studies on the autopsied heart, amyloid deposition in the ventricles is found frequently; however, sustained ventricular tachycardias are not frequently reported. Although many organ systems are typically involved, cardiac involvement is the leading cause of mortality and morbidity in 50-70% of cases. Diagnosis is achieved by detecting free light chains or monoclonal immunoglobulins in blood and urine. Treatment is through specifically directed chemotherapy.Plasma cells produce monoclonal immunoglobulin light chains, which result in amyloid fibrils responsible for AL amyloidosis. Cardiac involvement in AL amyloidosis is attributed to two mechanisms. One is the extracellular deposition of amyloid fibril in the myocardium, and another involves direct cardiotoxicity from the fibril aggregates. However, with the recent recognition of the disease and the development of noninvasive diagnostic modalities, ATTRv amyloidosis has also been implicated in causing cardiomyopathy. Despite these advances, there remains a vast number of undiagnosed cases of ATTR amyloidosis. Studies on valves replaced/removed by either transcutaneous or surgical approach have shown a 16-25% prevalence of ATTRwt deposits. This has led to an increased focus on CA in pre-operative evaluation for transcatheter aortic valve replacement (TAVR).Previously, ATTRv amyloidosis was considered to be of neurological importance and ATTRwt to be of systemic importance. This was because of the predominance of neurological symptoms, including neuropathies reported with ATTRv amyloidosis. ATTRwt amyloidosis was always known to be a culprit for cardiomyopathy.In the absence of effective therapies for cardiac amyloidosis previously, diagnosis of AL and ATTR amyloidosis was not an area of focus. However, with the advent and availability of specific chemotherapy, early diagnosis and initiation of therapy are crucial. ATTRwt amyloidosis may concern patients with bilateral carpal tunnel syndrome and lumbar stenosis, as such manifestations may predate cardiomyopathy by decades.Clinical clues are essential in leading clinicians toward thinking of amyloidosis. AL amyloidosis is associated with multisystem involvement. Thus, signs of nausea, vomiting, diarrhea, gastrointestinal bleeding for GI involvement, renal failure with albuminuria, and systemic symptoms of macroglossia are typical red flag symptoms. ATTRv amyloidosis may present with early neurological symptoms of neuropathies which may be diffuse or axonal. Atrial deposits can result in arrhythmias, and deposits in the conduction system resulting in heart block may represent other findings on the electrocardiogram. Pseuodoinfaction identified by pathological Q waves or QS waves on two consecutive leads is seen in patients with AL amyloidosis. If present, the study demonstrates worse outcomes of AL amyloidosis.Electrocardiography is typically the first diagnostic study to be performed due to its easy availability. Low voltage QRS complexes have been known to be associated with cardiac amyloidosis, although recent data suggests it may be over-implicated. Almost 70% of patients with proven cardiac amyloidosis may not have low voltage and may have a standard or even high voltage meeting the criteria for left ventricular hypertrophy. LVEF has been previously used to diagnose and monitor patients with decline associated with disease progression. It is noted that LVEF declines later, and thus, it does not accurately predict the worsening of the disease. Global longitudinal strain (GLS) has developed as an emerging tool to predict diagnosis and outcome accurately. Relative apical sparing of GLS resulting in a bull’s eye pattern of apical sparing is strongly suggestive of CA, differentiating from other causes of cardiomyopathy. GLS has proved to be superior to LVEF in diagnosis, risk stratification, and decision-making amongst patients with AL amyloidosis.Echocardiography has been an essential tool for the evaluation of patients with symptoms of heart failure. Unexplained LV thickness >12 mm, along with grade 2 or worse diastolic dysfunction and reduced tissue doppler velocity, can meet echocardiographic criteria; however, these need to be coupled with biopsy or nuclear imaging. Recent studies challenge the typical LGE pattern in CA of global subendocardial enhancement. Progression of LGE pattern from subendocardial to transmural has been recently reported. CMR was also studied for its ability to differentiate between AL and ATTR amyloidosis; however, it was not found to be sensitive or specific.Cardiac magnetic resonance (CMR) utilizes its intrinsic property to differentiate normal myocardium from pathologic through T1 and T2 signals. This, when coupled with late gadolinium enhancement (LGE) and extracellular volume (ECV) measurement, vastly improves the diagnostic ability for CA. 99mTc-hydroxydiphosphonate (HMDP) and 99mTc-DPD are other radiotracers used in Europe, depending on availability. Heart to contralateral lung ratio (H/CL) evaluated 1 hour after uptake quantifies cardiac uptake. Visual uptake is reported by the Perugini grading system, with grade 0 reported with no cardiac uptake, grade 1 reported with mild cardiac uptake compared to rib, grade 2 with equal uptake, and grade 3 with higher cardiac uptake compared to rib. While studies have shown that grade 2 and 3 uptake and H/CL ratio >1.5 are sensitive for ATTR amyloidosis, mild uptakes are also noted in about 40% of cases with AL amyloidosis. Recently, the H/CL ratio has been challenged. Mitral annular and aortic valve calcifications can cause increased uptake while myocardial scars can cause decreased uptake. Blood-blood imaging (PYP in blood pool in RV and LV cavity) can cause false positives. Therefore SPECT evidence for PYP uptake is considered a diagnostic cornerstone.Nuclear imaging with bone scintigraphy and single photon emission computed tomography (SPECT) is widely available. 99m Technetium-pyrophosphate (PYP) is increasingly used to diagnose ATTR amyloidosis in the United States. It is also now recognized as confirmatory in the absence of cardiac biopsy. With the availability of such a test, obtaining a PYP scan in patients with LV thickness ≥12 mm on echocardiogram and any one red flag sign is recommended. We utilize the algorithm as noted inGiven AL amyloidosis's different management and prognosis, it is important to rule it out with the help of urine and blood immunoglobulin light chains. Once AL amyloidosis is ruled out, grades 2 and 3 uptake become more than 90% sensitive and 98% specific for ATTR CA when coupled with positive SPECT images. However, studies with a direct comparison between SPECT and PET have demonstrated the superiority of SPECT over PET in terms of sensitivity and specificity for the diagnosis of ATTR CA.Position emission tomography (PET) has been studied and suggested to have a role in diagnosis and therapeutic monitoring. Beta-blockers can also precipitate hypotension by decreasing heart rate and contractility; however, a recent study from Italy has demonstrated that beta-blockers may be tolerated for the management of co-morbidities even in the presence of CA., Calcium channel blockers are implicated in binding to amyloid fibrils which may result in cytotoxicity. If treated with digoxin, CA is already prone to arrhythmias due to amyloid deposition in the atrium, which can increase fatal arrhythmias. Treatment should be diuretics which help relieve congestion as needed. Loop diuretics have been used for an extended period in CA; however, recent data suggest vasopressin receptor antagonists may be more suitable for achieving balanced euvolemia and avoiding the risk of hypotension with loop diuretics. In addition, recent emperor preserved and deliver trials have shown the benefit of sodium-glucose cotransporter 2 inhibitors in patients with HFpEF in decreasing hospitalizations and are now incorporated in HFpEF management with 2a evidence. Although specific studies on patients with CA are lacking, data from these trials can be extrapolated in this specific circumstance.,Treatment of cardiac amyloidosis focuses on managing cardiac complications and preventing the worsening of underlying organ failure. The most common complication encountered clinically is heart failure. Typically, it presents as HFpEF. Management strategies with usual heart failure medications may prove harmful in CA. ACE inhibitors/ARBs may aggravate orthostatic hypotension secondary to activation of the renin-angiotensin-aldosterone system due to autonomic dysfunction. A similar value holds for catheter ablations, with a recent study demonstrating an 80% recurrence rate at two years. Anticoagulation with NOACs is indicated irrespective of the CHA2DS2-VASc score because of the risk of thrombus formation in CA due to its inherent risk of thrombogenicity beyond known risk factors.Atrial fibrillation is a known complication of CA; however, its management has been of interest recently. Rate control medications such as beta-blockers and calcium channel blockers are relatively contraindicated, as noted above. Rhythm control strategies may be appropriate, and amiodarone is the antiarrhythmic drug of choice. Electrical cardioversion is also attempted; however, it is essential to rule out LA thrombus, and the recurrence rate of atrial fibrillation is high at 51%, as noted in a recent study. ATTR CA has a better prognosis than AL amyloidosis; however, that as well is about 3-5 years. A decision that will need to be addressed in this scenario is whether the short-term risk of CABG outweighs its long-term benefits, given prognosis is not prolonged to reap the benefits of CABG. Heart block is a known complication of CABG, and the risk may be very high in patients with CA. Case reports have shown increased morbidity in patients with CA undergoing CABG. Further studies looking specifically at the question of PCI versus CABG in patients with CA and triple vessel CAD are needed.Coronary artery disease (CAD) in patients with CA presents various issues regarding management. It is possible that in a person with CAD, it may mask the symptoms of CA. Ischemic cardiomyopathy resulting in heart failure symptoms may prolong the diagnosis of cardiac amyloidosis. An issue arises when medical therapy with beta-blockers and ACEI/ARBs are indicated for ischemic cardiomyopathy but avoided in CA. Patients with triple vessel CAD with known CA need to be considered for percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG). The benefits of CABG over PCI in triple vessel disease with diabetes are typically seen in the long run. It is still unclear precisely if CA contributes to AS or if they are independent and association is merely age-related. Deposition of amyloid fibrils on the valve resulting in AS argues for CA contributing to AS. Recent data suggest that combined AS-CA is associated with worse 1-year-mortality compared to lone AS., Previously, ATTR amyloidosis therapies were not vastly available and approved. Now with TTR stabilizer and silencer therapy available, various new areas to explore are available. Two questions are critical to avoid such an increased risk of heart block; 1) Whether patients with severe AS undergoing TAVR should be routinely tested for CA? 2) If they are tested and found to have ATTR CA, should they receive a trial of TTR stabilizer/silencer medication prior to valve intervention? Data regarding this is lacking at this point.Aortic stenosis (AS) and its association with CA are well known now, with studies showing the incidence of CA in AS patients undergoing valve replacement as high as 29%.et al. on patients referred for liver transplants tried to answer this question. Data did not suggest improved mortality or morbidity in patients who received a PPM before liver transplantation for prophylaxis. A recent study by Porcariet al. noted that 8.9% of patients with the diagnosis of CA needed PPM implantation within 3 years of diagnosis. Thus, until further data is available, it is reasonable to reserve pacemaker placement for secondary prevention.Pacemaker implantation is seen frequently in patients with CA who develop conduction disorders. These are the patients who develop symptomatic bradycardia or high-degree atrioventricular block. The question that arises with this is, can pacemaker implantation be considered in high-risk individuals for primary prevention? There has been sparse data regarding the role of permanent pacemaker implantation (PPM) for primary prevention and the optimal time to pursue such a step. A recent study by Milner Traditionally indicated for patients with LVEF <35% with left bundle branch block and QRS >150 ms; theoretically, it also plays a role in CA. Infiltrative cardiomyopathies in which RV pacing leads to LV systolic dysfunction, and when AV conduction block is associated with LV dysfunction, CRT may be indicated. Detailed data on CRT in patients with CA is lacking. A recent study on major cardiovascular events and outcomes after CRT implantation in CA patients has not shown any benefit and has suggested that it may be associated with worsened HF symptoms and hospitalization. Compared to dilated cardiomyopathy, CRT had much lower response rates in patients with CA.Cardiac resynchronization therapy (CRT) has been previously suggested to be used for patients in whom a high-paced burden is expected who are undergoing pacemaker placement. However, its role in the primary prevention of SCD in patients with CA is not established. Nonetheless, recent case reports have opened a new discussion area in this matter. Patients with cardiac amyloidosis who develop non-sustained ventricular tachycardia may not qualify for ICD placement just yet but do qualify for an electrophysiological study (EPS) to identify a potential area of the arrhythmogenic substrate for ventricular tachycardia. Further studies are needed for risk stratification and establishing guidelines regarding primary ICD in such patients.An implantable cardiac defibrillator (ICD) has a role in the primary prevention of sudden cardiac death in patients with LVEF <35%. Electromechanical dissociation is likely the cause behind SCD in CA. ICD placement is recommended in CA for secondary prevention after the patient has developed sustained ventricular tachycardia.Cardiac transplantation has been performed for decades in patients with cardiac amyloidosis, particularly AL amyloidosis. However, outcomes were not favorable previously. This was secondary to extracardiac involvement and limitations of chemotherapy options. With the advent of advanced chemotherapy given even after cardiac transplantation and better diagnostic techniques allowing extracardiac detection, proper candidates are being chosen for cardiac transplantation associated with improved outcomes.Mechanical circulatory support (MCS) has not been studied adequately in CA. Being restrictive cardiomyopathy, to implant assist devices in CA with small cardiac cavities is technically challenging. If selective left ventricular assist devices are placed, it increases the risk of right-sided heart failure. Also, considering patients with CA being on active immunosuppressive therapy, the risk of infection needs to be considered. Despite these factors, there has been recent data to suggest a role of MCS in patients with left ventricular end-diastolic diameter >46 mm. Even if performed as a bridge to transplantation, MCS is associated with increased survival. In a recent study, bortezomib is shown to have a significant hematological response and improved survival. Various regimens have been studied, but no regimen is found to be superior to others. Newer therapies with anti-CD38 human IgG monoclonal antibody agents daratumumab and isatuximab are currently under investigation, with preliminary data showing better short-term outcomes.AL amyloidosis is managed with various chemotherapy agents. Oral melphalan with steroids has been used for treatment for an extended period. Autologous stem cell transplant and melphalan became the mainstay of treatment in the 1990s and remained robust treatment options. However, the introduction of proteasome inhibitors revolutionized the treatment of AL amyloidosis with the enteral agent of bortezomib. Patients with ATTR CA treated with Tafamidis have had reduced CV-related hospitalizations and length of stay in the hospital. The most significant barrier to tafamidis being widely used is its cost-effectiveness. Even with insurance, it is estimated that the cost of production of tafamidis may need to be reduced by >90% for it to be cost-effective.,ATTR amyloidosis therapies are aimed at two mechanisms. One is to silence the TTR gene, and the other is to stabilize the TTR tetramers preventing them from forming monomers and thus constituting amyloid fibrils. TTR stabilizer includes Tafamidis and Diflunisal, showing promising data with substantially improved long-term outcomes in recent studies. Another gene silencer medication Inotersen has shown similar improvement. Many patients with ATTRv amyloidosis may have a mixed phenotype of cardiomyopathy and polyneuropathy. These patients can be considered for either TTR stabilizer or gene silencer therapies. Current practice and guidelines recommend selecting medication based on the predominance of cardiac or neurological phenotype. However, data to support this approach is not conclusive. Given their mechanism of action, gene silencer medications may be even more effective than TTR stabilizer medications in managing ATTR CA.Gene silencer therapy with Patisiran has been studied in ATTRv and has shown significant improvement in neurological symptoms in patients with ATTRv amyloidosis after liver transplantation. Clinical trials are ongoing, focusing on new therapies such as vutrisiran, AG10, doxycycline, green tea, and monoclonal antibody NNC6019-0001 for their role in managing ATTR CA.Most recently, targeted delivery of gene-editing therapy with the Cas9 endonuclease (CRISPR-Cas9) system to the hepatocytes is being studied. This is a single infusion and reduces the production of transthyretin by the hepatocytes.Many recent advances have been made in diagnosing and managing cardiac complications of amyloidosis and disease-modifying treatment. Bone scintigraphy has played a pivotal role in early, non-invasive diagnosis coupled with disease-modifying therapy with medications such as Tafamidis and Bortezomib have changed the perception of CA. With better diagnostic capabilities, cardiac complications need to associate with CA and be managed based on specific guidelines obtained from data of CA patients. This opens new doors for research questions. Management of triple vessel CAD with co-existent CA with PCI versus CABG, routine PYP scan prior to TAVR, a trial of Tafamidis prior to valve intervention, ICD for primary prevention of SCD in CA after EP study, MCS in patients with adequately sized cardiac chambers are few of such questions which we have raised and hypothesized in this article.MR prepared the manuscript with the help of LS, AJ, SP, JT, KUC, DP, and RD. SS and KS are the senior authors who helped revise the manuscript and reviewed it for intellectual content. This is a comprehensive review of cardiac amyloidosis. Figure 1 was a good overview. A good number of resources were cited. The authors provided a detailed oriented review of cardiac amyloidosis and advances in the field. The information provided is thorough and has efficiently summarized the management strategies and disease modifying therapies. I did not answer "no" or "partly" to any questions.Is the review written in accessible language?YesAre all factual statements correct and adequately supported by citations?YesAre the conclusions drawn appropriate in the context of the current research literature?YesIs the topic of the review discussed comprehensively in the context of the current literature?YesReviewer Expertise:Internal MedicineI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. An excellent report in reviewing the key aspects of cardiac amyloidosis focusing on recent advances and current literature. All statements appear to be factual, and the language is appropriate. It has detailed recommendations of recent advances in management with adequate and appropriate citations and the conclusions are made in accordance with the current literature.Is the review written in accessible language?YesAre all factual statements correct and adequately supported by citations?YesAre the conclusions drawn appropriate in the context of the current research literature?YesIs the topic of the review discussed comprehensively in the context of the current literature?YesReviewer Expertise:Areas of interest and research are endocrinology, immunology, neurology.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Even though congenital heart disease is a common finding in down syndrome (DS) patients, some of them have anatomically normal hearts. However, the term “normal” might not be suitable, as these patients usually suffer from functional cardiac dysfunction. Several research highlighted that despite the absence of anatomical heart defects, subtle cardiac function derangements are present in DS patients. We aim to assess cardiac functions by Two-dimensional echocardiography and tissue Doppler imaging (TDI) in pediatric DS patients who have anatomically normal hearts. One hundred seventy-two patients with karyotyping confirmed DS with anatomically normal hearts and 165 healthy normal control children were enrolled in the current study. Their cardiac functions were assessed using both 2-dimensional echocardiography and TDI. Both patients and controls had structurally and anatomically normal hearts. In DS patients, the right side of the heart showed a significant reduction in both systolic and diastolic functions. Systolic dysfunction was evident by significantly decreased levels of Tricuspid annular plane systolic excursion and systolic wave by TDI. Diastolic dysfunction of the right ventricle was evident by prolonged deceleration time by conventional echocardiography and a significant decrease in annular tissue doppler velocity during early diastole/late diastole ratio by TDI. The E/De ratio was significantly increased. Even with anatomically normal hearts, DS patients should undergo cardiac function assessment by echocardiography & TDI. TDI is superior to conventional echocardiography in detecting subtle cardiac dysfunction especially left ventricular diastolic dysfunction in DS patients. TDI showed a significant decrease in the early/atrial ratio of mitral valve annulus and prolongation of left ventricle isometric relaxation time in DS children. Also, the left ventricle E/De ratio was prolonged denoting elevated filling pressures and diastolic dysfunction. This indicates that the TDI has higher sensitivity to detect diastolic dysfunction than conventional Echocardiography. Biventricular TDI-derived myocardial performance index was found to be significantly increased in DS children. Examining cardiac function in this vulnerable population is critical to identify risk for decreased exercise capacity and increased risk for morbidity.We retrospectively reviewed medical records of the pediatrics, pediatric cardiology, and pediatric genetic outpatients’ clinics of Benha University Specialized Children Hospital, Benha, over the period between December 2018 and January 2022, for all DS patients who have an anatomically normal heart. Patients with DS and anatomically normal hearts were then prospectively evaluated thoroughly (refer to the methods section). For the control group, we recruited a comparable number of normally matched age and sex children.The study was approved by the local institutional review board of Benha University. Written informed consents were obtained from the guardians of all patients and controls for the contribution to the study and for the of the study data.Pediatric and adolescents DS patients.Age 6 months- 18 years.DS genetically proven by karyotyping.Normal chest X ray (CXR) & electrocardiogram (ECG).Anatomically normal heart by echocardiography .Negative history of chronic diseases.Associated congenital or acquired heart disease.Associated pulmonary hypertension of any cause.Any chronic pulmonary disease or upper airway obstruction.Uncontrolled bronchial asthma.Peripheral or central hypoventilation.Thoracic skeletal deformities.Obstructive sleep apnea excluded by the sleep studie.Tonsillo-adenoidal hypertrophy.Hypothyroidism.Full history taking: Age, sex, maternal age, cardiac symptoms, and other body symptomatology review.Thorough clinical examination: Anthropometric measurements , vital signs , and ear, nose, throat, respiratory, cardiovascular, and other body systems examination.Radiological workup by CXR.ECG: for detection of any cardiac arrhythmia.Conventional echocardiography:Detailed conventional echocardiography was performed at the Pediatric Cardiology Unit, Benha University Hospitals. It was done using Hewlett Packard/Phillips SONOS 5500 systems–Palo Alto, California – equipped with 2.5 to 5 megahertz transducers.It included measurements of the following: An EF of < 55% was considered abnormal and FS of < 29% was considered abnormal.Left ventricular dimensions at end-systole and end-diastole, interventricular septum, ejection fraction (EF) estimated by cube method, and fraction shortening (FS) evaluated by M-mode echocardiography in the parasternal short axis. All measurements were compared to standard tables for ages and body surface area.Mitral & tricuspid Doppler signals evaluated in the apical 4-chamber view: early diastolic peak velocity , mitral deceleration time of early filling (DCC) in milliseconds, late diastolic peak velocity , and early/late diastolic peak velocity ratio (E/A).Assessment of pulmonary artery (PA) systolic pressure via tricuspid regurgitation jet using the Bernoulli equation.Assessment of mitral annular plane systolic excursion using the M-mode in apical 4-chamber view & tricuspid annular plane systolic excursion (TAPSE) using the M-mode in apical 4-chamber view, placing the examination beam on the lateral mitral & tricuspid annuluses.Tissue-Doppler-Imaging:TDI was obtained from an apical 4-chamber view to obtain longitudinal annular velocities at the lateral mitral wall, septum, and lateral tricuspid wall adjacent to the atrioventricular valve hinge points. annular tissue doppler velocity during systole (Sa), early diastolic (De), and late diastolic (Da) tissue Doppler velocities, isovolumetric contraction, and relaxation times will be measured at the lateral mitral, septal, and lateral tricuspid walls. Trans mitral and trans tricuspid E/Ea ratios, ejection time for anterior wall, posterior wall, and septum, and myocardial performance index for them were calculated for each patient.P > .05.SPSS version 22 was used to tabulate and analyze the gathered data . Percentages and numbers were calculated for categorical data. The Chi-square test (X2), or Fisher exact test was used to analyze categorical variables. Quantitative data were tested for normality using the Kolmogorov-Smirnov test assuming normality at t test was used to evaluate regularly distributed variables between 2 independent groups. The accepted level of significance was 0.05 (P < .05 was considered significant).Variables such as means, standard deviations, and ranges were used for quantitative data. Mann–Whitney U test was used for nonparametric variables and the student Over the study period, 172 genetically proven pediatric DS patients fulfilling the study inclusion criteria were enrolled in the current study. All patients had normal CXR, ECG, and absent anatomical cardiac lesions by echocardiography as prerequisites for enrollment. One hundred sixty-five healthy children who were age and sex-matched served as the control group.P < .001)  in patients and controls revealed, significantly lower left ventricular end-diastolic dimensions & left ventricular end-systolic dimensions dimensions, while their EF, FS, and E & A velocities were significantly higher than that of controls Table .On the other hand, a comparison of the echocardiographic assessments of the right ventricle (RV) in patients and controls revealed, significantly lower TAPSE while the E & A velocities, the right ventricle DCC time, tricuspid regurgitation, and EPASP were significantly higher in patients than controls Table .No intergroup differences were detected regarding left ventricular DCC time and E/A ratio for both LV & RV Table .TDI evaluation of the LV showed that; LV isovolumetric contraction and relaxation times, E/De ratio, and MPI were significantly higher in patients. The mitral annulus Sa wave, De wave, De/Da ratio, and ejection time were significantly lower in patients compared to controls Table .TDI evaluation of the RV showed that; the tricuspid annulus Sa & De waves, De/Da ratio, and RV ejection time are significantly lower in patients as compared to controls. On the other hand, patients had significantly higher tricuspid annulus Da wave, RV isovolumetric contraction & relaxation times, E/De ratio, and MPI Table .No intergroup difference was detected regarding the mitral annulus Da wave Table . Owing to the fact that this causes a high burden on the community and health care system and the high prevalence of DS patients worldwide, there is an urgent necessity for a proper integrated follow-up and management plan for those patients.DS is one of the most common chromosomal abnormalities in humans characterized by a wide phenotypic variation of multiple cardiac as well as systemic complications. which in turn affects their quality of life. It was found that even in absence of congenital cardiac defects, DS patients have diminished cardiac capacity.,14 This might be attributed to their baseline-associated hypotonia and to subtle cardiac functions abnormalities, myocardial fibrillar structure, and autonomic nervous system dysfunctions even in absence of anatomical congenital cardiac defects.,14 Pastore et al, 2000 showed that children with DS without congenital heart disease have a reduced tolerance for exercise, higher heart rates, and higher arterial blood pressure. However, no symptoms  or arrhythmias occurred during exercise.Cardiac assessment is core care in all DS patients due to the high association with congenital heart disease (40%–60%),16,17 This might be explained by a better understanding of the physicians & better education of the parents that regular follow-up of DS patients is mandatory despite the absence of cardiac abnormalities. Previously, it was assumed that in the absence of anatomical cardiac defects, no cardiological follow-up was needed which contributed to the delayed presentation of functional cardiac abnormalities at older ages in previous studies. Hospitals should have integrated DS clinics providing multidisciplinary care plans for the different health needs of DS patients.We carried out this study to assess cardiac dysfunction in DS patients with anatomically normal hearts. All patients underwent both 2-dimensional- echocardiography and TDI. One hundred seventy-two DS patients fulfilling the study inclusion criteria were enrolled in the study. Their median age was 4.8 years (range: 0.62–16.63) which was younger than the age reported in the previous studies. & Balli et al respectively, while Youssef & Raouf had a reverse ratio (0.8: 1). No clear significance/explanation of those finding was found in the literature.Fifty-eight percent of our patients were males with a male-female ratio of 1.4:1, which was statistically insignificant. A similar finding of 1.3:1 & 1.9:1 was reported before by Al-Biltagi et al,19 The significantly shorter height in the DS group was also expected as an invariable feature of DS.The significantly higher maternal age in the DS group is a well-known association with DS detected in our report and in all previous literature. in having significantly higher BMI in the DS group. Balli et al detected insignificant higher BMI in their DS patients. The higher BMI may be related to decreased physical activity of DS patients.We agreed with Al-Biltagi et al,16,17 Santoro et al, 2020 found that there is a 12-percentile point reduction in baseline BP in pediatric DS patients with normal hearts compared with age- and height-matched controls as reported in the standard national heart, lung, and blood institute/national health and nutrition examination survey and AAP cohorts. This might be explained by the associated autonomic cardiac dysregulation in DS patients due to the associated brain stem central autonomic dysfunction in DS patients. This has also been observed in the form of blunted heart rate and blood pressure responses to tilt-table testing. The lower blood pressure in those patients might be related to the trisomy of the type-1-angiotensin II receptor gene, resulting in its repression.Assessment of the vital signs revealed, significantly higher HR & RR & lower systolic BP in the DS group, while they had insignificantly lower diastolic BP. Those findings were also reported in previous studies.,16 This hyperkinesia is mostly attributed to the reduced afterload in DS patients due to trisomy of the type-1-angiotensin II receptor gene.Regarding conventional Echocardiography, the LV EF & FS were significantly higher in DS children. These results were similar to previous reports.However, the presence of intrinsic myocardial abnormalities in DS patients, even with structurally normal hearts was proven by subtle systolic dysfunction detected by TDI.P value of .01. Isovolumetric contraction time was significantly prolonged in children with DS with a P < .001.Sa wave on the mitral valve was significantly decreased in our DS cohort as compared to controls with values of 7.11 cm/s and 7.52 cm/s respectively with a  demonstrated a lack of significant difference between systolic wave and ICT of the mitral valve annulus measured by TDI between DS children and the controls.Sa wave is less load dependent, whereas the isometric contraction time (ICT) is inversely correlated with myocardial contractility. Al- Biltagi et alP values 1.0 and 0.5 respectively. These results were conflicting with Balli et al who found a significant decrease in the E/A ratio on the mitral valve in DS children compared to controls.Our results showed an insignificant difference between the E/A ratio or DCC on the mitral valve by the conventional Echocardiography with P < .001). Moreover, the LV E/De ratio was prolonged denoting elevated filling pressures and diastolic dysfunction. This may be due to the higher sensitivity of the TDI to detect diastolic dysfunction in comparison to conventional Echocardiography.However, TDI showed a significant decrease in the early/atrial ratio of mitral valve annulus and prolongation of LV isometric relaxation time in the DS children than in the controls (,17Diastolic dysfunction in DS is most probably due to impaired cardiac muscle relaxation. This was agreed with previous reports. We excluded patients with chronic upper airway obstruction from our cohort.Children with DS are at increased risk of developing PA hypertension even without structural heart lesions. In the current study, the estimated systolic PA pressure was significantly higher in children with DS. This can be explained by abnormal pulmonary vasculature, alveolar hypoventilation, and recurrent pulmonary infections.P < .001.The right side of the heart showed significant reduction in both systolic and diastolic functions by conventional Echocardiography and TDI on the tricuspid valve. Systolic dysfunction was evident by significantly decreased levels of TAPSE and Sa by TDI. ICT was also prolonged significantly with a  who concluded that the reduction of the systolic and diastolic cardiac functions in children with DS may be explained by cardiac autonomic dysregulation, increased cardiac muscle fiber size, reduced cell number, and overexpression of calcineurin.Diastolic dysfunction of the RV was detected by prolonged DCC by conventional echocardiography and a significant decrease in De/Da ratio by TDI. The isometric relaxation time & RV E/De ratio was significantly increased. These results are concordant with Al Biltagi and coresearchers,B-ventricular TDI-derived myocardial performance index was found to be significantly increased in DS children compared to controls, which confirms subclinical ventricular dysfunction in DS children with anatomically and clinically normal hearts. This was agreed with Abtahi and coauthors.In conclusion, even with anatomically normal hearts, DS patients should undergo cardiac functions assessment by both echocardiography & TDI. TDI is superior to conventional echocardiography in detecting subtle cardiac dysfunction especially left ventricular diastolic dysfunction in DS patients.Conceptualization: Eman G Abdelrahman.Data curation: Eman G Abdelrahman, Effat Assar.Formal analysis: Eman G Abdelrahman.Investigation: Eman G Abdelrahman, Effat Assar.Methodology: Effat Assar.Validation: Eman G Abdelrahman.Writing – original draft: Eman G Abdelrahman, Naglaa M Kamal, Sultan Alharthi, Muflih Albalawi, Effat Assar.Writing – review & editing: Eman G Abdelrahman, Naglaa M Kamal, Sultan Alharthi, Muflih Albalawi.


Obesity and atrial fibrillation in the elderly population both present as significant health issues worldwide indirectly. Cases of atrial fibrillation are also rising worldwide, making it the most common type of cardiac arrhythmia. There are a variety of risk factors for atrial fibrillation. Modifiable factors include smoking, hypertension, diabetes mellitus, sedentary lifestyle, obesity, and non-modifiable include genetic predisposition. Obesity is a well-known risk factor for multiple systemic conditions like metabolic syndrome, diabetes mellitus type 2, sleep-related disorders, etc. In addition, it contributes directly to the development of various cardiovascular disorders like hypertension, myocardial infarction, and, more notably, atrial fibrillation. There are multiple mechanisms by which obesity in adults increases the risk of atrial fibrillation. Some of them are systemic inflammation caused by the increased secretion of cytokines by adipocytes, neuro-hormonal disturbances and heart structure remodeling, and weight-loss strategies have shown improvements in patients suffering from atrial fibrillation. Caballero suggests that more than two billion people suffer from this growing epidemic [Atrial fibrillation, a commonly occurring cardiac arrhythmia, affects three to six million general population in the United States . It accoepidemic . Increasepidemic , with obepidemic . Obesityepidemic . A populepidemic . In anotepidemic . Studiesepidemic . Variousepidemic . Animal epidemic . The relepidemic .PathophysiologyObesity causes hemodynamic changes that alter cardiac morphology and physiology ,16. It iGene expression of all renin-angiotensin-aldosterone system (RAAS) components, including aldosterone, increases in obese patients . AldosteEpicardial adipose tissue (EAT) is adipose tissue surrounding the heart, located between the myocardium and the visceral pericardium , and metUntil now, it has been established how obesity is associated with AF. However, a 12-month longitudinal observational study done by Rodriguez-Reyes et al. on patients with documented atrial fibrillation concludes that mortality in these patients was inversely related to high BMI . Meta-anDiagnosis and treatmentDiagnosisPatients with atrial fibrillation can present with mild or no symptoms. Atrial fibrillation can also be found in patients with other conditions such as congestive heart failure, myocardial infarction, stroke, or shock. A prospective study showed that coronary artery disease was seen in 70% of the patients suffering from atrial fibrillation and hence it is also vital to rule out any co-existent coronary artery disease . A detaiInitial laboratory work to evaluate the cause of atrial fibrillation includes a complete blood count, a basic metabolic panel for electrolyte abnormalities, and thyroid function tests to assess for hyperthyroidism, blood alcohol, and other illicit drug levels. It is also important to assess cardiac biomarkers and B-type natriuretic peptides to determine any underlying cardiac disease such as myocardial ischemia, myocardial infarction, or heart failure. Transthoracic echocardiography should be done to rule out structural heart diseases, like atrial septal defects and valvular diseases, and a chest x-ray to rule out pulmonary diseases.TreatmentManagement includes lifestyle modification, risk factor management, weight loss, rate and rhythm control, and anticoagulation. Studies have shown the positive effect of weight loss and risk factor management on atrial fibrillation progression and recurrence . For exa2) have significantly higher warfarin requirements than patients with lower BMI. Direct oral anticoagulants would be an alternative to warfarin, but minimal clinical trial data exists in patients with high BMI. A study by Martin et al. in 2016 suggests the avoidance of direct oral anticoagulants (DOACs) in morbidly obese patients due to limited clinical data [2 or >120 kg/m2 [A patient’s high BMI can change the pharmacodynamics and pharmacokinetics of warfarin. Anticoagulation is one of the pillars of atrial fibrillation management to minimize thromboembolic risk . Patientcal data . Some st20 kg/m2 .Another component of atrial fibrillation management is rhythm control with direct current cardioversion (DCCV). This facilitates quick evaluations of symptoms and assesses cardiac dimensions and function changes while in sinus rhythm. Patients with higher BMI have shown lower success rates with cardioversion . Due to Atrial fibrillation is a common arrhythmia and a significant cause of cardiovascular mortality. The prevalence of obesity is also rising, and it has been classified as an epidemic by various studies. Obesity has long been known to increase the risk of various cardiovascular diseases, and its role in causing atrial fibrillation is undisputed. There are multiple mechanisms, like the structural remodeling of the heart, epicardial adipose tissue, and inflammatory markers secreted by the fatty tissues which may lead to atrial fibrillation in obese adult population. The causal relationship is also evident because the studies done over the years have reported a positive role of weight loss in treating and preventing atrial fibrillation in obese patients. Apart from weight loss and lifestyle modification, rate and rhythm control complete the management of atrial fibrillation. Our study is limited only to the adult population and is a narrative review that does not provide any statistically significant association between obesity and atrial fibrillation. More extensive research is needed to strengthen this association with strategies to prevent obesity and associated atrial fibrillation.


The compressive moduli of the cross-linked PAM/MsCa and PAM/KCa aerogels greatly increased to 17.4 and 22.1 MPa, approximately 10.5- and 8.2-fold of that of PAM aerogel, respectively. The limited oxygen index (LOI) values for PAM/MsCa and PAM/KCa composite aerogels increased from 27.0% of PAM aerogel to 40.5% and 56.8%. Compared with non-cross-linked PAM aerogel, the peak heat release rate (PHRR) of PAM/MsCa and PAM/KCa composite aerogels dramatically decreased by 34% and 74%, respectively, whereas the PAM/KCa aerogel presented better flame retardancy and lower smoke toxicity than the PAM/MsCa aerogel because of the release of more inert gases and the barrier action of more compact char layer during the combustion. The highly efficient flame-retardant PAM-based composite aerogels with excellent mechanical properties are promising as a sustainable alternative to traditional petroleum-based foams.Poly (P)/alginate (A)/MMT (M) (PAM) composite aerogels was modified through interpenetrating cross-linking of methyltriethoxysilane (Ms) or γ-aminopropyltriethoxysilane (K) and calcium ion (Ca Aerogels are promising materials in a wide range of fields, including supercapacitor ,2, electVarious inorganic micro- and nano-fillers, such as montmorillonite , graphen2 [Nowadays, the mechanical properties of polymer aerogels were enhanced by the incorporation of various cross-linking agents, such as aldehydes , divinyl2 , and bio2 . For exa2 . The cro2 . The PVA2 .2 as a cross-linker, respectively. The influence of two kinds of silane cross-linking agents with different structures (such as MTMS and APTS) on the morphology and compressive properties of PVA-based composite aerogels were compared, and the flame-retardant performance and its flame-retardant mechanisms of the as-prepared cross-linked PVA-based composites were systematically investigated.Methyltriethoxysilane (MTES) and γ-aminopropyltriethoxysilane (APTS) are both important silane coupling agents and the multi-hydroxyl formed by the hydrolysis of silane could produce cross-linking network with PVA hydrogel, in order to enhance the mechanical property of the aerogels. Silane as a coupling modifier of fillers can improve the interfacial compatibility between fillers and polymer matrix. However, a small amount of the literatures reported the influence of silanes with different structures as the cross-linking agents on the morphology and mechanical properties of aerogels. In this manuscript, a series of highly efficient flame-retardant PAM composites aerogels were fabricated by the incorporation of different silane and CaCl2 was purchased from Shanghai Sinopharm Chemical Reagent Co., Ltd., Shanghai, China.Poly  was supplied from Shanghai Epi Chemical Reagent Co., Ltd., Shanghai, China. Sodium alginate (A) was purchased from Tianjin Zhiyuan Reagent Co., Ltd., Tianjin, China. Montmorillonite (MMT) was produced from Shijiazhuang Chenxi Refractory Materials Co., Ltd., Shijiazhuang, China. Methyltriethoxysilane (MTMS or Ms) and γ-aminopropyl-triethoxysilane (APTS or K) were purchased from Zhejiang Chemical Technology Co., Ltd., Hangzhou, China. CaClA PAM composite hydrogel was prepared according to the previous literature, and the weight ratios of PVA, alginate, and MMT components were 4 wt%:4 wt%:4 wt% in deionized water, respectively . The pH 2 saturated ethanol solution for 12 h at 20 °C, and then it was dried to remove ethanol in a vacuum oven at 60 °C for 12 h. The resulting cross-linked PAM aerogel were referred as PAM/MsCa and PAM/KCa aerogels, respectively. The preparation process of the different cross-linked PAM composite aerogels is presented in The PAM/Ms or PAM/K aerogel was further cross-linked in a CaCl−1, and the crystalline structure of the sample was characterized using a D/Max-2500 type X-ray diffraction (XRD) instrument in the 2θ range from 4° to 60° at room temperature. The thermal property of the sample was measured by a Q500 Thermogravimetric Analyzer  at 10 °C/min from 25 to 700 °C under N2 atmosphere. The morphology of the sample was observed by a SM-6700F scanning electron microscopy (SEM) , and the surface elemental compositions of the sample were measured by an INCA type energy dispersive spectrometer (EDS).The microstructure of the aerogels was firstly characterized by a Vertex 70 type Fourier-transform infrared (FT-IR) spectrometer , using a KBr disk in the wavenumber range of 4000–400 cmCompressive properties of the cylindrical aerogel specimens (the size of sample: 2 cm in diameter and 2 cm in height) were measured using a Zwick Z020 Universal Testing Machine , with a load of 5000 N and a compression rate of 10 mm/min.3) was measured to obtain a UL-94 vertical burning rating, according to ASTM D3801-2010 by a CZF-2 type instrument . The limited oxygen index (LOI) values of the aerogel samples (120 × 10 × 10 mm3) were measured according to ASTM D2863-2009 by a HC-2C type oxygen-index meter . Cone calorimeter test of the aerogel samples (100 × 10 × 10 mm3) was conducted according to ASTM E1354/ISO 5660 by a cone calorimeter  at a heat flux of 35 kW/m2.Flame retardant performance of the aerogel samples (125 × 10 × 10 mm2) groups of APTS with hydroxy(–OH) groups of PVA and SA in the PAM/K hydrogel was enhanced; thus, the size of pores for the PAM/K aerogel became smaller and, thus, the pore size of the PAM/K aerogel became smaller than that of PAM/Ms aerogel, and the pore distribution of the PAM/K aerogel was more uniform than that of PAM/M aerogel  of Ca-alginate particles of PAM/KCa aerogel than that of PAM/MsCa aerogel.After the step-by-step cross-linking of the PAM aerogel with silanes and of calcium ions, the bubble pore structures of the PAM/MsCa and PAM/KCa aerogels became more compact than those of the PAM aerogel  network mechanism of the different PAM aerogels was illustrated in For the PAM/MsCa and PAM/KCa composite aerogel, the diffraction peaks of alginate at 32.24° shifted to 32.20 and 31.40°, respectively, which were ascribed to the “egg–box” cross-linked structure between CaThe mechanical performance of the different PAM cross-linked aerogels is shown in 2/s2, approximately 109% and 86% higher that of the PAM aerogel, respectively. It was because the MTMS or APTS as cross-linking agent enhanced the cross-linking densities of the PAM/Ms or PAM/K aerogel. The compressive moduli of the PAM/MsCa and PAM/KCa aerogels further increased to 17.4 and 22.1 MPa, 2.3- and 2.8-fold higher than those of the PAM/Ms and PAM/K aerogels, respectively. The specific moduli of the cross-linked PAM/MsCa and PAM/KCa aerogels also obviously increased, which was because in situ formed calcium alginate particles entered the three-dimensional network structure as physical cross-linking points at the bubble wall, resulting in an apparent improvement of the compressive properties of the PAM aerogels. In addition, the compressive modulus of the PAM/KCa aerogel was higher than that of the PAM/MsCa aerogel, which was attributed to that of the amino groups of APTS, which enhanced the hydrogen-bond interaction of the PAM/KCa aerogel.As shown in T5%) of the PAM/Ms aerogel decreased to 234.0 °C (max1T) increased to 301.9 °C, and the corresponding maximum thermogravimetric loss rate (dW/dt) increased to 7.7%·min−1, which were mainly due to the dehydration reaction between PVA, SA, and hydroxylateds silane. For the PAM/K aerogel, the T5% and max1T further reduced, and the second maximum dW/dt concomitantly increased, which were mainly attributed to the decomposition of amino- and alkyl groups of the cross-linked PAM/K aerogel, thus leading to the decrease of the residue yields of the PAM/Ms and PAM/K aerogels at 700 °C to 51.5% and 46.2%, respectively. For the PAM/MsCa and PAM/KCa aerogels, the max1T and max2T values were higher than those of the PAM/Ms and PAM/K aerogels, and the corresponding maximum weight loss rates decreased from 6.3%/min of the PAM aerogels to 1.8%/min and 2.9%/min; hence, the residue yields of the PAM/MsCa and PAM/KCa aerogels increased to 64.1% and 49.6%, respectively. The incorporation of Ca-alginate particles promoted the formation of the residues. Thus, the char yield of the PAM/MsCa and PAM/KCa aerogels were obviously higher than the corresponding PAM/Ms and PAM/K aerogels, respectively.The thermal decomposition process and thermal stability of the different PAM composite aerogels were investigated, and the corresponding thermogravimetric (TG) and differential thermogravimetric (DTG) curves are shown in 234.0 °C , the firThe flame-retardant performance of the different PAM aerogels is listed in 2, whereas the first PHRR value of the PAM/K aerogel increased to 112.2 kW/m2. This was mainly attributed to that the silanes as cross-linking agents were decomposed to produce some flammable gases during combustion. Thus, the THR values  is the ratio of the ignition time (TTI) to PHRR. The TTI and FPI values of the PAM/Ms and PAM/K composite aerogels had no obvious change , whereas−2·g−1, respectively, because the decomposition of combustible gases in the PAM/Ms and PAM/K aerogels in the gas phase resulted in the slight decrease in the flame retardancy. The THR/TML values of the PAM/MCa and PAM/KCa aerogels obviously decreased to 0.51 and 0.46 MJ·m−2·g−1, respectively, because the decomposed inert gases  of the PAM/MsCa and PAM/KCa aerogels in the gas phase were conductive to the improvement of flame retardancy.THR/TML value (the heat release rate per gas mass) is a commonly used parameter to analyze the flame retardant mechanism in the gas phase, and the reduction of THR/THL value indicate there is a gaseous flame retardant mechanism in the flame-retardant polymer materials ,40. The The digital photographs and SEM images with different magnification of the char residues for the different PAM aerogels after cone calorimeter test could be compared in 3) of calcium alginate  were released from the cross-linked PAM/KCa aerogels than those of PAM/MsCa aerogel, and the denser residue in the PAM/KCa aerogel was also more beneficial to insulate heat transfer and the diffusion of the small molecule combustible gases. As a result, the flame retardancy of the PAM/KCa aerogel is better than that of the PAM/MsCa aerogel.The average relative weight compositions of C and O elements in the PAM/Ms and PAM/K residues by EDS decreased, compared with those of the PAM aerogel a, which eculated b, and moA series of highly efficient flame-retardant PAM composite aerogels were fabricated. After the cross-linking of silanes, the cell densities of the PAM/Ms and PAM/K aerogels increased, and the compressive moduli was obviously enhanced. However, the flame retardancy of the PAM/Ms and PAM/K slightly decreased. The compressive moduli of the PAM/MsCa and PAM/KCa aerogels dramatically increased through interpenetrating cross-linking network, approximately 10.5- and 8.2-fold of that of PAM aerogel, respectively. Meanwhile, the LOI values of the PAM/MsCa and PAM/KCa aerogels greatly increased to 40.5% and 56.8%, respectively. The cone calorimeter result indicates that the flame retardancy of PAM/MsCa and PAM/KCa composite aerogels obviously improved, and the smoke toxicity was greatly suppressed. The high flame-retardant PAM composite aerogels are promising in the flame-retardant material fields as an alternative to petroleum-based foams.


Pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals is a complex congenital heart defect that includes a heterogeneous subgroup of patients. Variation in the sources of pulmonary blood flow contributes to the complexity of the lesion and the diversity of approaches to its management. Unifocalization and rehabilitation focus on mobilization of collateral arteries and growth of native pulmonary arteries, respectively, with the ultimate surgical goal of achieving separated systemic and pulmonary circulations with the lowest possible right ventricular pressure. Regardless of the strategy, outcomes have altered the natural history of the disease, with a complete repair rate of approximately 80% and low early and late mortality rates. Given this heterogeneity of pulmonary vasculature, a tailored approach should be adopted for each patient, using all diagnostic methods currently offered by technical developments. Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCAs) is a complex congenital heart defect that includes a heterogeneous subgroup of patients characterized by different pulmonary perfusion patterns, of which MAPCAs are an important, although not the only source. True pulmonary arteries may have varying degrees of hypoplasia, be absent and, more rarely, discontinuous, with unilateral pulmonary perfusion provided by the arterial duct and contralateral by MAPCAs ,2. The vThe ideal end goal of treatment is to establish pulmonary blood flow from the right ventricle (RV) to as normal a pulmonary vascular bed as possible to allow VSD closure with the lowest possible RV pressure after repair. In order to pursue this aim, however, a structured approach based on a thorough understanding of the anatomical characteristics of each patient is required. At our center, every patient with PA/VSD/MAPCAs first receives cardiopulmonary imaging by computed tomography (CT). Given its non-invasiveness, CT is suitable for diagnosis in the neonatal period and allows to decide at the patient’s initial presentation which surgical procedure should be considered, i.e., either unifocalization or pulmonary circulation rehabilitation. In most patients, treatment of the disease in the neonatal period is not required, and the diagnosis is supplemented by cardiac catheterization in the vicinity of surgery. Cardiac catheterization plays a key role in the preoperative evaluation and is considered an essential step. The purpose of cardiac catheterization is to identify the sources of pulmonary blood flow; the presence, size, and confluence of the central pulmonary arteries and their branches in the lungs; areas of stenosis in the lobar or segmental branches; and the origin and course of the MAPCAs and their connections to the true pulmonary arteries. In particular it should be emphasized the key role of the pulmonary vein wedge injection for the demonstration of native pulmonary arteries not detectable with other methods and its consequent central role in the surgical planning of this peculiar disease. In late referrals, which are common, especially in humanitarian cases, cardiac magnetic resonance (CMR) imaging now plays an important role in the diagnosis and surgical planning of patients with PA/VSD/MAPCAs. In addition, CT scan and CMR are the main sources of advanced 3D technology that we are increasingly using in clinical practice.CT is a reliable panoramic tomography modality for less invasive assessment of comprehensive cardiothoracic anatomy in patients with PA/VSD/MAPCAs ,4,5,6,7.CMR imaging provides also functional information for surgical decision making in patients with PA/VSD/MAPCAs. In our practice, CMR is a particularly useful adjunct to cardiac catheterization, either in late referrals or in staging when it is critical to assess total pulmonary blood flow and Qp:Qs ratio in view of possible complete delayed repair of the disease. Indeed, in this disease, systemic blood flow (Qs) can be measured as the addition of superior venous caval flow and descending aortic flow . Pulmonary blood flow (Qp) can be measured either as total pulmonary venous return ,9,10 or,(1)Acquisition of CT images;(2)3D image segmentation using dedicated 3D medical software;(3)Processing and editing of the virtual three-dimensional anatomical model.3D technology in cardiac surgery is now a consolidated clinical practice that has proven over the years that it can improve the surgical approach in complex clinical cases . In our Virtual models allow the surgeon to view and navigate the screen using a mouse, trackball, or remote control and can be used for surgical planning both preoperatively and intraoperatively. They allow the spatial relationship of MAPCAs to the aorta, airways, esophagus, and pulmonary veins to be identified. In addition, they allow determination of the exact origin and course of the collaterals in relation to the main bronchi and their branches and precise surgical planning of unifocalization preoperatively. Such preoperative planning can shorten surgical time and lead to improved clinical outcomes for the patient.The goals of surgical treatment are to achieve a single confluence of all sources of pulmonary blood flow  and to complete the repair by closing the VSD and creating a connection between the RV and pulmonary artery (PA). Originally, these aims were pursued in multiple stages over years , but nowPulmonary artery rehabilitation aimed at inducing native pulmonary artery growth was the first surgical treatment described for PA/VSD/MAPCAs. Gates-Laks central shunt  is probaOur current technique of choice for rehabilitation is the central shunt. We perform rehabilitation not only in patients with small confluent branch pulmonary arteries with normal arborization and dual-supply collaterals, but also in patients with prevalent nonexclusive distribution of native pulmonary arteries to the lungs see , in whomThe unifocalization technique, particularly in single-stage constitutes the approach of choice advocated by the Stanford group . Access 2/m2) [Our institutional approach for PA/VSD/MAPCAs is similar to that of the Stanford group. Pulmonary arterial rehabilitation is performed in all patients with confluent hypoplastic   but domiUnifocalization and rehabilitation focus on mobilization of collateral arteries and growth of native pulmonary vessels, respectively. Regardless of the strategy, the results have altered the natural history of the disease, with a complete cure rate of approximately 80% and low early and late mortality. In our experience to date, the ability to achieve definitive intracardiac repair is the critical factor for improved survival and adequate systolic RV performance at midterm follow-up . Patient−1 · m−2 is pumped into the reconstructed pulmonary bed and the mean pulmonary artery pressure (mPAP) is simultaneously recorded. An mPAP value of 30 mm Hg or less is selected for VSD closure, predicting adequate postoperative RV pressure. On the other hand, if mPAP rises above 30 mm Hg during the incremental steps of the flow study, the test is terminated, intracardiac repair is not performed and either a RV to PA conduit or a central shunt is placed based on individual patient assessment.The use of the intraoperative flow study as a functional measure of pulmonary vascular performance and suitability for VSD closure was first reported by Reddy and colleagues . In Octo2 because excessive priming of the pump is required and the ability of the pump oxygenator to maintain adequate both systemic and pulmonary blood flow is compromised. Late presenting humanitarian referrals encompassing more than 1 m2 of body surface area are subject to preoperative CMR imaging with the Qp:Qs ratio calculation and VSD closure decided accordingly if the Qp:Qs value exceeds 1.5:1.Proper performance of an intraoperative flow study can be problematic in patients with a body surface area greater than 1 mAt our institution, patients who did not receive VSD closure in the first instance are re-evaluated, also on the basis of the individual clinical condition, 6–12 months after surgery by cardiac catheterization, possibly associated with CMR. Intracardiac repair is indicated in the presence of Qp:Qs greater than 1.5, if their source of pulmonary blood flow is an RV to PA connection, or in the presence of Qp:Qs greater than 0.8 and mPAP less than 25 mmHg, if their source of pulmonary blood flow is a systemic-to-pulmonary shunt.p = 0.001), and is close to 100% in recent years. Prior to 2005, mortality was influenced by 22q11 deletion syndrome , whereas in recent years it no longer played a significant role . Based on a recent analysis, the overall rate of complete intracardiac repair in our series was approximately 83% for all patients who underwent unifocalization, either primarily or after rehabilitation procedures [Based on the above considerations and previously reported experience , from Jaocedures ,26. SurvPatient # 1. An 8 months/7.6 kg male with PA/VSD/MAPCAs  and confluent but hypoplastic intrapericardial pulmonary arteries underwent pulmonary artery rehabilitation and subsequent unifocalization with a central shunt. Patient # 2. A 7-year-old/15.8 kg  male underwent one-stage repair by unifocalization of all collaterals, reconstruction of the new pulmonary confluence, and VSD closure (intraoperative flow-study pressure of 20 mm Hg). The modern approach to PA/VSD/MAPCAs is the synthesis of decades of experience of the world’s leading centers in the treatment of this disease. The experience gained at our institution confirms that a structured approach to the treatment of this complex lesion is the key to achieve optimal results. In particular, over the course of the years we have demonstrated how staged and single-stage approaches should not be considered separate philosophies, but should be used as part of an integrated approach, based on rigorous patient selection. In this sense, both rehabilitation and unifocalization strategies, possibly used in sequence where feasible, play a fundamental role. From this perspective, modern diagnostic methods and 3D technology are an important tool for preoperative diagnosis and surgical planning. The ultimate goal is to achieve definitive intracardiac repair which has proved to be the main determinant of both improved survival and adequate RV systolic performance during mid-term follow-up.


This study was to investigate the correlation between glycated haemoglobin (HbA1c) level, cardiac function, and prognosis in patients with diabetes mellitus combined with myocardial infarction.  Ninety-three patients with type 2 diabetes mellitus combined with acute myocardial infarction who were hospitalized and treated in our hospital from January 2021 to June 2021 were recruited for prospective analysis and equally divided into group A (HbA1c < 6.5%), group B (6.5% ≤ HbA1c ≤ 8.5%), and group C (HbA1c > 8.5%) using the random number table method, with 31 patients in each group. General data of patients were collected on admission and blood glucose and cardiac function indexes were measured; the incidence of myocardial infarction and death during the follow-up period was recorded at 6 months after discharge. P < 0.05). There were statistically significant differences in plasma levels of N-terminal probrain natriuretic peptide (NT-proBNP) and uric acid (UA), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and cardiac function classification of the New York Heart Association (NYHA) among the three groups (P < 0.05). By statistical analysis, the HbA1c level was positively correlated with FBG, NT-proBNP, UA, LVEDD, LVESD, and NYHA grades but negatively correlated with LVEF (P < 0.05). The incidence rate of myocardial infarction and mortality was significantly higher in group C than in groups A and B (P < 0.05).  There was a significant difference in blood glucose (FBG) and HbA1c levels at fasting between the three groups ( HbA1c level in patients with diabetes mellitus combined with myocardial infarction is closely related to the degree of cardiac function damage. Glycated haemoglobin levels are associated with the development of cardiac insufficiency in patients with acute myocardial infarction; glycated haemoglobin is also an independent predictor of major adverse cardiovascular events. Reasonable and effective blood glucose control is of great significance to the prognosis of patients. Acute myocardial infarction is a common cardiovascular disease that could be life-threatening and significantly reduce the quality of life of patients. According to some literatures, the amount of people suffering from cardiovascular diseases in China reaches approximately 230 million, and there is epidemiological data indicating that one cardiovascular disease death occurs every 12 seconds in China. Acute heart attacks are common and prevalent in emergency departments, with rapid onset and progression, and could be fatal if not treated promptly and effectively . An addiGlycated haemoglobin (HbA1c) is an essential criterion for evaluating long-term blood glucose control in clinical practice . HbA1c iIn this study, 93 patients with type 2 diabetes mellitus combined with acute myocardial infarction admitted to our hospital from January 2021 to June 2021 were equally enrolled and divided into group A (HbA1c < 6.5%), group B (6.5% ≤ HbA1c ≤ 8.5%), and group C (HbA1c > 8.5%), reflecting the different levels of blood glucose control of the patients. A prospective analysis was conducted on the incidence of recurrent myocardial infarction and death and the correlation between HbA1c level with cardiac function and prognosis. The results are reported as follows.A total of 93 patients with type 2 diabetes mellitus combined with acute myocardial infarction who were hospitalized and treated in our hospital from January 2021 to June 2021 were recruited for prospective analysis and equally divided into group A (HbA1c < 6.5%), group B (6.5% ≤ HbA1c ≤ 8.5%), and group C (HbA1c > 8.5%) using the random number table method, with 31 patients in each group.With a sample size of 31 subjects observed with A, B, and C, the trial will have more than 90% power to detect a difference between A, B, and C in the proportion of subjects with a myocardial infarction and death greater than 10%, given that the probabilities to achieve this myocardial infarction and death are 10% for A and 14% for B.The trial was conducted according to Good Clinical Practice guidelines developed by the International Council for Harmonisation and in compliance with the trial protocol. The protocol was approved by the institutional review boards or independent ethics committees at each site . All patients provided written informed consent per Declaration of Helsinki principles. An independent data monitoring committee monitored safety and efficacy data.Patients aged 18-80 yearsPatients meeting the diagnostic criteria of type 2 diabetes onset time < 12 hPatients with a diagnosis of ST-segment elevation myocardial infarction  and onsePatients who have been on regular hypoglycaemic therapy for more than 6 monthsleads ≥ 2 mm or within 18 hours of onset, with evidence of ongoing ischaemia or haemodynamic instabilityPatients with typical chest pain symptoms lasting more than 30 minutes and ST-segment elevation in two adjacent Patients with serious infectious diseases or autoimmune diseases and traumaPatients with malignant tumorsPatients with diabetic complications, such as diabetic foot and diabetic ketoacidosisPatients with old myocardial infarction or coronary artery caused by various reasons and angiography failurePatients with acute liver and kidney insufficiencyPregnant or lactating womenGeneral information of patients such as age, gender, height, weight, hypertension, hyperlipidemia, history of cardiovascular disease, hypoglycaemic therapy, and infarction site was collected at enrollment. Patients had their venous blood drawn during fasting and centrifuged at 3000 r/min for 20 min; then, the HbA1c level was determined by cationic high-performance liquid chromatography. The kit was purchased from Shanghai Yudole Biotechnology Co., Ltd. Fasting blood-glucose (FBG) levels were determined by enzyme-linked immunosorbent assay. The kit was purchased from Shanghai Jichun Industrial Co., Ltd. (Cat. No. JCSW2609).Fasting venous blood was drawn from patients and centrifuged at 3000 r/min for 20 min to separate the serum, then plasma, and the level of N-terminal probrain natriuretic peptide (NT-proBNP) in the plasma was determined by enzyme-linked immunosorbent assay. The kit was purchased from Wuhan Fein Biotechnology Co., Ltd. (Cat. No. EH0350), and an automatic biochemical analyser  was used to measure serum uric acid (UA) levels. The left ventricular end diastolic diameter (LVEDD), left ventricular end systolic volume (LVESV), and left ventricular ejection fraction (LVEF) were measured by echocardiography. The cardiac cycle was averaged, and the instrument used the cardiovascular ultrasound diagnostic apparatus (iE33 type) produced by Philips. The New York Heart Association (NYHA) was used to evaluate the cardiac function of patients.Grade I: the patient's general activities were basically unrestricted. Grade II: patients were asymptomatic at rest, but physical activity was slightly restricted. Grade III: the patient's physical activity was markedly restricted, and activity less than normal could cause symptoms of palpitations, dyspnea, and angina pectoris. Grade IV: patients had inability to perform any physical activity, and the above symptoms could occur at rest.The patients were followed up monthly by outpatient and telephone for 6 months after discharge, and the occurrence of myocardial infarction and death was recorded during the follow-up period.b is unbiased and normally distributed.If the parameter beta is either a difference of means, a log odds ratio, or a log hazard ratio, then it is reasonable to assume that q test for pairwise comparison. The enumeration data were expressed as [n(%)], the total number of cases was ≥40, the minimum theoretical frequency > 5, and the chi-square uncorrected method was used. Bivariate correlations conforming to a normal distribution were analysed using Pearson analysis, and those not conforming to a normal distribution were analysed using Spearman's rank correlation. P < 0.05 indicated that the difference is statistically significant.SPSS 20.0 software was used for statistical analysis of the data. The measurement data conformed to a normal distribution and were expressed as P > 0.05)  .P < 0.05) (There were significant differences in FBG and HbA1c levels between the three groups of patients ( < 0.05) .P < 0.05)  .P < 0.05)  .P < 0.05)  .Acute myocardial infarction is typically divided into ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction , while SGlucose management is the primary goal of patients with diabetes . Not onlAccording to the latest ESC guidelines, NT-proBNP has been adopted as a marker for evaluation of heart failure and as an essential indicator of cardiac function and prognosis in patients with acute myocardial infarction . UA is aIn this study, the levels of NT-proBNP and UA in blood, cardiac color Doppler ultrasound parameters, and NYHA classification were used to evaluate the cardiac function of three groups of patients. And the composition ratio of NYHA grades III and IV was significantly higher than that of HbA1c < 6.5%, and the LVEF was lower than HbA1c < 6.5%, which consistent with the results of previous research . In addiCertain factors may play a key role in the association between HbA1c levels and poor prognosis. Increased HbA1c levels are associated with certain baseline characteristics that elevate the risk of cardiovascular disease, which explains part of the increase in long-term mortality. Additionally, there is a robust association between overt diabetes and adverse cardiovascular outcomes, and it is conceivable that part of the association between poor long-term glycaemic control and outcomes has the same complex mechanisms as the association between overt diabetes and cardiovascular outcomes. Indeed, it is well established that the risk of developing coronary artery disease is not limited to diabetics but exists in other states of impaired fasting glucose, impaired glucose tolerance, and insulin resistance. Reasonable and effective blood glucose control is an important means of reducing cardiovascular complications in patients. In terms of prognosis, the incidence of remyocardial infarction and mortality of patients in group C was significantly higher than those in the groups A and B, further indicating the prognostic importance of glycaemic control on patients' prognosis.As the proportion of people with chronic poor glycaemic control and consequent cardiovascular disease is likely to increase in the next decade, more appropriate treatment should be recommended for this population. According to the European guidelines for the management of diabetes, prediabetes, and cardiovascular disease, it is recommended that people at high risk of type 2 diabetes should undergo lifestyle modifications. If necessary, medication should be administered to reduce their risk of developing overt hyperglycaemia and type 2 diabetes and, in particular, to prevent or slow down the onset of cardiovascular disease. While this approach has yet to be proven for slowing the course of diabetes, in patients with diabetes or mildly abnormal blood glucose levels, the overall increased risk of cardiovascular disease cannot be explained by abnormalities in blood glucose or HbA1c alone. However, considering that lowering HbA1c levels may have an improved prognosis, it is still possible to encourage our patients to make lifestyle modifications or take medication to prevent or slow down the onset of cardiovascular disease. There are still some limitations to our study. Firstly, this study was conducted in a single centre and is subject to a large margin of error and chance due to the small sample size, limited follow-up time, and small number of cases followed up to the clinical endpoint. Furthermore, as glycated haemoglobin levels were only measured once during hospitalization, it was not feasible to assess the change in HbA1c levels after active treatment and its correlation with clinical events.To sum up, the HbA1c levels in diabetic patients combined with myocardial infarction are closely related to the degree of cardiac impairment, and reasonable and effective glycaemic control is of great significance to the prognosis of patients. Considering the possible role of lowering HbA1c levels in improving the prognosis of STEMI, patients with elevated HbA1c should be advised to make lifestyle modifications or take medication to prevent or slow down adverse cardiovascular events. This requires the consideration of clinicians.