During the last 30 years, we have assisted to a great implementation in anticancer treatment with a subsequent increase of cancer survivors and decreased mortality. This has led to an ongoing interest about the possible therapy-related side-effects and their management to better guide patients therapy and surveillance in the chronic and long-term setting. As a consequence cardio-oncology was born, involving several different specialties, among which radiology plays a relevant role. Till the end of August 2022, when European Society of Cardiology (ESC) developed the first guidelines on cardio-oncology, no general indications existed to guide diagnosis and treatment of cancer therapy-related cardiovascular toxicity (CTR-CVT). They defined multimodality imaging role in primary and secondary prevention strategies, cancer treatment surveillance and early CTR-CVT identification and management.Cardiac computed tomography angiography (CCTA) has acquired a central role in coronary assessment, as far as coronary artery disease (CAD) exclusion is concerned; but on the side of this well-known application, it also started to be considered in left ventricular function evaluation, interstitial fibrosis quantification and cardiac perfusion studies.Cardiac magnetic resonance (CMR), instead, has been acknowledged as the gold standard alternative to trans-thoracic echocardiography (TTE) poor acoustic window in quantification of heart function and strain modifications, as well as pre- and post-contrast tissue characterization by means of T1-T2 mapping, early Gadolinium enhancement (EGE), late Gadolinium enhancement (LGE) and extracellular volume (ECV) evaluation.Our review is intended to provide a focus on the actual role of CMR and CCTA in the setting of a better understanding of cardiotoxicity and to draw some possible future directions of cardiac imaging in this field, starting from the recently published ESC guidelines. This has led to an ongoing interest about the possible therapy-related side effects and their management to better guide patients therapy and surveillance in the chronic and long-term setting. For this purpose, a new discipline was born, namely, cardio-oncology, involving several different specialties, among which radiology plays a relevant role in both cardiotoxicity identification and follow-up through multimodality imaging.During the last 30 years, we have assisted to a great implementation in anticancer treatment with a subsequent huge increase of cancer survivors. Nowadays, the consensus statement of the International Cardio-Oncology Society (IC-OS) has overcome these issues with a specific definition of cancer therapy-related cardiac dysfunction (CTRCD) as cardiomyopathy, heart failure (HF), myocarditis, vascular toxicity, hypertension (HTN), cardiac arrhythmias, and corrected QT interval prolongation induced by anticancer therapy. For CTR-CVT-induced pericardial and valvular heart diseases, definitions are the same used for the general population.Over the past decades, different definitions have been used to describe cancer therapy-related cardiovascular toxicity (CTR-CVT), generating confusion and misdiagnosis. Among them, the most common is the one given by the American Society of Echocardiography, describing cancer treatment-related cardiac dysfunction as a decrease in left ventricular ejection fraction (LVEF) of >10% to a value <53%.Till the end of August 2022, no international guidelines have existed to guide diagnosis and therapy of CTR-CVT, when the first European Society of Cardiology (ESC) guidelines on cardio-oncology were developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and IC-OS.As already stated, multimodality imaging plays a central role in primary and secondary prevention strategies, cancer treatment surveillance and early CTR-CVT identification and management. Our review will mainly focus on the actual role of cardiac magnetic resonance (CMR) and cardiac computed tomography angiography (CCTA) in the setting of a better understanding of cardiotoxicity predictive factors, early diagnosis, treatment, and follow-up. We will briefly analyze them from a clinical and pathophysiological point of view.The most common clinical manifestations of CRT-CVT are acute and chronic HF, myocardial ischemia, electrophysiological disturbances, HTN, and vessel thromboembolism. Cyclophosphamide and ifosfamide are thought to cause direct endothelial injury by means of extravasation of toxic metabolites leading to cardiomyocytes damage, interstitial damage, and hemorrhage. Bevacizumab has been demonstrated to induce HF via uncontrolled HTN and inhibition of Vascular Endothelial Growth Factor (VEGF), while Trastuzumab interferes with normal cardiomyocytes growth by inhibiting their epidermal growth factor receptor 2 (Erb2).HF is mostly induced by the administration of anthracyclines, cyclophosphamide, ifosfamide, bevacizumab, trastuzumab, and imatinib. From the pathophysiological point of view, free radical formation is recognized as the main mechanism of cardiotoxicity in anthracyclines treatment. From the pathophysiological point of view, coronary artery thrombosis, arteritis, and vasospasms are proposed as the main causative mechanisms of ischemia in antimetabolites and antimicrotubules therapy . Bevacizumab, instead, seems to cause myocardial ischemia through its anti-VEGF mechanism.Myocardial ischemia is commonly diagnosed in cancer patients, particularly in those treated with antimetabolites, antimicrotubules, and monoclonal antibody-based tyrosine kinase inhibitors. They can be caused by anti-cancer-induced fibrosis and radiation therapy, directly affecting the heart conduction system. Concerning bradycardia, paclitaxel is considered as the main causative agent among chemotherapeutic drugs via its direct effect on Purkinje fibers or extracardiac autonomic control. QT prolongation causative mechanisms remain unknown and are still quite rare, especially related to small molecule tyrosine kinase inhibitors.Bradycardia and QT prolongation are the main electrophysiological disturbances found in CRT-CVT. Studies have shown that it may be related to the VEGF inhibition, decreasing nitric oxide production in arterioles leading to increased vasoconstriction and peripheral vascular resistance.HTN is the most frequent comorbid condition reported in cancer patients. Cisplatin, for example, induces platelet activation and aggregation interfering with monocytes pro-coagulant activity and elevating von-Willebrand factor levels.Cancer patients commonly stay in a pro-thrombotic state, which is in some cases worsened by specific anticancer treatment, like alkylating agents and angiogenesis inhibitors, frequently resulting into vessels’ thromboembolism.Clinical manifestations for chemotherapeutic agents are reported in In the last decades, immunotherapy has become of common use in the treatment of various diseases, such as non-small cell lung cancer, renal cell carcinoma, and both Hodgkin and non-Hodgkin lymphoma. Checkpoint inhibitor immunotherapy  is immunomodulatory antibodies that are used to enhance the immune system. These agents have substantially improved the prognosis for patients with advanced malignancy.Despite clinical benefit, ICI are associated with a broad spectrum of side effects that are caused mainly by their activity on the immune system: these side effects are known as immune-related adverse events (IrAEs) with various manifestations including cardiotoxicity in up to 1% of patients.Its manifestation typically includes hypotension, arrhythmia, and left ventricular dysfunction, typically in the setting of cytokine release syndrome. Clinical features are extremely variable, in terms of disease onset and severity of manifestations, ranging from fatal myocarditis to transient myocardial edema. Median interval time from first treatment to disease presentation is typically 1–2 months, but cases of delayed onset have been reported up to one year.Of significant interest for the role of advanced imaging is the occurrence of acute ICI induced myocarditis, whose incidence is documented around 0.04–1.14% and which has been associated with a worsening of mortality.The underlying pathophysiology for ICI-associated myocarditis is not yet fully understood.One possible mechanism is that T cells could target an antigen shared by both the tumor and the heart. Preclinical studies in mouse models have demonstrated that PD-1 protects the heart against T-cell-mediated inflammation and that PD-1-deficient mice develop myocarditis. Similarly, CTLA-4-deficient mice also developed autoimmune myocarditis with infiltration of CD4+ and CD8+ T lymphocytes in the myocardium. Deletion of the CTLA-4 and PD-1 axis led to autoimmune myocarditis, which suggests that PD-1/PDL1 and CTLA-4 play important roles in limiting T-cell-mediated autoimmune myocarditis.Other mechanisms underlying ICI-mediated cardiotoxicity include pericardial inflammation by ICI-stimulated cytotoxic T-cells and myocardial ischemia. Indeed, ICI-associated inflammation may act on atherosclerotic coronary plaques and trigger fibrous cap rupture, leading to acute myocardial infarction. A second possible underlying mechanism of ICI-associated acute myocardial ischemia is coronary spasm causing ST elevation secondary to PD-1 inhibitor (pembrolizumab) treatment. The exact mechanism of coronary spasm remains unclear but may be related to systemic inflammatory response syndrome. A third explanation for ICI-related acute MI is the direct activation of T-cell-mediated coronary vasculitis in the absence of atherosclerosis. An indirect effect of ICIs on the coronary vasculature via a sudden release of large amounts of catecholamine from the adrenal glands or postganglionic sympathetic nerves in the heart, could result in catecholamine-mediated myocardial stunning (Tako-tsubo syndrome).Almost all cardiovascular adverse reactions, especially myocarditis, are firstly clinically suspected with cardiac enzymes and ECG alteration, but most of the evidence suggest CV imaging is requested to perform an accurate diagnosis. For this purpose, trans-thoracic echocardiography (TTE) and CMR are interchangeably indicated by 2022 ESC guidelines, but a specific and exclusive role of CMR could be postulated on the basis of modified Lake Louise Criteria accuracy., aiming at giving all the healthcare professionals the instruments to take care of oncologic patients before, during and after cancer treatment as far as the cardiovascular system is concerned. They represent a consensus on definition, diagnosis, treatment, and prevention of CTR-CVT. Guidelines include clear indications regarding the role and the appropriate use of different imaging modalities in various clinical scenarios, namely, cardiovascular toxicity risk stratification before anticancer therapy and cardiovascular surveillance during treatment  by means of coronary calcium score quantification and to detect intracardiac masses. Accurate imaging techniques are requested for this aim, like 3D echocardiography or CMR. Choice of favourite imaging technique depends on the local availability and expertise; no strict indication favors TTE over CMR at this point but the same imaging modality is recommended over the entire follow-up to allow a precise comparison. TTE is still recommended for left ventricular function and GLS assessment to detect cardiac dysfunction, but in case of poor image quality or non-diagnostic TTE, CMR has to be considered  like HTN, HF, acute coronary syndromes, arrhythmias, pulmonary HTN, and venous thromboembolism. Among them, HF with preserved ejection fraction is frequently associated with cardiac amyloidosis in MM but also to PI therapy; in this setting, a baseline CMR before treatment initiation followed by TTE every three cycles of PI is the commonly accepted surveillance protocol.A specific indication for CMR exists as far as cardiovascular surveillance for multiple myeloma (MM) targeted therapy is concerned. Proteasome inhibitors (PI) – bortezomib, carfilzomib, and ixazomib – have become a mainstay for MM treatment.CCTA is a widely available imaging technique for the evaluation of coronary anatomy and pathology, which can be exploited in the setting of secondary prevention, as far as CAD rule-out is concerned. Despite this knowledge, while clear recommendation exists to rule out CAD in case of first evidence of HF with reduced ejection fraction, no guidelines recommend a pre-treatment evaluation of CAD. Due to its high sensitivity in excluding CAD, CCTA is now widely used to exclude coronary stenosis in patients with exposure to cardiotoxic anticancer treatment and newly developed reduced LVEF. Non-contrast CT provides information about calcium burden within the coronary arteries as a reliable predictor of cardiovascular risk; it can be used to drive cardio-protective therapy before and during cytotoxic anticancer treatment like anthracyclines as proposed by the society of Cardiovascular Computed Tomography and the Society of Thoracic Radiology.Pre-existing CAD has been demonstrated to contribute to an increased risk of cardiovascular toxicity in patients undergoing anti-cancer treatment.An example of CAD rule-out by CCTA is shown in ) No strong evidences exist about CCTA role in cardiac function assessment and tissue characterization, where CMR is still superior. As far as tissue characterization is concerned, which is the main early markers of cardiotoxicity, future CCTA technology, like Photon Counting CT, may lead to CCTA as a competitive imaging modality in CTR-CVT early recognition and prevention. Radiation exposure issues still represent a major limitation to CCTA use, although new multidetector machine already maximally reduce dose.As already stated, CCTA value in Cardioncology field is nowadays confined to CAD rule-out in case of reduced LVEF, playing a limited role in all the other possible clinical scenarios, according to ESC 2022 guidelines. or more than 10% without other recognized causes.The spectrum of tissue abnormalities characterizing myocardial toxic effects of chemotherapy ranges from tissue edema and necrosis to the development of focal replacement and interstitial fibrosis. CMR has also been recognized as a significant prognostic tool in various clinical settings, which can be easily extended to the field of cardio-oncology.  and  while increase in T2 relaxation time is associated with acute myocardial edema, being a water-sensitive process. Generally speaking, cardiotoxic drug exposure has been associated with an increase in both native T1 and T2 relaxation time  and/or LGE is a hallmark of underlying pathologic processes like inflammation, edema, and myocardial fibrosis A limited tolerability of the exam does not allow to perform it in claustrophobic or patients unable to maintain apnea. Despite all the possible application of CMR in function assessment, tissue characterization and strain evaluation, still limited robust evidences exist about their changes in Cardiotoxicity, to allow for accurate diagnosis and prevention of CTR-CVT.Major CMR limitations derive from its costs and exam tolerability by patients, for which reason TTE still represents the first imaging modality of choice in Cardioncology according to ESC 2022 guidelines.Despite its exclusively approved role in CAD rule-out, literature evidence suggests possible CCTA use for left ventricular function evaluation, cardiac perfusion studies, and tissue characterization. and CMR quantification of late gadolinium enhancement was validated as a gold standard non-invasive method for the identification of focal myocardial fibrosis in the setting of ischemic and non-ischemic cardiomyopathy. In the last 20 years also CCTA has been used for the assessment of cardiac fibrosis by means of ECV quantification. The same imaging protocol as CMR has been adopted with a non-contrast low-dose ECG-gated CCTA acquisition followed by multiple imaging after contrast administration at a given time delay, usually around 10 min. A good correlation was found between CCTA findings and both CMR ECV and histological fibrosis also in cancer patients undergoing anthracycline chemotherapy regimens. CCTA-based ECV calculation has also some drawbacks, namely, the increased radiation dose delivered to the patients along with difficulty in image registration and segmentation. These aspects seem to be possibly overcome by the introduction of dual source energy CCT: reduced radiation dose through the elimination of pre-contrast images, improvement of image quality by beam hardening artefact reduction, and less wrong image registration.Multiple studies demonstrated extracellular volume (ECV) increase in patients treated with cardiotoxic chemotherapy compared to matched control population,From a functional perspective, subtle early tissue changes following chemotherapy may induce regional wall motion impairments that can be detected using advanced strain CMR-based imaging. This technique is based on the principle of tracking tissue voxel motion using standard steady-state free precession sequences.In the last years, left ventricular GLS merged as a more accurate index of left ventricular dysfunction, as demonstrated by the SUCCOR (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes) international multicenter prospective randomized controlled trial. Echocardiographic GLS-guided cardioprotective therapy better prevents chemotherapy-induced cardiotoxicity in comparison with LVEF in a high-risk population receiving cardiotoxic chemotherapy. A prospective study conducted by Drafts et al demonstrated an early subclinical deterioration in global circumferential strain (GCS) in patients receiving low-moderate dose of anthracyclines along with subclinical decline of LVEF, proving GCS as an early predictor of cardiotoxicity. An example of the utility of CMR longitudinal circumferential and radial strain as an early marker of cardio-toxicity is shown in  Their evaluation is recommended in all patients screened before cardiotoxic cancer treatment initiation to stratify CTR-CVT risk and to identify significant changes during treatment.CMR studies have proposed myocardial global longitudinal circumferential and radial strain to describe LV dysfunction, also in patients who have undergone anthracyclines and trastuzumab therapy.Among the different values of CMR strain, GLS and GCS are the most used because of less technical limitations with respect to global radial strain (GRS). Coherently, several studies have also demonstrated a significant decrease in left ventricular mass after anthracycline therapy. De Souza et al introduced a new method of measuring cardiomyocytes size with CMR, the intracellular water lifetime. It demonstrated a decrease in left ventricular mass due to cardiomyocytes atrophy in females treated with anthracyclines for breast cancer. Another study found an association between left ventricular mass decline, increased risk of cardiac events and HF symptoms more than LVEF decline.In the specific case of anthracyclines, decline in LVEF and deterioration of strain  values has been postulated to be associated with an atrophic remodeling of myocardium induced by DNA oxidative damage.Among all possible myocardial inflammation, ICI-related myocarditis represents a specific pathological entity from a clinical, radiological, and histopathological point of view. Differently from non-ICI myocarditis, less than 50% of cases present with a decreased ventricular function and relevant LGE.Most of patients developing ICI myocarditis show atypical patterns of LGE, without any association with pathology prognosis, meaning LGE approach is necessary but not sufficient for their evaluation.Quantitative parametric T1 and T2 mapping, as well ECV, seem to represent a real instrument to avoid underdiagnoses and overcome this inconsistency, in such a way to allow for a proper and prompt diagnosis of a pathology which brings a relevant mortality into the general population. demonstrate a better correlation between T1 and T2 mapping and both clinical and histological ICI-induced myocarditis characteristics. T1 mapping alterations are significantly correlated with symptom severity as well as to the histological specimen; even better and more significantly than T2 mapping, T1 mapping alteration seems to be correlated with the incidence of major cardiovascular adverse events.Recent studies, like the one of Paaladinesh et al,An example of ICI-induced myocarditis is shown in This opens to the possibility of designing specific CMR protocols, centered on quantitative parametric mapping, with a diagnostic and prognostic role from the pre-subclinical stages to the full-blown pathology. we propose a novel baseline risk assessment flowchart for patient’s candidate to potential cardiotoxic therapy, according to our Institution’s clinical routine (Despite the recently published ESC guidelines, on the basis of an accurate review of the new risk assessment tools from Cardioncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardioncology Society, routine .A baseline Calcium Score quantification on a non-contrast ECG-gated chest CT performed during the cancer staging phase is strongly suggested according to the strong evidence correlation between coronary calcification and increased risk for a major adverse cardiac event.Regardless of these solid and consistent scientific bases, current CMR role is apparently limited to patients with poor acoustic TTE window, hypertrophic cardiomyopathy, and PI-induced MM, but its potential goes far beyond these applications. CMR should be considered as a first-line imaging at least in patients at high/very high risk to develop CTR-CVT, in order to be able to precisely estimate ventricular volumes and function but also to perform tissue characterization and identify subclinical changes by means of mapping, LGE sequences and ECV evaluation. Whenever CMR results normal, patients may be followed-up clinically and according to the standard guideline; in the case of any pathological abnormalities, following investigations should be performed with CMR for the sake of reproducibility and precision.While TTE is still recognized as the favourite imaging technique for baseline risk stratification, guidelines opened a new potential window for CMR application, but the pathway is still ongoing.ESC 2022 and all other possible applications for functional evaluation, GLS, LGE, and ECV quantification are not even mentioned for its poor availability and standardization. The main potential strength of the introduction of CCTA in cardiovascular toxicity risk assessment and evaluation during therapy is that oncologic patients routinely undergo computed tomography exams for cancer staging, monitoring, and follow-up. This would mean maximizing the usefulness of an exam which cannot be bypassed in oncologic patients and adapting it to a double use: the purely oncologic staging and follow-up but also the possible complete cardiac evaluation in specific subsets of the population at risk of CTR-CVT.CCTA use in this setting still remains limited to CAD exclusion in low-intermediate risk patients More evidences are needed about the possible clinical role of the above-mentioned imaging findings in guiding multifactorial therapeutic pathways and decision.Application of advanced cardiac imaging in oncology is an open field for research.


Although Takotsubo syndrome (TS) has been long recognized, it is now more frequently identified as a cause of stress-induced cardiac injury since its first description in the 1990s. While most cases are transient, many patients can have acute and long-term effects including persistent or worsening heart failure, arrhythmia, cardiac thrombi, outflow tract obstruction, ventricular wall rupture, and cardiogenic shock. Medical optimization is necessary to prevent cardiac remodeling and disease recurrence and manage associated heart failure. The choice of medications may vary from patient to patient based on the inciting factor or the most probable cause. Anticoagulation can be added for a small period of time if there is a concern for thrombus formation from akinesia/dyskinesia. Most patients achieve early recovery and resolution of symptoms and those with persistent manifestations can be managed medically. Takotsubo syndrome (TS) is a cardiac disorder that can cause transient wall motion abnormalities (WMA), and hypokinesia/dyskinesia/akinesia of segments of the heart, which determines the “type” of Takotsubo cardiomyopathy  . The claA 58-year-old female presented due to a first-time episode of dull retrosternal chest pain, tightness, and pressure with exertion and at rest, rated 10/10 in intensity, radiating to the back in the left interscapular region since that morning lasting about 1.5 hours. She endorsed profuse diaphoresis, dyspnea, lightheadedness, and palpitations but denied syncope and loss of consciousness. She had experienced a similar episode many years ago but had never consulted a cardiologist. She was compliant with her medications including losartan 25 mg daily and levothyroxine 88 mcg daily. She denied vaping or alcohol and illicit drug use. Her smoking status was unknown (she possibly smoked a few cigarettes daily for 10 years). The physical exam was unremarkable except for mild chest tenderness.The patient's past medical and surgical history included hypertension, hyperlipidemia, hypothyroidism, and meningioma s/p craniotomy ~8 years ago. She denied any history of acute coronary syndrome/myocardial infarction (ACS/MI), congestive heart failure (CHF), heart murmur, rheumatic fever, arrhythmia, heart block, and anxiety. In pertinent family history, her father had experienced a stroke. Differential diagnoses included non-ST-elevation myocardial infarction (NSTEMI), pulmonary embolism, aortic dissection, pneumothorax, pericarditis, pericardial tamponade, esophageal rupture, pneumonia, pleurisy, gastroesophageal reflux disease (GERD), and musculoskeletal chest pain. Her heart score was 5. Chest X-ray was unremarkable except for mild cephalization Figure .Vitals showed a temperature of 97.7 °F, a heart rate of 64 beats per minute, and a respiratory rate of 15 breaths per minute. Her blood pressure was 112/76 mmHg. Labs were significant for elevated ALT (~39), leukocytosis (~11.2K), low thyroid stimulating hormone (TSH)/free T4 (~0.182/0.61), and elevated triglycerides (~258). UDS, coagulation panel, electrolytes, D-dimer, and SARS tests were unremarkable. HS troponin trend was as follows: admission: 207→2794→1478→; day of cath: 573→2148→1974→; POD 1: 1199→712→642→; POD 2: 616→544. Figure The patient was given fluids, aspirin, and nitroglycerin and admitted to telemetry. Cardiology was consulted. The patient’s chest pain initially subsided with the above but recurred as dull chest pressure. She was otherwise hemodynamically stable. Troponin was elevated and repeat EKG showed T-wave inversions not present on the initial EKG Figures , 3. A fuThe patient was discharged in stable condition and advised to follow up with the cardiologist as an outpatient. She was discharged home on aspirin, atorvastatin, lisinopril, and metoprolol succinate. She was subsequently readmitted for orthopnea and midsternal, non-radiating, reproducible pleuritic chest pain. Her troponin remained elevated and was likely secondary to demand ischemia, periprocedural myocardial injury, and LV dysfunction. Repeat limited Echo showed EF of ~55% but with no significant WMA as seen on the previous Echo. Cardiologist readjusted her medications with the addition of isosorbide mononitrate, furosemide, and spironolactone to address LV failure and to reverse remodeling, given her symptomatic presentation although EF was preserved. The patient’s symptoms resolved and she was discharged when stable. She has not had any further ER visits or readmissions to this hospital since.Management of TS mainly involves supportive therapy. Approach to acute management can be based on the suspected underlying cause, although this is difficult to achieve as patients presenting are usually worked up for other diseases such as acute MI, and the diagnosis is not made until after catheterization and left ventriculogram. Therapy corresponding to pathophysiology would mean beta-blockers in suspected autonomic hyperactivity, nitrates or calcium channel blockers in coronary vasospasm, etc. . Heart fShort-course anticoagulation can be added especially if there is a concern for thrombus formation related to cardiac akinesia/dyskinesia with ballooning . PatientAlthough TS is seen as a benign transient condition, it can lead to many acute complications. Some of these complications include acute heart failure, LVOTO, RV involvement, mitral regurgitation, arrhythmias, cardiac thrombus formation, pericardial effusion, ventricular wall rupture, and cardiogenic shock. Depending on the clinical analysis, hemodynamic stability, Echo findings, suspected diagnosis, and underlying pathophysiology, therapy needs to be tailored to individual patients. Mortality usually occurs due to refractory shock or fatal arrhythmias such as ventricular fibrillation. Data on long-term prognosis is limited; while most patients recover within a few weeks, there have been reports on subsets of patients who experience persistent symptoms such as exertional dyspnea, palpitations, and angina. Beta-blockers can exacerbate bradyarrhythmia or AV blocks, and hence they need to be used with caution. Inotropic agents can help in cardiogenic shock but are contraindicated in LVOTO. Thus, medical optimization is important to prevent future recurrence and long-term complications of the disease.


Diabetic peripheral neuropathy (DPN) has been shown to be independently associated with cardiovascular events and mortality. This study aimed to evaluate changes in left ventricular (LV) microvascular perfusion and myocardial deformation in type 2 diabetes mellitus (T2DM) patients with and without DPN, as well as to investigate the association between myocardial perfusion and LV deformation.Between October 2015 and July 2022, one hundred and twenty-three T2DM patients without DPN, fifty-four patients with DPN and sixty age‑ and sex‑matched controls who underwent cardiovascular magnetic resonance imaging were retrospectively analyzed. LV myocardial perfusion parameters at rest, including upslope, time to maximum signal intensity (TTM), max signal intensity (max SI), and myocardial strains, including global radial, circumferential and longitudinal strain , were calculated and compared among the groups with One‑way analysis of variance. Univariable and multivariable linear regression analyses were performed to explore the independent factors influencing LV myocardial perfusion indices and LV strains in diabetes.The LV GLS, upslope and max SI were significantly deteriorated from controls, through patients without DPN, to patients with DPN . Compared with controls, TTM was increased and LV GRS and GCS were decreased in both patient groups . Multivariable regression analyses considering covariates showed that DPN was independently associated with reduced upslope, max SI and LV GLS . When the perfusion indices upslope and max SI were included in the multivariable analysis for LV deformation, DPN and upslope  were significantly associated with LV GLS.In patients with T2DM, there was more severe LV microvascular and myocardial dysfunction in patients with complicated DPN, and deteriorated subclinical LV systolic dysfunction was associated with impaired myocardial circulation. As one of the cardiovascular complications of diabetes, diabetic cardiomyopathy leads to an increased incidence of heart failure and mortality in the general population . DiabetiCardiovascular magnetic resonance (CMR) imaging has been increasingly used to comprehensively evaluate myocardial microcirculation as well as cardiac structure and function with high reproducibility. First-pass CMR imaging provides the ability to noninvasively evaluate myocardial perfusion during the transit of gadolinium and has been increasingly used in recent years to detect microvascular dysfunction , 9. The Therefore, this study aimed to quantitively evaluate myocardial microcirculation and LV function using CMR first-pass perfusion and CMR-FT technologies in T2DM patients with and without DPN, as well as to investigate the association between myocardial perfusion and LV strains.2); (4) other causes of peripheral neuropathy ; and (5) incomplete clinical record or poor CMR image quality that affecting LV measurements. Finally, one hundred seventy-seven T2DM patients, including 123 patients without DPN  and 54 patients with DPN , were eligible for this study. A detailed flow chart of the present study is presented in Fig. From October 2015 to July 2022, 558 T2DM patients who had undergone CMR examinations were initially screened. Patients were diagnosed with T2DM according to the diagnostic criteria of the American Diabetes Association guideline (2019) , and DPNThis study complied with the Declaration of Helsinki and was approved by the Biomedical Research Ethics Committee of our hospital. Written informed consent was waived due to the retrospective nature of the study.2 or 250 × 300 mm2, matrix size = 256 × 166 or 208 × 139). Twenty-five frames were reconstructed per breath-hold acquisition.CMR imaging was performed with a 3 T MRI imaging unit MAGNETOM Skrya or TrioTim . With subjects in the supine position, respiratory and electrocardiography gating were used throughout the scanning process. The short-axis cine images from apex to the base of the heart and long axis 4- and 2-chamber cine images were acquired with a balanced steady-state free precession sequence  and a long-axis 4-chamber image with inversion recovery-prepared echo-planar sequence  after intravenous injection of 0.2 mL/kg gadolinium contrast through the cubital vein at a rate of 2.5–3.0 mL/s, followed by 20 mL of saline. Then, late gadolinium enhancement (LGE) images in the entire LV short-axis stack and from the 2-, 3- and 4-chamber views were acquired to exclude patients with infarct LGE and identify patients with non-infarct LGE after 10–15 min of contrast administration by segmented-turbo-FLASH–phase-sensitive inversion recovery (PSIR) sequence .42, v.5.11.2; Circle Cardiovascular Imaging, Inc., Calgary, Canada) was utilized to analyze the CMR images by two radiologists with more than 5 years of experience in CMR who were blinded to the clinical data. First, the LV endo- and epicardial contours were semi-automatically delineated at end-diastole and end-systole on a stack of short-axis cine images, and then LV cardiac geometry and function were automatically calculated, including end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), LVEF and LV mass (LVM). LVM, LVEDV, LVESV, and LVSV were indexed to body surface area (BSA) and represented as LVMI, LVEDVI, LVESVI and LVSVI, respectively. The papillary muscles and moderator bands were excluded from LVM and included in LV volume. The LV remodeling index was calculated as the ratio of LV mass to LVEDV.The offline commercial software  tissue tracking module by the above software. The LV global radial (GRS), circumferential (GCS) and longitudinal (GLS) strain were obtained automatically  and nonnormal variables as the median (25–75% interquartile range). The differences among the three groups were assessed using one-way analysis of variance (ANOVA) with post hoc Bonferroni correction or Kruskal‒Wallis tests. The duration of T2DM and HbA1c levels were compared between the patient groups by Mann–Whitney U test. Categorical variables are expressed as numbers (percentages) and were compared using Fisher’s exact test or the chi-square test as appropriate. Univariable analysis was conducted to identify the variables related to LV microcirculation and deformation. Variables with a p value < 0.1 in univariable analysis as well as diabetes duration were included in multivariable linear regression analyses to determine the effects of imaging and clinical variables on myocardial circulation and cardiac systolic function in patients with T2DM. Diabetes duration was categorized as long (> 5 years) and short (≤ 5 years) term duration when it was included in the univariable and multivariable analysis. Inter- and intraobserver agreements were determined by the evaluation of intraclass correlation coefficients (ICCs). All statistical analyses were performed with SPSS version 23.0 , and two-tailed The main clinical characteristics of the T2DM patients and control subjects are shown in Table As demonstrated in Table The LV upslope and max SI significantly and gradually deteriorated from controls to patients without DPN to patients with DPN . In addition, the TTM was higher in both patient groups than in the controls , but it was not different between the patient groups (p > 0.05).The LV GLS declined significantly from controls, to patients without DPN, to patients with DPN (p < 0.001). Compared with the control group, LV GRS and GCS were decreased in both patient groups (both p < 0.05) but were not different between the groups .The results of univariable and multivariable linear regression analyses for perfusion parameters in T2DM patients are shown in Table The results of univariable and multivariable linear regression analyses for LV GLS in T2DM patients are shown in Table Table In this study, we found some important results as follows. LV myocardial perfusion and myocardial deformation were worse in T2DM patients without DPN than in the controls, and they were further deteriorated in patients with DPN. Impaired myocardial microcirculation and DPN were independently associated with subclinical LV systolic dysfunction in patients with T2DM.The pathophysiology of cardiomyopathy related to T2DM is complex and multifactorial. Among these, coronary microvascular abnormalities, are considered a comprehensive result of endothelial dysfunction, microvascular rarefaction, and perivascular collagen and AGE deposition . A previDPN can be considered a part of the continuum of disease-related microvascular complications, which include peripheral neuropathy, nephropathy, retinopathy and diabetic cardiomyopathy, and indicate a systemic rather than organ-specific disease , 7, 24. Epidemiologic studies have provided substantial evidence that there is worsened cardiac function and higher cardiovascular mortality in patients with DPN. In a diabetic rat model, there was co-occurrence of myocardial dysfunction and peripheral insensate neuropathy . We founCoronary microvascular dysfunction, as a direct cause of myocardial tissue hypoxia, is an important factor involved in the development of diabetic cardiomyopathy. Multivariable regression analyses showed negative association between DPN and LV myocardial perfusion and myocardial function. The negative association between DPN and LV GLS suggested that DPN was an important indicator of LV systolic dysfunction. We found that worsened microvascular dysfunction associated with DPN was negatively associated with LV systolic function in patients with T2DM, which was in line with previous results , 32. In There are several limitations in our study. First, the sample size in our retrospective study was relatively small, and the results should be verified by studies with larger cohorts or involving multiple centers. Second, invasive coronary angiography and coronary computed tomography angiography were not performed in all patients. However, significant CAD was deemed to be unlikely by comprehensive evaluation of the patients’ clinical history, laboratory results, electrocardiogram and echocardiography, which was supported by the CMR examinations. Third, Considering the contraindications and potential risks associated with cardiac stress test, our study solely evaluated microcirculation function at rest. However, even in the resting state, our results showed impaired myocardial microcirculation in both T2DM patients without and with DPN, and the clinical significance of resting myocardial perfusion assessment warrants further attention and validation. Finally, we could not determine the causal relationship between LV myocardial dysfunction and microvascular dysfunction due to the cross-sectional nature of the study. Further longitudinal studies are needed to explore the potential prognostic value of impaired myocardial perfusion and deformation in T2DM patients with disease complicated by DPN.In T2DM patients, there was more severe myocardial microvascular impairment and deformation dysfunction in patients with complicated DPN, and deteriorated subclinical LV systolic dysfunction was associated with myocardial microvascular dysfunction.


Hyperthyroidism is a prevalent cause of atrial fibrillation (AF). High cardiac output with low systemic vascular resistance, driven by hyperthyroidism, is associated with a rapid heartbeat, enhanced left ventricular systolic and diastolic function, and a higher incidence of supraventricular tachyarrhythmias. After returning to euthyroid status, hyperthyroidism-induced AF generally spontaneously reverts to sinus rhythm (SR), and a significant number of patients remain in chronic AF and require electrical cardioversion (ECV). After effective cardioversion, the long-term outcome of hyperthyroidism-induced persistent AF is unknown. Early ECV before the antithyroid medication should be explored for hyperthyroidism-induced AF to reduce the risk of thromboembolic consequences. The recurrence rate of AF between Hyperthyroid and Euthyroid Patients after ECV did not significantly differ. This review article compares the recurrence rate of AF as an outcome of ECV in Hyperthyroid induced atrial fibrillation. Acute atrial fibrillation (AF) is fast, irregular, and inchoate atrial activity. Increasing age, cardiovascular illness, alcohol, diabetes, and lung disease are all risk factors for acute AF. Acute AF raises the risk of cardiac failure and stroke. In more than half of the cases, the illness resolves within 24 to 48 hours; however, many others will require medical intervention to regulate heart rate or restore sinus rhythm (SR) . The worFrost et al. looked for a new-onset diagnosis of AF or Atrial flutter (AFL) in 40 628 people with new-onset hyperthyroidism who were being observed in an inpatient setting for 30 days following their hyperthyroidism diagnosis [Research employing an isolated heart model has demonstrated that experimental thyrotoxicosis animals' hearts beat rapidly and had shorter mean adequate refractory periods than euthyroid animals' hearts . The hypThe first external electrical cardioversion (ECV) procedure occurred in the 1950s. This early experience showed that electrical energy sent to the thorax from the outside could activate the heart. Zoll et al. effectively terminated ventricular fibrillation in a patient using externally administered defibrillation shocks , a batteHyperthyroidism and atrial fibrillationThyrotoxicosis is the most prevalent treatable cause of AF, with a confirmed 5-fold increased risk. In hyperthyroidism and triiodothyronine (T3) toxicosis, the elderly are more likely to have AF. Low Thyroid Stimulating Hormone (TSH) levels correlate positively with the risk of AF, and subclinical hyperthyroidism is associated with a threefold increase in AF . A low bFurthermore, the association between serum fT4 and AF remained obvious when the analysis was restricted to individuals categorized as euthyroid when blood TSH levels were normal . PatientCompared to the general population of that age without a diagnosis of AF, a considerably greater incidence of hyperthyroidism was detected throughout the 13-year follow-up, particularly in the between-the-ages-of-51 and 60 male groups . AF can PathophysiologyThe heart's β1-adrenergic and M2-muscarinic receptors are altered by high thyroid hormone in hyperthyroid patients, resulting in enhanced sympathetic activity, tachycardia, and a shorter atrial refractory time. The thyroid hormone is also known to function in ionic channel alteration. The effects of thyroid hormone on messenger ribonucleic acid (mRNA) expression and currents of key ionic channels in murine atria were investigated by Watanabe et al. . The autHyperthyroidism increases the resting heart rate, blood volume, stroke volume, myocardial contractility, and ejection fraction, which is analogous to an increase in adrenergic activity. Additionally, diastolic relaxation is improved in this condition. Furthermore, the therapeutic benefits of beta-blockers show that elevated catecholamine activity is the root cause of the cardiac symptoms of hyperthyroidism. Plasma catecholamine levels are low or unaltered in thyrotoxicosis, whereas tissue-dependent and time-dependent increases in adrenergic receptor density improve the tissue's sensitivity to catecholamines. To maintain cellular sensitivity to beta-1 adrenergic agonists, thyroid hormone decreases the expression of cardiac-specific adenylyl cyclase catalytic subunit isoforms and increases the number of beta-1 adrenergic receptors and guanosine triphosphate binding proteins .The development of AF in hyperthyroidism may be affected by several factors, including elevated left atrial pressure, which increases left ventricular mass and inhibits ventricular relaxation, elevated resting heart rate-induced ischemia, and elevated atrial ectopic activity. Premature complexes in the pulmonary veins are the origin of AF, and a re-entry pathway is required for their persistence ,14. InstEffect of persistent atrial fibrillationAF is an independent risk factor for thromboembolic events , and it Electrical cardioversionECV is usually done with continuous Electrocardiogram (ECG) monitoring and intravenous procedural anesthetic; resuscitation procedures should be considered due to the danger of ventricular fibrillation and asystole. The defibrillator/cardioverter electrodes can be positioned anterior-left lateral  or anterior-posterior such that the heart is between the two electrodes. With early monophasic defibrillators, the anterior-posterior arrangement was the most effective approach to position the electrodes . Thanks 1.7% of newly hyperthyroid people had persistent AF . The iniElectrical cardioversion in hyperthyroid-induced atrial fibrillationSince the length and severity of atrial stunning are significantly influenced by the duration and intensity of AF, restoring SR as soon as it is practically possible reverses atrial stunning and reduces the risk of thromboembolic consequences. To reduce the risk of thromboembolic consequences, early ECV before the antithyroid medication should be explored for hyperthyroidism-induced AF .Nakazawa et al.  assessedAccording to Ari et al. , 20 of 5In a study by Gurdogan et al., the average follow-up for the hyperthyroid group was 23.63 ± 3.74 months, while the average follow-up for the euthyroid group was 22.78 ± 3.15 months (p = 0.51); 14 (43.8%) and 21 (44.7%) individuals in each group relapsed with AF (p = 0.93) represented in , non-sustained ventricular tachycardia (VT), atrial arrhythmia, heart block, bradycardia, transient left bundle branch block, myocardial necrosis, myocardial dysfunction, transient hypotension, pulmonary edema, skin burn, and transient left bundle branch block. Pain at the application location is correlated with the number of applications. In stable patients with a left atrial thrombus and insufficient anesthetic, the ECV is contraindicated . Figure Thromboembolic events associated with electrical cardioversionCardioversion for AF or AFL is usually safe but is associated with a higher risk of thromboembolic incidents. The risk of thromboembolic events does not appear to differ between Pharmacological Cardioversion (PCV) and Electrocardiographic Cardioversion (ECV) or AF and AFL. Thromboembolic event after cardioversion is defined as the creation and subsequent embolization of new thrombi in the atrium that arise when the atrial function is still compromised in the weeks following cardioversion or the embolization of pre-existing thrombi in the atrium at the time of cardioversion .Temporal relationship of thromboembolic events after cardioversionData from 32 trials (published up to 1997) and 4621 patients, including 92 patients who had a thromboembolic event after ECV, were used by Berger and Schweitzer  to analyLimitationsCardioversion in persistent AF due to hyperthyroidism needs further randomized studies. Studies included in this review article had a small sample size. Furthermore, studies with longer follow-up periods are required to know the AF recurrence rates.Hyperthyroidism is the most frequent, curable, and preventable cause of AF. The development of AF in hyperthyroidism may be influenced by various causes, including elevated left atrial pressure, which increases left ventricular mass and impairs ventricular relaxation, ischemia brought on by a rapid resting heart rate, and elevated atrial ectopic activity. Atrial fibrillation is one of the Independent risk factors for thromboembolic events. Particularly in subclinical hyperthyroidism individuals without waiting for a euthyroid state, early electrical cardioversion should be considered for hyperthyroidism-induced AF. The risk of thromboembolic effects would be decreased by quickly restoring SR. Although cardioversion for AF or AFL is generally considered safe, there has been evidence linking the procedure to an increased risk of thromboembolic events. As a result, current recommendations suggest using anticoagulants for up to four weeks following cardioversion. More prospective trials with a large sample size are required to prove the advantages of early electrical cardioversion during the treatment strategy for AF caused by hyperthyroidism.


D/VT) may be a surrogate for right ventricular to pulmonary artery uncoupling (RV–PA) during cardiopulmonary exercise testing (CPET) to explain persistent exercise limitations. (2) Methods: We investigated 197 patients with heart failure and reduced ejection fraction with (n = 89) and without  LVAD. As a primary outcome NTproBNP, CPET, and echocardiographic variables were analyzed for their potential to discriminate between HFrEF and LVAD. As a secondary outcome CPET variables were evaluated for a composite of hospitalization due to worsening heart failure and overall mortality over 22 months. (3) Results: NTproBNP  and RV function  discriminated between LVAD and HFrEF. The rise of endtidal CO2  and VD/VT  were higher in LVAD patients. Group , VE/VCO2 , and ventilatory power  were best associated with rehospitalization and mortality. (4) Conclusions: LVAD patients displayed higher VD/VT compared to HFrEF. Higher VD/VT as a surrogate for RV–PA uncoupling could be another marker of persistent exercise limitations in LVAD patients.(1) Background: The exercise capacity of patients with a left ventricular assist device (LVAD) remains limited despite mechanical support. Higher dead space ventilation (V Further29 ± 8%) . Our pop2peak. Its predictive power has to be evaluated with care because the specificity was slightly above 50%. A retrospective multicenter study of 450 LVAD patients showed that a VO2peak > 12 mL/min/kg and a VE/VCO2 slope > 35 were associated with a one-year survival of 100% [2peak was higher in our study , we observed device-specific complications during the 22 months follow-up. This may illustrate that other (exercise-independent) confounders play a role in assessing mortality. Mortality in LVAD was mainly driven by device-specific complications, such as sepsis or bleeding, which may not necessarily be associated with exercise capacity. Two deaths in the HFrEF group occurred due to cancer sequelae (one with acute respiratory decompensation and one due to tumor obstruction), which may not be associated with cardiac, circulatory, or ventilatory capacities during exercise. The major factor to evaluate overall mortality in our patients was VO of 100% . Althoug2 increase) has been shown to be a determinant of rehospitalization in our study. Right ventricular dysfunction may exacerbate ventilation, but pulmonary co-morbidities may increase right ventricular afterload, which further deteriorates ventilatory efficiency. Furthermore, adequate RV–PA coupling is also facilitated by pulmonary and abdominal mechanics: the treatment of obstructive sleep apnea and obesity hypoventilation syndrome, which often co-exist with heart failure [We found TAPSE to be a major determinant of reduced exercise capacity in the groups irrespective of heart failure etiology. Lower TAPSE was associated with a higher rate of atrial fibrillation and valve dysfunction both in HFrEF and LVAD patients. Thus, guideline-directed treatment of valve dysfunction as well as adequate rate and/or rhythm control in HFrEF patients should be considered pivotal to delay the decline of exercise capacity and morbidity. Furthermore, CRT-D was associated with higher TAPSE in our HFrEF patients, which emphasizes the importance of adhering to heart failure guidelines to postpone right heart dysfunction and failure. Whether interventional treatment  plays a role in improving performance and preventing rehospitalization in LVAD patients is not known. Inefficient ventilation  Echocardiographic measurement of systolic pulmonary artery pressure to calculate TAPSE/sPAP could not be adequately achieved in LVAD patients due to limited imaging quality.There are limitations in this study: (1) We performed a retrospective data analysis, which was not powered for the primary outcome; (2) The analysis of compound variables CP and VP need to be interpreted with caution, since peak systolic pressure was not measured invasively but with a standard blood pressure cuff. Although these variables are promising, prospective studies comparing invasive and non-invasive blood pressure measurements are warranted; (3) Capillary blood gas analysis was not available to precisely detect diffusion limitations in the population. Thus, dead space ventilation was estimated from endtidal COD/VT during exercise despite increased alveolar perfusion. Thus, RV–PA uncoupling as the correlate of reduced exercise capacity in LVAD patients could be driven by impaired ventilatory mechanics as an independent factor but also as the result of reduced right ventricular function. Ventilatory mechanics and their independent prognostic value in LVAD patients need to be further investigated.Compared to HFrEF, LVAD patients displayed reduced TAPSE and higher V


The infusion of atenolol (10 nM) reduced basal LVDP and blocked the increases in LVDP induced by 6-ND (0.01 pmol), without affecting the increases in LVDP induced by 10 nmol of dopamine and noradrenaline and that induced by adrenaline (100 nmol). Conclusions: 6-nitrodopamine is the major catecholamine released from rat isolated ventricles. It is 1000 times more potent than dopamine and noradrenaline and is selectively blocked by atenolol, indicating that 6-ND is a main regulator of heart inotropism.Background: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism. Methods: Catecholamines released from RIV were quantified by LC-MS/MS and their effects on heart inotropism were evaluated by measuring left ventricular developed pressure (LVDP) in Langendorff’s preparation. Results: 6-nitrodopamine was the major released catecholamine from RIV. Incubation with L-NAME (100 µM), but not with tetrodotoxin (1 µM), caused a significant reduction in 6-nitrodopamine basal release. 6-nitrodopamine release was significantly reduced in ventricles obtained from L-NAME chronically treated animals. 6-nitrodopamine (0.01 pmol) caused significant increases in LVDP and dP/dt When th cyclase . The cur cyclase ,10. Inde cyclase  or enoxi cyclase  provokes cyclase .Chelonoidis carbonarius [Callithrix spp. [−/−, but not in nNOS−/− or iNOS−/− mice [1-adrenoceptor antagonists atenolol, betaxolol, and metoprolol, since the concentrations employed had no effect on the chronotropism increases provoked by the classical catecholamines [The novel catecholamine 6-nitrodopamine (6-ND) is released from the human umbilical cord artery and vein , aortae bonarius  and the rix spp. , and humrix spp.  and rat rix spp.  and righrix spp. . In the rix spp. . Incubatrix spp. . Indeed,−/− mice . Anotherolamines .Since noradrenaline and adrenaline are considered potent stimulators of heart inotropism , whetherThe animals  were acquired from CEMIB-UNICAMP . The protocols were approved by the local ethics committee  according to the Brazilian Guidelines (CONCEA) ; and theAnimals were given filtered water containing L-NAME at a dose of approximately 20 mg/rat/day for a minimum of 4 weeks and a maximum of 6 weeks . Control2 2.5, MgSO4 1.7, NaHCO3 24.9, KH2PO4 1.2, dextrose 11, sodium pyruvate 2, pH 7.4) continuously gassed with a mixture (95% O2: 5% CO2) at 37 °C, supplemented with ascorbic acid (1 mM) to prevent catecholamine oxidation [Isoflurane overdose was employed for euthanasia and the animals were exposed to a concentration greater than 5% until 1 min after breathing stopped. Exsanguination was performed to confirm the euthanasia. After euthanasia, the chest was opened and the heart was rapidly excised. The right and left ventricles were isolated en bloc from each rat heart and suspended in a 5 mL organ bath containing Krebs–Henseleit solution  containing ascorbic acid (1 mM) for 30 min. Two 2 mL aliquots of the supernatant were transferred to black Eppendorf tubes and stored at −20 °C until analysis [The right and left ventricles en bloc from each rat were suspended in a 5 mL organ bath containing KHS  at constant flow (10 mL/min) and maintained 4-10 mm Hg left ventricular end-diastolic pressure (LVEDP) during initial equilibration [Heparin (1000 IU/kg) was injected i.p. to prevent blood clotting and euthanasia was performed as described earlier . Exsanguibration . A watern = 5), 0.1 (n = 6), 1 (n = 6), and 10 (n = 6) pmol of 6-ND, 23 animals were employed).Following an equilibration period of at least ten minutes, a single bolus (10 mL) of 6-ND , dopamine , noradrenaline , or adrenaline  was injected. One heart was used for a single drug and for a single dose  infusion of atenolol  was performed before the bolus injection of 6-ND (1 pmol), dopamine (10 nmol), noradrenaline (1 nmol), and adrenaline (1 nmol). The heart was monitored for 15 min. One heart was used for a single drug and a single infusion.−1. The maximal rate of rise of the left ventricular pressure (+dP/dtmax) was monitored continuously by a pressure transducer connected to a PowerLab system  and expressed as mmHg × s−1. Changes in LVDP were expressed as the increase above the baseline. Data of the heart rate are presented as beats per minute (bpm). The results are presented as the mean ± standard error of the mean (SEM). Paired and unpaired t-tests were used when appropriate. Comparisons among three or more groups were evaluated using one-way ANOVA, followed by Newman–Keuls test. Actual p values are described in Figures.The left ventricular developed pressure (LVDP) was calculated as the difference between the systolic and end-diastolic pressure values, received from the LVDP curve. Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVeDP), and heart rate (HR) were continuously recorded by a PowerLab System . Left ventricular developed pressure (LVDP) was calculated by the following formula: LVSP-LVeDP and expressed in mmHg. Rate pressure product (RPP) was calculated by the following formula: HR times LVDP and expressed as beats × mmHg × minThe reagents and suppliers are described in n = 6). The basal release of 6-ND was also decreased in the ventricles obtained from rats chronically treated with L-NAME (n = 11). The incubation of rat isolated ventricles with TTX  had no effect on the 6-ND basal release (n = 6). Dopamine, noradrenaline, and adrenaline levels were undetected in all samples (limit of quantitation was 0.1 ng/mL).The isolated ventricles A–C preseh L-NAME B, n = 11 release C, n = 6.max; The animals were chronically (4-6 weeks) treated with L-NAME (20 mg/day) in the drinking water, and the hearts were isolated and perfused in vitro (Langendorff’s preparation). The hearts obtained from the chronically L-NAME-treated animals presented a significantly lower left ventricular developed pressure A, lower A bolus injection of 6-ND (0.01 pmol) caused a significant increase in the LVDP A. Furthemax  caused a significant increase in the dP/dtmax A. Furtheong them A. In conong them B, noradrong them C, and adong them D caused dopamine B, noradrdopamine C, and addopamine D caused A bolus injection of 6-ND (0.1 pmol) caused a significant increase in the heart rate A. FurtheThe infusion of atenolol (10 nM and 100 nM) almost abolished the increases in the LVDP induced by 1 pmol of 6-ND A. Atenolmax induced by 1 pmol of 6-ND  almost abolished the increases in the dP/dt of 6-ND A. The in 1 nmol; D, withou 1 nmol; B or nora 1 nmol; C. The in 1 nmol; B, noradr 1 nmol; C, and ad 1 nmol; D.The infusion of atenolol (10 nM and 100 nM) significantly attenuated the increases in the heart rate induced by 1 pmol of 6-ND A. The inmax (The infusion of atenolol (10 nM) caused significant reductions in the LVDP A, the dPmax B, the bamax C, and thmax D.2−) oxidation, formed by the degradation of NO to the nitrogen dioxide radical (NO2.), as observed with mammalian heme peroxidases [−/− mice, but is not reduced in nNOS−/− mouse [6-ND is released from the whole heart; as it is not only the main catecholamine released from rat isolated ventricles, the results presented here extend our original observation that 6-ND is the major catecholamine released from rat isolated atria . As obseoxidases  and myeloxidases . The fin/− mouse , indicatThe results with Langendorff’s preparation demonstrate that 6-ND is a very potent positive inotropic agent, being more potent than dopamine and noradrenaline (one thousand times) and adrenaline (ten thousand times). 6-ND should be considered the most potent endogenous inotropic agent ever reported. Since the synthesis/release of 6-ND from the ventricles is significantly reduced following both acute and chronic inhibition of NO synthase, the finding that rat hearts from chronically L-NAME-treated rats present decreased LVDP is compatible with the major physiological role of 6-ND as a modulator of heart inotropy; however, those hearts present extensive areas of fibrosis and myocardial necrosis , which cW-nitro-L-arginine (L-NNA) provoked relevant decreases in both left ventricular pressure and dP/dtmax [G-Methyl-L-arginine acetate salt (L-NMMA), in the rat isolated perfused heart caused an approximately 40% reduction in coronary flow and 60% in cardiac output [max to decrease from 2718 ± 170 to 2070 ± 137 mm Hg/s−1 and left ventricular peak pressure to decrease from 105 ± 9 to 86 ± 5 mm Hg [max , but had no effect on mean aortic pressure or right atrial pressure, indicating that endogenous NO has a positive inotropic effect in the normal human heart [−1) provoked important decreases in total cardiac output and stroke volume [The inhibition of NO synthase does cause coronary vasoconstriction , and cordP/dtmax . The infc output . In the  5 mm Hg . In vivoan heart . In Longe volume . Interese volume ,45,46,47+/K+-ATPase in the cell membrane [+/K+-ATPase at the sarcolemma, increasing the intracellular calcium content during systole and improving contractility [+/K+-ATPase since the use of digoxin is associated with a significant reduction in heart rate [Although the mechanism responsible for the inotropic action of 6-ND is not known, the finding that it also has positive chronotropic action may provide some clues. For instance, positive inotropic drugs increase the force of myocardial contraction through different pathways. The oldest, cardiac glycoside digoxin, works directly on myocardium and inhibits Namembrane , resultimembrane . Istaroxactility . It is uart rate , and istart rate .2+ and stabilizing the troponin C conformation [2+ remains to be investigated.Levosimendan, a pyridazinone-dinitrile derivative, is a positive inotropic drug with a different mechanism of action. It behaves as a calcium sensitizer, increasing troponin C affinity for Caormation . Levosimormation . The useormation ; while 6Other positive inotropic agents increase cardiac contractility through pathways such as an increase in cyclic AMP levels either by stimulation of adenylyl cyclase or by inhibition of type-3 PDE . The PDE1-receptor stimulation in ventricular myocytes activates the Gs-adenylyl cyclase-cAMP-protein kinase A (PKA) with consequent phosphorylation of PKA substrates including L-type calcium channel, cardiac troponin I, and cardiac myosin-binding protein C, causing an increase in calcium transients and contractility [1-adrenoceptors by catecholamines is responsible for positive inotropy [1-adrenoceptor antagonists, atenolol, betaxolol, and metoprolol, reduced the atrial frequency at concentrations that selectively blocked the increases in atrial rate induced by 6-ND, indicating that the reduction in heart rate induced by β1-adrenoceptor antagonists could be due to specific inhibition of the 6-ND receptor, rather than the β1-adrenoceptor [βactility . In paceinotropy . It is inoceptor . Indeed,Although the mechanism(s) by which 6-ND causes a positive inotropic and chronotropic effect in the rat isolated heart is unclear, the remarkable potency of this endogenous novel catecholamine presents interesting therapeutic possibilities, mainly in acute heart failure (AHF). This clinical syndrome, identified by a sudden worsening of AHF symptoms , is one 6-ND has potent positive inotropic action, presenting a potential novel therapeutic approach in acute heart failure.


IntroductionDyspnea is among the most prevalent symptoms experienced by patients presenting as an emergency. The underlying etiology is often a cardiovascular or pulmonary condition, of which heart failure is recognized as a major contributor. The differentials are primarily established based on the patient's clinical presentation and physical examinations but are not conclusive. Of the various investigations undertaken to determine the cause of dyspnea, the biomarker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) was found to be significantly associated with heart failure. Its level has been proven to be in direct correlation with the severity of the disease. This study demonstrates the usability of an economical rapid test kit in measuring NT-ProBNP levels to help differentiate the cause of dyspnea in the presenting patient in a resource-limited setting.MethodologyWe studied 115 participants from a tertiary care center in India, which included 70 males and 45 females aged ≤30 to ≥75 years, presenting with shortness of breath. Rapid NT-ProBNP tests were conducted alongside recording their symptoms, vitals, examination findings, and other parameters. They were also classified according to New York Heart Association (NYHA) Classification, and further investigated.ResultsThe study elucidated the efficacy and accuracy of the rapid kits in determining NT-ProBNP levels, and its relation with the severity and prognosis of heart failure. The kits utilized had a sensitivity of greater than 93% for ruling out heart failure as a cause of dyspnea, and a sensitivity of greater than 96% for ruling out elevated NT-ProBNP levels in general. Other parameters such as presenting symptoms and vitals were also analyzed, establishing a correlation with NT-ProBNP levels. ConclusionThis study guided us in understanding the effective utilization of the rapid testing kits for emergency care, minimizing the burden on other limited resources. The lower cost and ease of use would serve as a quick means of reaching a conclusive diagnosis, especially in an emergency, which in turn would aid in receiving timely and specific treatment. These kits could act as a stepping stone in creating a sustainable and efficient healthcare system for patients as well as healthcare workers.  Dyspnea is a common reason for emergency department admissions worldwide. Diagnosis is often difficult in patients presenting with breathlessness as there are multiple causes for the same. Usually, this condition is diagnosed clinically due to the limited availability of confirmatory diagnostic tools and, therefore, the use of biomarkers at the point of care might help in narrowing the diagnosis ,2. HeartWe commonly diagnose heart failure using the Framingham criteria, requiring two major criteria or one major and two minor criteria for reaching the final diagnosis . Major cAtrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are two peptides secreted by the heart primarily in response to stretching of the heart muscle caused by increased volume load. These peptides are initially synthesized as preprohormones and later converted into active endocrine peptides  and their N-terminal prohormone fragments, detectable in the bloodstream. The natriuretic peptide system is most prominently activated in cases of ventricular dysfunction . HoweverThough there are recent advances in the use of biomarkers such as BNP and NT-ProBNP, the use of it in tertiary hospitals is limited. NT-ProBNP assays are traditionally performed using laboratory-based whole blood immunoassay, but lately, rapid diagnostic kits have been developed that can measure serum BNP levels in the emergency department itself within 10-15 minutes. These kits have proved to be extremely affordable and equally efficient as compared to traditional assays ,9. This We analyzed 115 adult patients presenting with dyspnea in the emergency department of Gandhi Medical College, Secunderabad, India, from January 2023 to April 2023. Sample size calculation was done using the following Cochrane formula, based on which, the required sample size was estimated to be 113.where η: sample size; Z: 1.96 ; p: 8% ; q: 92%Measurement of blood NT-proBNP level was performed within the first hour of admission using an NT-proBNP rapid test kit  Figure . The NT-The primary objective of the study was to find out the effectiveness of the rapid test using parameters such as sensitivity, specificity, positive predictive value, and negative predictive value. To estimate these, the determinants required were true positive (TP) values, false positive (FP) values, true negative (TN) values, and false negative (FN) values.TP is positive results correctly indicating the cause of dyspnea due to the presence of heart failure, TN indicates negative results correctly indicating the cause of dyspnea is NOT due to heart failure but some other etiology, FP means positive results incorrectly indicate the cause of dyspnea to be due to heart failure when, in reality, the etiology is different, and FN indicate negative results that incorrectly indicate the cause of dyspnea to be due to etiologies other than heart failure when, in reality, the etiology is heart failure.An observational study was conducted in the emergency medicine center at Gandhi Hospital, Secunderabad. A total of 115 adult patients with complaints of dyspnea on presentation were included in the study over a period of four months and were tested with the rapid NT-proBNP kits to determine the effectiveness of the kits. We also investigated complaints of various symptoms among patients Figure . The majResearch participants were located in hospitals and were admitted for various diseases for treatment. The majority of participants, i.e., 47.8% (n=55), were suffering from pulmonary causes, whereas 39.1% were admitted due to heart failure.Rapid NT-ProBNP resultsThe participants were categorized into four variables  by comparing the rapid kit results with the laboratory BNP levels and echocardiology findings Table .Based on the results from Table Given the high sensitivity (>90%), a negative result on this rapid test can aid in ruling out congestive heart failure as the cause of dyspnea and shifting focus towards determining other causes. However, high FP values led to a low specificity of the test. This test cannot be used to confirm heart failure as the cause of dyspnea in case of a positive result. Further investigations shall be required to establish a conclusive diagnosis.Among the FP distribution Table , the majIf we test the sensitivity and specificity of elevated NT-proBNP levels (including heart failure and pulmonary causes) with the rapid kit, we can get a value of 96% and 56%, respectively, with an accuracy of 59.2% Tables , 5. HencAge and gender distributionThe patient sample consisted of 70 males and 45 females Figure . Of thesThe mean age of the total population was 56 years (with an SD of 16 years); the mean age of the male population was 56.3 years (with a SD of 16.8 years) and the mean age of the female population was 55.4 years (with a SD of 14.1 years). The mean difference in age between males and females is not statistically significant (p=0.76).Dyspnea characteristicsPatients can present with variable characteristics of dyspnea. There are no set features of any particular disease presentation and, hence, it becomes difficult to establish a conclusive diagnosis just on the basis of dyspnea characteristics. There were some major etiologies Figure  seen cauThe majority of patients presented with pulmonary causes followed by cardiac causes, and very few with other etiologies Table . PulmonaDistribution of dyspnea characteristics includes onset, duration, frequency, positional changes, situational changes, diurnal variations, etc. In this study, we tried to observe the duration, onset, and presence of paroxysmal nocturnal dyspnea in the patients.Onset and duration of dyspneaThe onset of dyspnea differs among individuals and can occur spontaneously or develop with time, which can be observed in our research participants, too Figure , Table 7Forty percent n=46) of participants presented with the complaint of experiencing dyspnea for almost the past week, 57% (n=65) of participants had shortness of breath for more than a week, whereas a minimal number (n=4) had the ailment for more than one month . Left heart failure also has a higher percentage (69.6%) of patients with symptoms of paroxysmal nocturnal dyspnea, while this is not observed with pulmonary etiology. The majority of the cases (96.5%) presented with acute duration of dyspnea, of which a statistically significant difference was present between those presenting within a day in comparison to those presenting after one day (p=0.0005).Association with NYHA classWe tried to describe the severity of dyspnea, including the presence of dyspnea with exertion. The higher the NYHA class, the more severe the dyspnea presentation in the patient. Heart failure patients typically presented with greater severity of dyspnea, indicated by the majority of cases presenting with class 3 and class 4 NYHA Table .Of the total TPs (40 patients with heart failure who tested positive on the rapid kit), it was observed that the BNP levels increased with increasing severity of dyspnea , and the findings were statistically significant (p<0.05) Table . This shAssociation with co-morbidities There was no statistically significant difference observed between the severity of dyspnea and the presence of co-morbidities in heart failure patients (p>0.05). The presence of co-morbidities in heart failure patients was not found to be associated with increased severity of dyspnea Table .Blood pressure was measured in the participants during their hospital visit, which was kept on record for the studyTable . The datLow blood pressure in patients might act as a contributory factor to dyspnea with decreased circulation of blood. The correlation coefficient was -0.7, indicating that low blood pressure can potentially cause the increased presence of dyspnea, but the p-value was 0.1 (>0.05), indicating that this was not statistically significant. Among other participants, 22% (n=25) experienced elevated blood pressure, and 4% (n=5) were admitted due to their hypertension crisis.The majority of patients had normal pulse rates, whereas 34% (n=39) participants had an increased pulse rate as compared to others. Their heart rate was recorded to be elevated to 100 beats per minute, which is more than the normal range of 60-100 beats per minute by the British Heart Foundation .The saturation of oxygen (SpO2) in blood was also evaluated during the hospital visit, which was kept on record for analysis. Four percent reported very low SpO2, less than 50% (n=3); 17% (n=19) reported SpO2 in the range of 51-80, and 34% (n=39) had SpO2 in the range of 81-90. The SpO2 among the majority of participants, 47% (n=54), was above 90. The normal range of SpO2 is between 94-98% in patients, according to the British Thoracic Society .Making the correct diagnosis in suspected heart failure patients is crucial but also challenging. Studies have shown that in addition to routine history, clinical examination, and routine investigations such as chest radiography and echocardiography, measurement of natriuretic peptide levels improves diagnostic accuracy in differentiating the various causes of acute dyspnea in an emergency setting . Brain NCongestive heart failure symptoms can be perceived with variable intensity in different clinical settings, and therefore, it becomes important to assess the severity of CHF using BNP levels in accordance with the NYHA class. BNP levels of >100 pg/ml are considered abnormal, and levels >5000 pg/ml are associated with poor prognosis . The rapPatients can present with an insidious onset of dyspnea or can have a sudden exacerbation of existing chronic shortness of breath. They can also have episodic attacks and changes in dyspnea with positional differences. Underlying pulmonary infection can also make it tough to clinically differentiate it from heart failure . BecauseShortness of breath can mainly be due to pulmonary pathology or cardiovascular conditions, and it is imperative to differentiate between these due to different management approaches . Acute dThe rapid test used in this study had a high sensitivity, which can potentially aid in ruling out heart failure as a cause of dyspnea if the results are negative, forgoing the time-consuming evaluation with an echocardiogram . SpecifiSpO2 is measured primarily by pulse oximeters easily accessible at healthcare facilities. Smith et al. conducted a study based on measurements in 37,593 acute medical admissions concerning air inhalation and suggested a higher SpO2 target of 96-98% as normal oxygen saturation, and indicated that SpO2 below 90 required immediate attention and medical care to avoid hypoxia-induced cell death in human body tissues . We had Early measurement of BNP levels in patients presenting with dyspnea is also shown to reduce the total expenses of patient care for both the patient as well as the hospital . More stPatients presenting with acute dyspnea can mainly be due to pulmonary or cardiac cause and the latter are more threatening due to their differences in management outcomes. One of the major causes of cardiac dyspnea is congestive heart failure, which can be determined by measuring serum BNP or NT-proBNP levels. Higher levels often indicate increased severity of the condition and a poorer prognosis. Lately, rapid diagnostic kits are being studied to determine the presence and the level of NT-proBNP levels in the emergency department for patients presenting with dyspnea potentially due to heart failure, and these can be useful for narrowing down the diagnosis of dyspnea. This study showed a high sensitivity of the rapid testing kits (>90%), which can aid in ruling out heart failure in case of negative results. This study also showed that BNP levels can be determined using these kits, which can in turn, indicate the severity of heart failure and symptoms in general. It was observed that increased severity of congestive heart failure is associated with increased BNP levels. Overall, these kits can be an effective and economical tool to narrow down the differential diagnosis of dyspnea, especially in resource-poor healthcare setups.


Liver cirrhosis is closely associated with cardiac dysfunction. The aims of this study were to evaluate left ventricular systolic function in patients with hepatitis B cirrhosis by non-invasive left ventricular pressure-strain loop (LVPSL) technique, and to explore the correlation between myocardial work indices and liver function classification.n = 32), Child-Pugh B group (n = 31), and Child-Pugh C group (n = 27). During the same period, 30 healthy volunteers were recruited as the control (CON) group. Myocardial work parameters, which included global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were derived from the LVPSL and compared among the four groups. The correlation between myocardial work parameters and Child-Pugh liver function classification was evaluated, and the independent risk factors affecting left ventricular myocardial work in patients with cirrhosis were investigated by univariable and multivariable linear regression analysis.According to the Child-Pugh classification, 90 patients with hepatitis B cirrhosis were further divided into three groups: Child-Pugh A group (P < 0.05). Correlation analysis revealed that GWI, GCW, and GWE were negatively correlated with liver function classification to various degrees , while GWW was positively correlated with liver function classification . Multivariable linear regression analysis showed that GWE was positively correlated with ALB , and negatively correlated with GLS .GWI, GCW and GWE of Child-Pugh B and C groups were lower than those of CON group, while GWW was higher than that of CON group, and the changes were more obvious in Child-Pugh C group (The changes in the left ventricular systolic function in patients with hepatitis B cirrhosis were identified using non-invasive LVPSL technology, and myocardial work parameters are significantly correlated with liver function classification. This technique may provide a new method for the evaluation of cardiac function in patients with cirrhosis. In Asian populations, chronic viral hepatitis B is the primary cause of liver cirrhosis . CirrhotLeft ventricular systolic function and myocardial oxygen consumption can be accurately assessed with the use of pressure-volume loop measured by cardiac catheterization, but this method is an invasive examination with limited use in clinical practice . The lefLVPSL technology has been widely used in the diagnosis of many cardiovascular diseases, but no studies have yet applied it to patients with cirrhosis. We hypothesized that LVPSL might provide incremental value for the assessment of left ventricular systolic function in patients with cirrhosis. The aim of this study was (1) to evaluate the left ventricular myocardial work of patients with different degrees of hepatitis B cirrhosis by using LVPSL technology; (2) to explore the correlation between myocardial work indices and liver function classification; (3) to find the clinical factors impairing the left ventricular myocardial work.2.2.1.n = 32, 56% men, age 42.9 ± 9.4 years), Child-Pugh B group , and Child-Pugh C group . Thirty healthy volunteers were allocated to the control (CON) group . The exclusion criteria were as follows: (i) coronary atherosclerotic heart disease, hypertension, congenital heart disease and other cardiovascular diseases; (ii) patients with chronic kidney disease, chronic respiratory disease, thyroid dysfunction and other diseases that may lead to secondary heart damage; (iii) patients with gastrointestinal bleeding in the last month; (iv) diabetes, hyperlipidemia and obesity; (v) poor-quality of ultrasound images. The participant selection process is illustrated in the flowchart in From July 2020 to May 2021, a total of 90 patients with hepatitis B cirrhosis were recruited in this study, including 50 males and 40 females. The diagnosis of liver cirrhosis is based on clinical symptoms, laboratory data, imaging and pathological examination . Accordi2.2.Clinical data of all subjects were collected, such as age, BMI, BSA, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). Albumin (ALB), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and brain natriuretic peptide (BNP) level in patients with cirrhosis were obtained by standard laboratory techniques.2.3.All subjects were underwent conventional echocardiography examination according to the American Society of Echocardiography guidelines , using a2.4.(1)Global work index (GWI): the total work within the area of the LVPSL curve calculated from mitral valve closure to mitral valve opening.(2)Global constructive work (GCW): work performed by shortening in systole and lengthening during the isovolumic diastole phase.(3)Global wasted work (GWW): the negative work performed by lengthening in systole and shortening during the isolvolumic diastole phase.(4)Global work efficiency (GWE): the percentage of GCW in the sum of GCW and GWW.The stored dynamic images were imported into the Echopac version 203 workstation  in original format for offline analysis. The aortic valve closure time was marked by the anterior flow spectrogram of the aortic valve to define the duration of isovolumic contraction, ejection, and isovolumic diastolic. The software can automatically identify and track the left ventricular myocardial motion trajectory and the region of interest was adjusted by correcting the endocardial border or width until a satisfactory image was obtained. Finally, after entering the mean brachial artery blood pressure value, the software automatically obtained GLS, the LVPSL curve, and myocardial work parameters, as shown in 2.5.x2-test between the groups. Correlations between myocardial work parameters and Child-Pugh liver function classification were examined by Spearman correlation coefficients. The factors with P-value <0.05 in univariable linear regression results were incorporated into the multivariable linear regression analysis models by means of stepwise selection to detect the independent predictors of abnormal myocardial function in patients with liver cirrhosis. In the multivariable linear regression model, there was no multicollinearity between variables. Intra-observer and inter-observer variability of myocardial work parameters were assessed in 15 cirrhosis patients and 15 healthy volunteers selected randomly and tested using the intraclass correlation coefficients (ICCs). All tests were two-sided, and P < 0.05 was considered statistically significant.All statistical analyses were performed using SPSS version 26.0 software . Continuous variables with normal distribution were presented as mean ± standard deviation, and those with non-normal distribution were presented as median (interquartile range). One-way analysis of variance was used for comparison among multiple groups when the variances were homogeneous, and the least significant difference t-test was used for further pairwise comparison. The rank sum test was used to compare non-normally distributed data. Categorical variables were expressed as frequencies and percentages and compared by the 3.3.1.P < 0.05). There were no significant differences in sex, age, BMI, BSA, HR, SBP, DBP, and PP among the four groups (P > 0.05).A total of 90 patients with liver cirrhosis were enrolled in this study, with an average age of 42.1 ± 9.1 years. The clinical and laboratory characteristics of the study subjects are illustrated in 3.2.P < 0.05). Compared with the CON group and the Child-Pugh A group, Child-Pugh B and C groups had higher Dpv and lower Vpv (P < 0.05). No significant differences were identified among the four groups in terms of LVDd, LVDs and LVEF (P > 0.05).The conventional ultrasound parameters of each group are summarized in 3.3.P < 0.05). Compared with the CON group, GWI, GCW and GWE in Child-Pugh B and C groups were significantly decreased, while GWW was increased (P < 0.05). Compared with Child-Pugh A and B groups, GWI, GCW and GWE in Child-Pugh C group were further decreased, while GWW was further increased (P < 0.05). . , 4.3.4.r = −0.54, P < 0.001; GCW: r = −0.57, P < 0.001; GWE: r = −0.83, P < 0.001) and GWW was positively correlated with Child-Pugh classification . GWE showed more significant correlation than other myocardial work parameters, as exhibited in Spearman correlation analysis results showed that GWI, GCW, GWE were negatively correlated with Child-Pugh classification , and negatively correlated with GLS . The detailed data are listed in HR, ALB, TBil, Dpv, IVST, LVPWT and GLS were incorporated into the multivariable linear regression analysis model of GWE by means of stepwise selection based on the univariable linear regression analysis results. The results showed that GWE was positively correlated with ALB  Compared with the CON group, there was no significant change in LVEF in the cirrhosis groups, but the myocardial work parameters had changed. GWI, GCW and GWE in Child-Pugh B and C groups were significantly lower than those in control group, while GWW was significantly higher than that in control group, and the change was more obvious in Child-Pugh C group. (2) GWI, GCW and GWE were negatively correlated with Child-Pugh classification, while GWW was positively correlated with Child-Pugh classification. (3) GWE was independently correlated with ALB and GLS respectively.Liver cirrhosis is the terminal stage of various chronic liver diseases with high mortality rate, which can damage the function of other organs to varying degrees, and it has become a serious public health problem . As one Previous studies have shown that GLS can reflect left ventricular systolic function sensitively , 17. In The results of this study showed that GWI, GCW, GWE and GWW in Child-Pugh B and C groups were significantly different from controls, but there was no significant difference in LVEF among all groups. This indicates that myocardial work parameters may reflect subclinical myocardial function damage. Impaired liver function and portal hypertension in patients with cirrhosis can lead to increase vasodilator substances in the body, which may result in peripheral vascular dilatation and reduced afterload . In addiFurthermore, this study showed that ALB and GLS were independent predictors for GWE in patients with cirrhosis. The decrease of plasma colloid osmotic pressure and insufficient effective blood volume in patients with cirrhosis can activate the sympathetic nervous system and the renin-angiotensin-aldosterone system, resulting in a compensatory state of hyperkinetic circulation with high cardiac output and low peripheral resistance . Patient5.Several limitations of the present study should be acknowledged. Firstly, this is a retrospective, single-center study with a small sample size and needs to be expanded for further study to confirm our results. Secondly, most patients with hepatitis B cirrhosis included in this study had taken drugs to control disease progression, and the effects of drugs on left ventricular function cannot be ruled out. Thirdly, we only evaluated the global myocardial function of left ventricle, and the regional myocardial work of 17 segments was not assessed. Finally, we only included patients with cirrhosis caused by hepatitis B virus, and excluded patients with alcoholic cirrhosis or other causes, which may limit the generalizability of our findings in clinical applications.6.The non-invasive LVPSL technology can quantitatively analyze the changes of left ventricular myocardial function in patients with hepatitis B cirrhosis under different disease states. The myocardial work parameters of left ventricular were significantly correlated with liver function classification. GWE was independently correlated with ALB and GLS respectively. This technique can sensitively detect abnormal cardiac function in cirrhosis patients with preserved LVEF, which has a broad prospect of clinical application.


Downgrading implantable cardioverter-defibrillators (ICD) is becoming a common clinical scenario in an aging population with increased comorbidities and more widespread use of do-not-resuscitate orders. Therefore, more patients have had ICD therapies deactivated. However, when devices require replacement, it is unnecessary to implant a larger, more expensive defibrillator to keep therapies turned off. We describe a potential solution for patients using current technology.Three patients with ICDs and DF-4 right ventricular (RV) leads were referred for generator change procedures owing to expected battery depletion. All patients had do-not-resuscitate orders in place and were at various stages of palliative care owing to noncardiac comorbidities. Demographics are displayed in Downgrading a DF-4 ICD lead requires a specific manufacturer device owing to programming requirements. An Abbott  cardiac resynchronization pacemaker (CRT-P) device with an international standard-4 (IS-4) left ventricular (LV) port is used because of the ability to program the LV channel as the ventricular sensing channel and, importantly, timing cycle calculations. We summarize the programmability of CRT-P generators in Thus, when downgrading, the DF-4 RV lead is placed in the IS-4 LV port. The IS-4 LV port is compatible with a DF-4 pin, as step-down components of the DF-4 lead are not obstructed. The mechanics are commonly misunderstood: the IS-4 pin will not fit in a DF-4 port, but a DF-4 pin will fit in an IS-4 port . SignifiThe ventricular sensing and pacing should then be programmed to LV 1–2, which corresponds to the RV tip and ring electrodes. CapConfirm™ should be disabled, as the backup pulse is delivered through the RV port. If the patient has downgraded from a CRT device, the CRT offset timing needs to be reversed .The lead configurations should be highlighted on the device using the notes function and the importance of not changing the sensing channel documented.Downgrading a DF-4 lead to IS-4 has previously been reported in a single case report by Giedrimas and colleagues,Reducing the risk from lead intervention and procedural complexity is vital in complex patients who have limited life expectancy, and financial implications are important considerations. A CRT-P device costs approximately two-thirds of an ICD.We demonstrate the successful downgrade of 3 DF-4 ICD patients using an Abbott CRT-P generator with the DF-4 RV lead placed in the LV IS-4 port to ensure sensing and pacing functions. Furthermore, we described why this device is preferable in this setting.