Introduction: Opera singers are continuously subjected to cardiopulmonary exercise. The impact on cardiac performance has not been studied. Our aim was to verify the impact of singing on heart performance, particularly by the evaluation of ECG and deformation parameters as strain, rotation and twist. Methods: A population of 17 OS (opera singers) underwent a 12-lead ECG and 2D echocardiographic evaluation. A post-processing analysis of the images to obtain the deformation parameters was included. The data expressed as mean as SD were compared to a group of 15 high-level athletes (A). Results: In both groups, the ECG parameters, 2D standard systodiastolic parameters and pulmonary pressure were normal, and in the OS group—LVDd: 47 ± 2.75 mm, LVSd: 31 ± 3.38 mm, E/A: 1.08 ± 0.23, RV: 27.63 ± 3.38 mm; in the A group—LVDd: 51 ± 1.50 mm, LVSd: 32 ± 2.50 mm, E/A: 2.37 ± 0.73, RV: 25.00 ± 3.00 mm. Indexed LV mass was significantly greater in athletes, while ejection fraction (EF) results were higher in OS. Deformation parameters did not differ among the two groups, with the exclusion of GLS expressing a major value in athletes. Rotational parameters resulted in the OS group similar to the athletes. Conclusions: OS show myocardial performance as high as the athletes. The data obtained suggest a positive impact of regular training as an opera singer. Deformation parameters highlight the fitness status in this group with a specific remodeling in RV in the presence of normal PP. Classic music singing appears to have a training effect on the heart. Further studies are necessary to confirm this hypothesis. Opera singers (OS) perform continuous physical exercises by the vocalist movements. This represents a hemodynamic commitment, especially in the muscular and cardiopulmonary district . BreathiFrom a large group of singers in a Tuscany choir, composed of 30 subjects, a subgroup of 17 opera singers  were investigasted, on the basis of regular sing-training. All the data considered for the study (Opera Singers and Athletes) were already present in our data base, as consequence of their periodical cardiological ceck-up. on the basis of regular sing-training. They were from Italy, all Caucasian, and professional singers trained daily for at least two hours for more than five years. All participants provided informal written consent to participate in the study. The study was in accordance with the Declaration of Helsinki. An informal written consent, approved from the local ethical committee, was obtained, as is regularly performed for sports medicine and lifestyle evaluation. All the subjects were studied at rest condition. A complete anamnesis, including familiar history and potential previous diseases, was obtained. A brief story of lifestyle habits, particularly the quantity of spontaneous physical activity in terms of numbers of daily/steps or about the eventual additional programmed physical activity at moderate intensity, was investigated through a simple questionnaire (IPAQ questionnaire) [2) was obtained using the Devereux formula [Following the American Heart Association guidelines,  a comple formula . Ejectio formula . In addiThe 2D images of 4-chamber views were post-processed with X-Strain software to provide an angle-independent tool for the evaluation of velocities and strain. This software allows automatic evaluation of the dynamic properties of the endocardial border and of the subendocardial tissue from 2D B-mode echocardiographic clips. Strain analysis by speckle tracking is independent of translational motion, tethering effects of the nearby regions, and it thus allows uniformity of measurements through the normal LV myocardium. The endocardial border is drawn by the operator in a 4-chamber view on a single frame from one annulus to another; the first and last points delineate the mitral plane. Other acquisitions are from 2C- and 3-chamber views. The other regional segment points were automatically set by the dedicated software. The LPSS was measured in basal and mid-apical segments of the LW and IVS from the images captured at rest. The focused apical 4-chamber view was used for the LV and a modified apical 4-chamber view for the RV. In both views, frame rates were adjusted to between 40 and 90 frames per second.During the offline analysis  a region of interest was placed around the LV from the basal septum through to the basal lateral wall, ensuring that the entire myocardium was encompassed within. This provided six myocardial segments and an average of these provided a global index of LV longitudinal ε. For the RV, the offline analysis involved placing the region of interest around the RV lateral wall only from base to apex. From the short-axis view, captured at basal and apex segments of the LV chamber, the rotation was calculated. The net difference of the basal vs. apex rotation values gave the torsion. Technically, from that window, a short-axis image of the LV apex, as circular as possible and just proximal to the level with end-systolic LV luminal obliteration, was obtained by angulation of the transducer. The short-axis views, captured at the mitral valve plane and apex level, were later processed by the speckle-tracking X-Strain software. The software asks the operator to provide the initial position of the tracking points. . An examp) of 0.05 was considered statistically significant. Normality of variables was checked by the Shapiro–Wilk test. Because of their asymmetric distribution, all data are reported as median and quartile deviation. The comparisons between LPSS values of basal and mid-apical segments for each group were performed using the Mann–Whitney U test . Two-sided probability value  and very significant (p < 0.001) differences were observed in the two populations for several of the parameters considered. All data obtained were within the normal range. As expected, the athletes showed a significantly higher dimension of the LV chamber  with a greater iLV mass (iLV mass A 108.79 ± 11.36 g/m2 vs. CMI OS 81.05 ± 12.51 g/m2), while EF was lower (p < 0.027) when compared to OS (p < 0.024) . None from either the OS or A group had a positive anamnesis for sudden death or symptomatic cardiovascular disease. Particularly, all were negative for hypertension or diabetes. During the IPAQ investigation, most OS declared having practiced less than 3 h of physical activity per week and were therefore classified as low active or moderate active IPAQ < 700 < 2519) [00 < 2519ed to OS . The rig< 0.024) . This as< 0.024) . This as< 0.024) . Regarding the RV chamber, the FW thickness was found increased in OS, despite the presence of normal morphology and dimension . This isAccording to these results, strain parameters  were also normal in the left and right ventricle chambers, with major and significantly negative values in athletes . The rotAll the ECG parameters were normal for both groups, excluding HR, which was significantly lower in athletes as consequence of a major training. No abnormal data potentially related to eventual arrhythmic acute events were found .According to the literature, music has several beneficial effects, especially on heart hemodynamics. Studies show benefits on several cardiac aspects such as BP and HR variability ,15,16, aThe correct interpretation of this aspect, without any implication on the pulmonary pressure, will need a larger investigation. The eventual ECG abnormal pattern has also been explored in parallel. The data obtained showed that the OS have a high myocardial performance level, similar to the athletes. Despite OS being substantially less active, the echocardiographic values such as deformation parameters (twist and rotation) are comparable to the athlete group. This is the first study reported in the literature that evaluates singing practice as physical exercise. The presence of significantly higher values of FW thickness in OS with a normal pulmonary pressure is particularly relevant. This aspect can be considered in agreement with the physiological effects of constant exercise in which an artificial air column is produced. The air column acts as a sounding board for producing the voice and creates a type of slight overload in the right ventricle sections. In addition, the right venous return seems to be unaffected by this situation according to the low involvement of the right atrium volume. Therefore, the data support the positive effect of the music exercise in both heart ventricles. Furthermore, pathological ECG abnormalities were not found. Currently, only one study  reports The present study provides an initial effort to integrate subjects not yet included in sports medicine evaluation. Despite this incomplete approach in sports medicine, especially of the recent transversal interest of the sports medicine to a large population of subjects at the limit of effective training, this pilot study can be applied as a stimulus to expand this point of view. Further studies will be necessary to confirm these data and to explore in more depth the different effects of music exercise. This study is mainly limited owing to the small sample investigated; therefore, it should be considered a pilot study. Another limitation in the investigation is the absence of differences by gender. Some other aspects will need to be investigated, especially those related to long-term exposure to lyrica singing in the ergometric and spirometric exercise performance.


Heart failure (HF), in conjunction with common comorbidities such as chronic kidney disease and diabetes and medical therapies such as RAASi, predisposes to hyperkalaemia which may lead to hospitalisation and death. This paper aims to review the most current evidence surrounding the risks and management of hyperkalaemia in HF, with particular focus on recent research into RAASi including novel selective mineralocorticoid receptor blockers and novel potassium binders.The most recent evidence shows that even moderate hyperkalaemia may predispose to adverse outcomes such as hospitalisation and death. Furthermore, it may prevent patients from receiving optimal medical therapy for HF by reducing prescription of RAASi therapy. Novel potassium binders such as sodium zirconium cyclosilicate (SZC) and patiromer present potential options to reduce and prevent hyperkalaemia as well as maintain optimal RAASi dosing in HF.Management of hyperkalaemia in HF has advanced in recent years. New therapies such as SZC and patiromer are contributing to the management of acute hyperkalaemia and also access to life-saving RAASi therapies by tackling and preventing hyperkalaemia in the community. This review will discuss the challenge of hyperkalaemia in heart failure, briefly covering the physiology of hyperkalaemia before focussing on clinical outcomes and management options. In particular, the most recent evidence regarding the risks of hyperkalaemia, its impact on RAASi dosing, and the impact of novel potassium binders such as patiromer and sodium zirconium cyclosilicate will be discussed.Cardiovascular diseases, including heart failure, are a leading cause of mortality across the world and contribute massively to global disability burden . Heart f+ content exists within the intracellular compartment, with just 2% found in the extracellular fluid. Normal sK+ of around 3.5–5.0 mmol/L is maintained by several mechanisms: gut absorption of ingested potassium, movement of K+ between compartments, excretion via the kidneys, and to a limited extent by gastrointestinal excretion. Following a meal, insulin stimulates cellular uptake of K+ by increasing the activity of the Na+/K+-ATPase. Similarly, catecholamines acting at β2-adrenergic receptors stimulate cellular K+ uptake via the Na+/K+-ATPase.Around 98% of the body’s K+ excretion (90%) occurs in the kidneys and is regulated by the renin–angiotensin–aldosterone (RAA) axis. K+ is freely filtered by the glomerulus and is resorbed in the proximal tubule via the paracellular pathway and in the thick ascending limb of the loop of Henle via both the paracellular route and the Na+-K+-2Cl− transporter. Hence, only a small proportion of filtered K+ reaches the site of action of the RAA axis at the distal tubule. In the early distal tubule, Na+ is resorbed via the thiazide-sensitive Na+/Cl− cotransporter (NCC). Increasing extracellular K+ concentrations in the renal interstitium downregulate NCC activity, increasing the amount of Na+ reaching the late distal tubule. Here, and in the collecting duct, Na+ is resorbed via epithelial Na+ channels (ENaC) and K+ is secreted down an electrical gradient via renal outer medullary K+ (ROMK) and big K+ (BK) channels. Under the normal action of the RAA axis, aldosterone acts at mineralocorticoid receptors in the distal tubule and collecting duct epithelial cells to upregulate ENaC, leading to increased Na+ resorption and K+ secretion. Inhibition of the RAA axis, particularly via the use of mineralocorticoid receptor antagonists (MRAs), angiotensin-converting enzyme inhibitors (ACEis), and angiotensin receptor blockers (ARBs), may hence reduce K+ excretion by acting here.The vast majority of K+ excretion centred around gut–kidney communication [+-deficient complex meal combined with a 35 mmol oral K+ load, there was a sharp rise in K+ excretion despite MR blockade with eplerenone. This rise in K+ excretion did not occur when participants were given the oral K+ load only, suggesting the presence of a gut–kidney signalling axis for K+ excretion.Interestingly, recent evidence has emerged to suggest an aldosterone-independent mechanism of Knication . Here, t+ filtered, and by reducing aldosterone production. Lower GFRs also result in less Na+ being delivered to the distal nephron, so less Na+–K+ exchange can take place. As mentioned, MRA medications block the action of aldosterone at the distal nephron, reducing Na+ resorption and hence reducing K+ secretion.In heart failure, hyperkalaemia may be caused by RAASi medication, by heart failure itself, or by comorbidities such as DM or CKD. ACEi and ARB induce hyperkalaemia via renal vasoconstriction, effectively reducing glomerular filtration rate (GFR) and hence the amount of K+ secretion as outlined above. CKD increases the risk of hyperkalaemia through reduced GFR. DM may increase risk of hyperkalaemia through damage to the kidney, resulting in a state of hyporeninaemic hypoaldosteronism which limits K+ secretion, and was associated with hazard ratios (HRs) of 1.33 for hyperkalaemia in an analysis of the Swedish HF Registry and 1.38 in a Danish study [Heart failure may also induce hyperkalaemia per se. Effective renal hypoperfusion secondary to impaired cardiac output leads to reduced GFR, hence reducing Ksh study , 4, 5. Ish study .+ 5.5–6.0 mmol/L in patients with HF carried HRs of 2.94 for all-cause and 1.88 for cardiovascular mortality compared to normokalaemic patients. sK+  > 6.0 mmol/L carried HRs of 4.89 and 3.33 for all-cause and cardiovascular mortality, respectively. Perhaps unsurprisingly, risk of cardiovascular mortality for a given sK+ was higher for individuals with HF than for individuals with CKD.Hyperkalaemia can lead to a range of negative outcomes including emergency hospitalisation, arrhythmia, and death. In a 2019 systematic review, Palaka et al. assessed outcomes stratified by degree of hyperkalaemia . The aut+  > 5.5 mmol/L as its definition of hyperkalaemia, the authors noted that 18 of 67 studies included used a threshold of 5.0 mmol/L. Indeed, sK+ of 5.0–5.5 mmol/L in HF patients carried HRs of > 2 and > 1 for all-cause and cardiovascular mortality, respectively. A subsequent study based on the EPHESUS cohort produced a risk tool for HF patients which showed that sK+ 5.1–5.5 mmol/L carried HRs of 1.3 for cardiovascular mortality and 1.0 for HF hospitalisation, while sK+  > 5.5 mmol/L carried HRs of 2.1 and 2.2, respectively [+  > 5.5 mmol/L or > 6.0 mmol/L seem to carry the highest risk, even high-normal sK+ levels could predispose to mortality and hospitalisation in HF patients, indicating the need for close monitoring and control.While the review used sK+ of 5.1–5.5 mmol/L and > 5.5 mmol/L, respectively [In acute heart failure following a first myocardial infarction, evidence suggests that a single episode of hyperkalaemia is associated with increased risk of all-cause mortality in the first 90 days, with HRs of 2.0 and 5.6 for sKectively .There is also evidence that episodes of hyperkalaemia may predict progression to CKD. A prospective 2018 study of 2443 patients demonstrated that presence of hyperkalaemia in either both or the second of two clinic visits in a 12-month period predicted progression to end-stage kidney disease (ESKD) independent of changes in patients’ eGFR . While t+ 5.5–6.0 mmol/L to be 1.32, and for sK+  > 6.0 mmol/L to be 2.19 [The European Society of Cardiology recommends RAASi treatment for all patients with heart failure with reduced ejection fraction (HFrEF) to reduce mortality, prevent hospitalisation, and improve functional status . However be 2.19 . Hence, A 2019 study of Danish population registry data aimed to quantify predictors of hyperkalaemia in patients receiving first-time RAASi prescription, CKD, or HF . The autClinical trials examining the effects of RAASi medications report the incidence of hyperkalaemia in their cohorts; these are summarised in Table +  > 5.5 mmol/L occurred in 21% and lower eGFR, higher urine albumin, beta-blocker were associated with higher risk [2 and 68 mL/min/1.73 m2, in FIDELIO-DKD and FIGARO-DKD, respectively, which may help to explain both the rates of hospitalisation and the authors’ acknowledgement of reporting them.The FIDELIO-DKD and FIGARO-DKD trials reported 40 and 21 hospitalisations in their treatment groups compared with 8 and two hospitalisations in their control groups, respectively , 31. In her risk . These tA major shift in prescribing for HF has occurred following recent trials of SGLT2 inhibitors. Evidence has shown that SGTL2 inhibitors such as dapagliflozin and empagliflozin improve outcomes in HF patients even in the absence of diabetes , 34, andLarge trials of SGLT2 inhibitors in HF have not often reported hyperkalaemia rates specifically. However, secondary analysis of the EMPEROR-Reduced trial showed reduced rates of hyperkalaemia and reduced MRA discontinuation in patients taking MRA and SGLT2i versus MRA and placebo . In addi2 or > 60 mL/min/1.73 m2.Vericiguat is a soluble guanylate cyclase stimulator which was approved in the EU and USA in 2021 for use in individuals with HFrEF who have recently required intravenous management, and is endorsed for this use by the 2021 ESC Heart Failure Guidelines . It was + or serum creatinine in the intervention versus placebo groups. Omecamtiv mecarbil is not currently licensed for HF.Omecamtiv mecarbil, a cardiac-specific myosin activator, demonstrated a modest reduction in heart failure events and cardiovascular deaths in individuals with NYHA class III/IV HF in the recent GALACTIC-HF trial . This beManagement of hyperkalaemia in individuals with HF can be divided into acute management, management after an acute episode, and chronic management. In the last few years, novel therapies such as patiromer and sodium zirconium cyclosilicate have begun to enter clinical practise for the management of acute and chronic hyperkalaemia , 50. Bef+ in the gut lumen in exchange for Ca2+, therefore reducing intestinal absorption of K+ while increasing intestinal absorption of Ca2+. It is administered as a dispersible oral powder in doses of 8.4 g up to a maximum of 25.2 g per day. It was approved for use in the management of hyperkalaemia by the US Food & Drug Administration (FDA) in 2015 and the European Medicines Agency (EMA) in 2017. It has been shown in clinical studies to be effective in reducing sK+ and enabling use of RAASi medications in non-acute settings [+ two hours after treatment compared to standard care alone, though there was no difference between treatment groups at six hours [Patiromer is a non-absorbed cation exchange polymer which acts to bind Ksettings –53. Althsettings , pilot dix hours . A recenix hours .+ in the gut lumen in exchange for Na+. It was approved for use by the FDA and EMA in 2018 and is administered orally as a dispersible powder, initially at 10 g three times per day for 72 h, then continuing at a lower maintenance dose titrated according to sK+. Large-scale evidence for the use of SZC in hyperkalaemia has emerged over the last decade, demonstrating that SZC was effective at restoring and maintaining sK+ in patients, including those with CKD and HF [+ in individuals taking RAASi therapy as in those who were not [+ and maintaining RAASi dosing in HF patients [+  ≥ 5.8 mmol/L who were randomised to SZC plus standard care had 0.35 mmol/L lower sK+ at two hours and 0.13 mmol/L lower at four hours compared to placebo plus standard care [Sodium zirconium cyclosilicate (SZC) is also a non-absorbed cation exchange polymer but binds KD and HF –60. In pwere not . In addipatients . Similarard care . While tard care .+ measurement via both point-of-care and formal laboratory methods. The UK Renal Association recommends a five-step approach to managing acute hyperkalaemia: (i) protect the heart; (ii) shift K+ into cells; (iii) remove K+ from the body; (iv) monitor K+ and glucose; and (v) prevent recurrence , in which situation a 50 mL/h 10% glucose infusion over five hours is recommended [+. The use of sodium bicarbonate in the management of hyperkalaemia in the acute setting is controversial. Some evidence suggests it is ineffective, while some studies demonstrate a potassium-lowering effect in patients presenting with combined hyperkalaemia and acidosis [Infusion of 10 units insulin in 25 g glucose solution is recommended for patients presenting with sKommended . Insulinacidosis .+ from the body is recommended via the use of SZC in the first instance, which has a faster onset of action than patiromer and lower risk of binding to co-administered medications [Removal of Kications , 65, 66.+ [+ diet and should receive multidisciplinary support from dietetics services, where available.A patient who is receiving RAASi therapy may become hyperkalaemic but not meet criteria for acute treatment or admission. In this situation, clinicians will have to decide on a management strategy to manage the patient’s hyperkalaemia while maintaining as much medical benefit from RAASi therapy as possible. Medications with a potassium-lowering effect such as loop diuretics may be used if the patient’s fluid and electrolyte status are amenable. A recent study demonstrated that the thiazide diuretic chlorthalidone was effective at reducing blood pressure in CKD patients and also acted to reduce sK+ . While t+ closely monitored, and ensuring safety in a clinical context will likely entail close monitoring also. In addition, further research must be done into patients with HF in addition to other comorbidities. The ongoing LIFT study [We are in an exciting chapter for the treatment of hyperkalaemia in HF. New therapies such as SZC and patiromer are not only contributing to the management of acute hyperkalaemia, but offer the potential to greatly improve access to life-saving RAASi therapies by tackling and preventing hyperkalaemia in the community. Data from HF trials now routinely report rates of hyperkalaemia , but exact rates of hyperkalaemia-related adverse events such as arrhythmia, hospitalisation, or death are less well-reported. From the studies that have documented these details, however, we can see that in a clinical trial context, the risk of harm from RAASi-related hyperkalaemia is low, and the benefits of medical therapy outweigh the risks. A caveat is that participants in these trials have their sKFT study , which w


Right ventricular (RV) pacing is associated with a reduction in left ventricular (LV) systolic function, thought to be mediated by pacing-induced ventricular dyssynchrony. The prevalence of heart failure after RV pacing is reported to range from 31±3%. We studied 60 subjects with high-grade atrioventricular block and Complete Heart Block (CHB) scheduled to undergo right ventricular apical pacing. 2D echocardiography was done at baseline, 1 month and 12 months. Pacing-induced cardiomyopathy was defined as a reduction in LVEF to <45%. Strain was evaluated off-line from digitally stored images using all advanced software package ; Toshiba Medical Systems). Longitudinal strain for individual myocardial segments was measured from the apical four-chamber, two-chamber and long axis views (16 segment AHA/ASE model). None had LV dysfunction at baseline based on 2D and strain echo imaging. Subsequently 18 patients were detected to develop low GLS score (less than -14.5) at 1 month. On subsequent follow up at 1 year, all 18 patients developed LV dysfunction on 2D Echocardiography. Thus Strain imaging with GLS score helped in early detection of LV dysfunction in RV apical pacing subjects. Pacing-induced cardiomyopathy had significant association with high grade AV block with pacemaker dependency. It had no significant associations with other comorbidities like diabetes, hypertension, ischemic heart disease or with the type of medication intake. However there was a statistically significant association with heart failure. Sixty subjects with high-grade atrioventricular block and Complete heart block scheduled to undergo right ventricular apical pacing were enrolled for the study.Eligible patients were aged 18 years or over, had preserved LVEF (>55%) and second-degree or third-degree atrioventricular block. All patients were required to provide written informed consent for inclusion.Exclusion criteria were pregnancy, myocardial infarction or coronary revascularization within prior 3 months, atrial fibrillation (AF), hemodynamically significant valvular heart disease (moderate in severity), Cardiomyopathy, LVEF < 55%, New York Heart Association (NYHA) functional class III or IV, significant respiratory disease, history of carcinoma within 5 years, autoimmune disorders, rheumatoid arthritis or treatment with disease modifying drugs.All clinical investigations were conducted according to the principles expressed in the Declaration of Helsinki. Written informed consent was obtained from all participants. Baseline evaluation consisted of: (i) assessment of NYHA functional class (ii) 12-lead electrocardiogram (ECG) (iii) standard transthoracic echocardiography. The protocol required that patients undergo standardized implantation of a permanent pacemaker with positioning of the ventricular lead at the RV apex.2.1Standard two-dimensional echocardiography was performed before and after pacemaker implantation  using an XARIO 200 PLATINUM ultrasound system with a 1–5 MHz broadband phased-array probe (TOSHIBA). Two dimensional LVEF were measured using Simpson's biplane method. PIVD was defined as an absolute decline in LVEF by 5% points. PICMP was defined as a reduction in LVEF to < 45%. A single experienced Operator who was blinded to the pacing interrogation results performed all echocardiographic analysis.2.2Strain was evaluated off-line from digitally stored images using all advanced software package ; ToshibaMedical Systems). Longitudinal strain for individual myocardial segments was measured from the apical four-chamber, two-chamber and long axis views (16 segment AHA/ASE model). GLS score was assessed at baseline, 1 month and 12 months. Cut off value for LV dysfunction was GLS score of -14.5.2.3For statistical analysis data were entered into a Microsoft excel spreadsheet and then analyzed by SPSS  and GraphPad Prism version 5.P-value ≤0.05 was considered for statistically significant.3All patients had almost similar baseline characteristics at the time of inclusion in the study. GLS score was assessed at baseline, 1 month and 12 months. We found that 18 patients had a drop in GLS score at 1 month. For the purpose of analysis, the patients enrolled were divided into two groups at 1 month and followed up for the next 11 months. Group A comprised of patients with decline in GLS score at 1 month . Group BOur study showed statistically significant correlation between reduced GLS score at 1 month and decline in LVEF at 12 months. This association was statistically significant in patients with higher cumulative percentage of pacing. Statistically significant correlation was also found between decline in ejection fraction and heart failure at presentation. There was no correlation between comorbidities like ischemic heart disease, hypertension and diabetes. There was no correlation between type of cardiac medicine intake.4RV apical pacing has been known to cause pacing induced LV dysfunction. It is often clinically silent and detected late. Conventional 2D Echocardiography often fails to detect subtle changes in LV function at an early stage. Yet, there is an utmost need to detect LV dysfunction early in patients with RV apical pacing because the condition can be reversed or the decline in LVEF could be arrested by medications or upgrading to biventricular or physiological pacing.We conducted our study at IPD & OPD of Cardiology at Anamoy Super specialty Hospital  for over 12 months. We designed a proforma containing various parameters and collected data accordingly. Data collection from patients was done after explaining the purpose of the study and obtaining informed consent of the legal guardian. Most of the patients coming to hospitals were of low or middle socioeconomic status. Consent form was printed in three languages like English, Bengali and Hindi.We applied strain imaging and calculated the GLS score as early as at 1 month post pacing to detect any decline in LVEF. Our study revealed that Strain imaging not only picked up early decline in LVEF but the results were consistent with decline in LVEF by 2D method at 12 months. Moreover, there was association between high grade AV block and Complete heart block with higher cumulative percentage of ventricular pacing. Heart failure at presentation was also a potential risk factor for developing decline in LVEF in the long run.NM Sharath Babu et al. Shaan Khurshid et al. Moustafa Dawood et al. Samir Rafla et al. Victoria Delgado et al. 5Our study revealed that Strain imaging based GLS score is a sensitive tool to detect RV apical pacing induced LV dysfunction. We could detect drop in GLS score as early as one month when conventional 2D Echocardiography failed to do so. Pacing induced LV dysfunction was more pronounced in pacemaker dependent patients with higher cumulative percentage of ventricular pacing. However, these findings need to be corelated in larger randomized controlled trials.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


They underwent both of these imaging studies with images taken 24–48 h apart and followed up prospectively within the same hospital course. Results: All our cases had preserved ejection fraction (EF) > 50%. Echocardiogram showed reduced mean systolic longitudinal strain  , peak systolic strain rate   and early diastolic strain rate   in ICI-treated cases. Direct comparison between the echocardiogram vs. CMR obtained within the same hospital course demonstrated strong a correlation of LS scores  and SRS scores . The Bland–Altman plots showed that 95% of the data points fitted within the ±1.96 SD of the mean difference, suggesting an agreement among these two imaging modalities. Conclusion: In this feasibility cohort study, both echocardiography- and CMR-based strain indices illustrate changes in myocardial contractility and relaxation suggestive of ICI-induced cardiomyopathy. Our data, after validation in a larger cohort, can form the basis of myocardial imaging in cancer patients treated with ICIs.Background: Immune checkpoint inhibitor (ICI)-induced cardiac side effects in cancer patients are increasingly being recognized and can be fatal. There is no standardized cardiac imaging test to examine the effects of ICIs in myocardial morphology and function. Objective: To study the utility of echocardiography and cardiac MRI in examining regional and global changes arising from ICI-induced myocarditis and cardiomyopathy in high-risk subjects suspected to have developed ICI cardiomyopathy. Methods: We studied eight consecutive patients referred for cardiac MRI (CMR) from a comprehensive cancer center for suspected ICI-induced myocarditis and compared the data with sixteen age-matched controls. Using newly developed strain analysis algorithms, we measured myocardial strain and strain rates using echocardiography and CMR. Then, we compared the mean longitudinal strain and strain rates derived from echocardiography and CMR in the same ICI-treated cohort of patients ( Advances in cancer treatment have grown to include a new subset of therapy known as immune checkpoint inhibitors (ICIs), which are at the forefront of antineoplastic therapies for several types of cancers. These include anti-cytotoxic T lymphocyte-associated antigen CTLA-4 , anti-PD-1  and anti-PD-L1 . ICI therapy inhibits the immune evasion of tumor cells, allowing for T cell-mediated antitumor immunity [While ICI therapies have shown promising results, their toxicity profile includes various autoimmune and inflammatory conditions including cardiotoxicity ,12,13,14In this study, we aim to further study the utility of CMR in comparison to echocardiography in patients suspected to have developed ICI-related adverse events. In particular, we focused on the regional and global comparisons of mean longitudinal systolic strain, peak systolic strain rate and early diastolic strain rate between these modalities.This is a multimodality analytical study in a select group of patients selected from a single, tertiary care center, Buffalo General Hospital (BGH) and Gates Vascular Institute (GVI) in Buffalo, New York. The study was approved by the University at Buffalo Institutional Review Board. An institutional database of CMR’s from January 2017 through March 2020 were reviewed to identify patients under clinical suspicion for ICI myocarditis who underwent CMR. Age-matched population-based controls were obtained from the same database. As a result, a total of 8 cases and 16 controls were gathered to analyze echocardiography and contrast-enhanced CMR, and they were followed up prospectively with images taken 24–48 h apart.Myocarditis was diagnosed by several criterion including clinical suspicion, troponin elevation with/without symptoms, ECG changes and functional and/or structural abnormalities as noticed on echocardiography and CMR . PatientThe electronic medical records were accessed to obtain patient demographics, pertinent cardiac and medical history, electrocardiogram, echocardiography and cardiac biomarkers . Patients’ clinical presentation on initial evaluation, initial and peak troponin values and any additional pertinent cardiac imaging to evaluate etiology of presenting symptoms were included. In terms of cancer specific co-variates, cancer type, ICI treatment, single vs. combination ICI and doses of ICIs were obtained. Reports of radiotherapy and chemotherapy were also recorded.n = 8) and controls (n = 16) underwent analysis of cardiomyocyte contraction using principles of finite strain theory, as described previously [ε) was calculated along the longitudinal directions. Lagrangian strain is defined as the change in length of the myocardial segment (L) from the original length (L0) at end diastole, as shown below [All cases . Eulerian strain rate, which is based on the myocardial velocity gradient (derived from velocities v1 and v2), measures the change in strain with respect to the time at peak systole  and early diastole , as described by the following formula [Similarly, cardiomyocyte contraction and relaxation were conducted utilizing Eulerian strain rates  and right ventricular (RV) borders were manually drawn at end diastole and the software outlined the remainder of the endocardial border. Any further adjustment of the initial borders was manually performed by an experienced technician/qualified imaging professional. LV strain and strain rates were calculated globally, as well as in basal, midventricular and apical regions. RV strain and strain rates for the free wall and septal regions were also measured to analyze RV contractility.®, Arlington, VA) and transmitted to an experienced imaging interpreter. Studies were uploaded and studied offline using the vendor independent TomTec software module . Two-dimensional speckle tracking echocardiography was carried out using TomTec AutoSTRAIN, Version; Image-Com5 5.5.4.467461 to calculate segmental and longitudinal strain of the visualized left ventricle segments, as described previously [Echocardiography images were downloaded in Digital Images and Communications in Medicine  was utilized to evaluate cardiac function and perform strain analysis, as described previously [Imaging of selected patients was performed with a GE 1.5-T scanner with manufacturer recommended technical parameters. Images were obtained with patients in the supine position, with an inspiratory breath-hold and ECG gating. Scout images were taken in coronal, sagittal and axial planes. CMR protocol included balanced cine steady-state free precession (SSFP) imaging for cardiac function and mass, T1-weighted fast spin echo (FSE) sequence before and after intravenous (IV) gadolinium injection and T2-weighted triple-inversion recovery images. Delayed enhanced images were taken within 10 min of obtaining contrast. Segment version 3.2 R8531 . To compare findings from both ICI-treated and control groups on systolic and diastolic strain data between groups, independent samples Student’s tatistic . CorrelaThe interrater reliability was measured as per Cohen’s kappa statistic. B.K and S.S.S analyzed echocardiography findings with a kappa value of 0.500 (95% CI −0.020 to 1.0000) suggestive of moderate agreement. U.C.S. and S.S.S. analyzed CMR had a kappa value of 1.0000 (95% CI 1.0000 to 1.0000) reported an almost perfect agreement. These values were calculated using Graph Pad Prism 9.1.2  software.n = 7, 87.5%), diabetes , hypothyroidism  and atrial fibrillation . None of the cases  were diagnosed with coronary artery disease or myocardial infarction. The baseline clinical characteristics are shown in All eight cases were included in the study. There were three females (37.5%) and five males (62.5%). The mean age was 69.1 years (Range 54–80). Comorbidities from most to least common were hypertension , non-small cell lung carcinoma , small cell lung carcinoma  and peritoneal carcinomatosis . The pattern of ICI use was as follows: pembrolizumab , nivolumab , ipilimumab , avelumab , durvalumab  and combination ipilimumab and nivolumab . From initial ICI dose and the onset of symptoms, the mean number of days was 46 days, the median number of days was 35 days and the mode was 21 days, as shown in Malignancy from most to least common were metastatic melanoma  cases had BNP values measured. The mean CK value was 960 IU/L (Range 160–2494 IU/L). Similarly, two out of eight  cases had CKMB values measured. The mean CKMB value was 87.5 ng/mL (Range 10–165 ng/mL). In addition, six out of eight  cases had myoglobin measured. The mean myoglobin level was 1220 mg/dL (Range 39–3612 mg/dL). The data for cardiac biomarkers are presented in Mean troponin at the onset was 1.79 ng/mL (range 0.24–6.18 ng/mL). Mean peak troponin value was 2.52 ng/mL (range 0.28–6.18 ng/mL). The number of cases with troponin values that had peaked by admission was six (75% of cases). The mean BNP value was 136 pg/mL (range 34–318 pg/mL). Of note, three out of eight , chest pain , lightheadedness , incidental troponin elevation  and presyncope . All cases were found to have severe myocarditis criteria by CTCAE Myocarditis Grading. Treatment was primarily steroids in 87.5% of cases, and one case (12.5%) was treated empirically for coronary artery disease. Four cases (50%) were started on steroids on day 0, one case (12.5%) on day 1, one case (12.5%) on day 3 and one case (12.5%) on day 21 of presentation. In addition, one patient received monoclonal antibody infliximab (12.5%) in addition to steroid therapy. Five cases (62.5%) are alive and three cases (37.5%) are deceased. Cause of death includes one case with atrial fibrillation and rapid ventricular rate inducing congestive heart failure (CHF) (12.5%), one case with a cerebral vascular accident (CVA) (12.5%) and one case with multiorgan failure from metastatic melanoma (12.5%). The clinical characteristics are summarized in The most common to least common symptoms or reasons for presentation were dyspnea on exertion , sinus bradycardia with first degree atrioventricular (AV) block , sinus rhythm with old RBBB , normal sinus rhythm , sinus tachycardia  and old atrial flutter . All cases had echocardiograms with preserved ejection fraction (EF). One case (12.5%) had stage I diastolic dysfunction (New right bundle branch block (RBBB) was present in one (12.5%) case. Other changes included sinus bradycardia (function .S) and early diastolic strain rate (SRE) of healthy controls and ICI-treated cases were analyzed. Representative strain curves illustrating changes in strain over time are shown in S and SRE were all significantly lower in the basal and midventricular regions in ICI-treated patients compared to the controls. While the apical region experienced a trend in LS decline (p = 0.054) in ICI-treated patients, there was no statistically significant difference in SRS or SRE in the apical region, which might be suggestive of apical sparing in ICI-treated patients.A representative echocardiogram of an ICI-treated patient is shown in n = 3) of our patients on presentation through CMR. g = 0.803 suggests the true effect might be large and the lack of significant differences could be due to small sample size and low statistical power. However, ICI-treated patients did experience statistically significant global decreases in LV SRS and SRE compared to the controls. Additionally, cardiac MRI seemed to suggest apical sparing in ICI-treated patients, which was also observed by echocardiography.The same cohort of eight ICI-treated patients who underwent echocardiogram analyses were also examined by cardiac MRI and were compared with eight CMR controls. Abnormal LGE patterns were noted on 37.5%  who underwent cardiac imaging studies using both of these modalities. Echocardiography and CMR LS scores were correlated, r = 0.83, p = 0.012, as were SRS scores, r = 0.71, p = 0.048. The correlation between echocardiography and CMR SRE did not reach statistical significance, r = 0.42, p = 0.301, due to the small sample size. The correlation analysis carried out for echocardiography- versus CMR-derived mean longitudinal strain and strain rates showed moderate correlation   C. The Blctively) D. This sClinically, cardiac biomarkers and imaging modalities, particularly echocardiography and CMR, are used in the diagnosis of ICI myocarditis , but then = 3) of our patients presented with abnormal LGE patterns on CMR, similar to the findings reported by Zhang et al. [Previously, CMR LGE patterns were compared to EMB-proven ICI myocarditis, and the results indicated that less than half (40%) of these patients had corresponding LGE findings, thus recommending caution when used. EMB was not performed on our patients; however, 37.5% , are the initial screening test for myocardial injury and ICI toxicity . ElectroThe limitations of our study include challenges associated with imaging in patients with permanent pacemakers and implantable cardiac defibrillators. Gadolinium contrast, although relatively safe, must be used in caution in patients with a GFR < 30, with risk for nephrogenic systemic fibrosis. The MRI machine environment can lead to claustrophobia and issues related to breath holding and imaging compliance . Few limIn this multimodality retrospective feasibility study, both echocardiography- and CMR-derived strain indices illustrate changes in myocardial contractility and relaxation suggestive of ICI-associated cardiomyopathy. Our data, after validation in a larger cohort, can form the basis of myocardial imaging in cancer patients treated with ICIs.


Sepsis remains a worldwide challenge for physicians with many patients admitted to ICUs with septic shock. Septic shock management involves targeted treatment to control infections, reduce end-organ damage, and reverse the injury. Sepsis-induced myocardial dysfunction or septic cardiomyopathy remains an avenue to be explored with regard to underlying pathophysiology and definite treatment guidelines. This article has compiled various studies to explain the possible mechanisms involved in the development of septic cardiomyopathy and the existing diagnostic criteria including radiological and laboratory tests to assess septic cardiomyopathy. Furthermore, the article highlights management options currently available for physicians dealing with myocardial dysfunction secondary to sepsis. Sepsis is a dysregulated host response to infection leading to end-organ damage. Sepsis is the leading cause of ICU-related deaths worldwide . With thIn adults with septic shock, ventricular dysfunction has been observed in 60% of patients in the first three days, and global heart function is affected . A hospiThe underlying pathophysiology of septic shock secondary to severe sepsis is based on myocardial contractile dysfunction, which causes acute heart failure with low or normal diastolic pressures . This heThere is no treatment for septic cardiomyopathy; however, it is a reversible condition, and research targets earlier identification of myocardial dysfunction before changes in ejection fraction. Although various pathological mechanisms have been theorized, the underlying mechanism of dysfunction remains unclear, and further investigations are warranted. This article aims to explore the various underlying pathological mechanisms involved in the development of myocardial dysfunction in sepsis. It also touches on the correlation between pathological mechanisms and clinical manifestations of septic cardiomyopathy as well as management modalities to prevent cardiac involvement and improve mortality in sepsis.DiscussionSeptic cardiomyopathy is myocardial involvement in sepsis and is defined as myocardial depression that is reversible and resolves in 7-10 days. A postmortem necropsy study carried out by Ammann et al. in 2001 revealed myocardial injury in more than half of patients with sepsis .PathophysiologyThe pathophysiology of septic cardiomyopathy is complex, and various mechanisms have been investigated to contribute to the development of myocardial dysfunction in sepsis.Escherichia coli) against a control group of six subjects who were given intravenous saline, and left ventricular ejection fraction was measured. The study concluded that endotoxin causes depression in the left ventricular ejection fraction [Bacterial endotoxin is one principal mediator of LV dysfunction. In a 1989 study carried out by Suffredini et al., nine subjects were given an intravenous bolus of endotoxin -8 were associated with less improvement of left ventricular function after six weeks, suggesting a possible role of IL-8 in reperfusion-related myocardial injuries . A retroNitric oxide also plays a significant role in myocardial dysfunction in sepsis. Nitric oxide is produced by cardiac cells and has a crucial role in cardiac performance. Endothelial nitric oxide synthase (eNOS/NOS3) is responsible for the production of NO, which in normal hemodynamics has a positive ionotropic and lusitropic effect, while it is also responsible for metabolism and contractility in myocardial cells. While nitric oxide has a positive ionotropic effect, this is only at lower concentrations. As the concentration increases, nitric oxide has a negative ionotropic effect. High levels of nitric oxide during sepsis induce myocardial dysfunction. In an animal study carried out by van de Sandt et al. in 2013, cardiac functions were assessed in septic wild-type mice with endogenous NOS versus the control group. The study concluded that NOS3 contributed to increased bioactive nitric oxide, leading to myocardial dysfunction .The imbalance of oxidative status leading to the overproduction of reactive oxygen species (ROS) is a major contributor to myocardial injury. Free radicals are molecules with additional electrons, causing them to be highly reactive and toxic. Oxygen-containing free radicals are termed reactive oxygen species. ROS plays many important roles in the life cycle of cells including the induction of cell signaling pathway, intracellular secondary messenger activation, and cell defense mechanism. However, sepsis causes increased production of these free radicals, which cannot be countered by anti-oxidative mechanisms. These ROS lead to oxidative damage to proteins, lipids, and DNA, leading to mitochondrial damage and apoptosis and promoting inflammation . OxidatiROS also leads to the inhibition of oxidative phosphorylation in mitochondria and thus depletes the cell of ATP. This state of non-utilization of oxygen is termed cytopathic hypoxia. Various other mechanisms have been identified for mitochondrial damage in sepsis, including ischemia and hypoxia. All these mechanisms lead to the increased permeability of the mitochondrial membrane, leading to an influx of ions into the mitochondrial matrix and subsequent rupture of mitochondria, releasing proapoptotic mediators into the cell, leading to the activation of apoptosis in cardiac myocytes. This results in the disruption of the contractile apparatus of the myocyte (actin/myosin) and loss of cardiac myocytes ,20.To date, many studies have been conducted, but the current data is still not sufficient to identify the exact mechanism of the development of septic cardiomyopathy. However, many underlying mechanisms have been theorized Figure , and theDiagnosisSeptic cardiomyopathy is defined by a reversible decrease in left ventricular ejection fraction. Although echocardiographic findings in septic cardiomyopathy also include isolated diastolic dysfunction and RV systolic dysfunction, this review article will focus on LV systolic dysfunction. Echocardiography is currently the investigation of choice for the diagnosis of sepsis-induced myocardial dysfunction. Echocardiography aims to assess changes in the LV cavity and changes in LV systolic dysfunction. Systolic function measured as left ventricular ejection fraction is the first parameter described in the diagnosis of septic cardiomyopathy . BedsideThe key to therapeutic success in septic shock is early recognition of hemodynamic compromise, and echocardiography is an excellent tool for both diagnoses and monitoring of patients with sepsis. In a retrospective study carried out by Lan et al. in 2019, 3,291 patients who were admitted with sepsis from 2001 to 2012 at Beth Israel Deaconess Medical Center were studied. The study concluded that the utilization of echocardiography in patients with septic shock led to improved 28-day outcomes . SimilarThe measurement of the global longitudinal strain (GLS) via speckled echocardiography has recently emerged and is now considered more accurate in the diagnosis of myocardial dysfunction. Speckle tracking uses an automated computer algorithm that tracks movements in regions selected by the user throughout the cardiac cycle. The program allows the assessment of changes in contractility and thus LV function. Strain imaging detects changes in LV systolic function before changes in left ventricular ejection fraction, thus allowing earlier detection of myocardial dysfunction . In a 20Cardiac biomarkers are also used as a tool for the diagnosis of cardiac involvement in sepsis. Troponin I is a highly sensitive marker for myocardial damage, but it can be elevated without evidence of myocardial ischemia. In a prospective cohort study carried out by Lim et al. in 2005, 115 patients admitted to the ICU were enrolled and were categorized into those who had elevated troponin and myocardial infarction (MI) versus those who did not have MI. The study concluded that 47% of critically ill patients had elevated troponin, but only 26% had MI . ElevateB-type natriuretic peptide (BNP) is a hormone produced by the heart in response to changes in pressure inside the heart. NT-proBNP is an inactive prohormone of BNP. The levels of BNP and NT-proBNP are elevated in heart failure and have been used in the prognosis of congestive heart failure and ischemic heart disease. In a 2007 observational cohort study by Varpula et al., the predictive value of NT-proBNP in critically ill patients was evaluated. The study results showed that NT-proBNP values were increased in patients with sepsis and septic shock . In a 20ManagementThe standard treatment for sepsis focuses on infection control and hemodynamic optimization with fluid resuscitation and vasopressors. The treatment of sepsis-induced myocardial dysfunction is the same strategy. Since the dysfunction is reversible, therapies to effectively manage sepsis will lead to the resolution of cardiomyopathy . The keyThe beta-blockade has been suggested to reduce heart rate and decrease mortality in sepsis. In a randomized control trial by Morelli et al. in 2013, 77 patients with septic shock were given intravenous esmolol to reduce heart rate below 95 bpm. The study showed improved heart rates without any adverse clinical outcomes; however, mortality reduction still needed further investigation .Levosimendan is a positive ionotropic drug and increases the effect of calcium on myofilaments. Despite being ionotropic, it does not cause increased heart rate and therefore is predicted to have better outcomes in patients as compared to dobutamine. In a 2015 meta-analysis by Zangrillo et al., randomized trials of levosimendan use in septic shock were included with mortality being the primary outcome. The study concluded that levosimendan was associated with improved mortality in patients with septic shock as compared to standard ionotropic therapy . HoweverIn the case of nonresponsiveness to vasopressin and fluid resuscitation, an intra-aortic balloon pump (IABP) can be used to increase cardiac output. It can also be used to reduce the dose of vasopressors. Intra-aortic balloon pump is a mechanical circulatory support device. The IABP assists the heart by reducing afterload, leading to increased organ perfusion and coronary blood flow. An animal trial carried out by Solomon et al. in 2009 to study the effect of intra-aortic balloon counter pulsations in mechanically ventilated canine models concluded that IABC prolongs survival and reduces the need for vasopressors . While ITherefore, the management options for septic cardiomyopathy remain limited and focus primarily on treating the underlying shock augmented with fluid and vasopressor therapy to maintain cardiac output and hemodynamics. Figure This review article covers the basic pathological mechanisms suggested to lead to cardiomyopathy in sepsis and the diagnostic and prognostic markers. It also touches on the management options for septic cardiomyopathy, but as data for this is insufficient, the article is limited to the management of sepsis at large. Septic cardiomyopathy also encompasses isolated LV diastolic dysfunction and RV systolic dysfunction, which is still a debate, and thus, this article is limited to the effect of sepsis on left ventricular systolic dysfunction. There is a need for further investigation to determine the definite cause of myocardial dysfunction and novel treatment guidelines.Septic cardiomyopathy is a reversible decrease in myocardial contractility secondary to the release of bacterial endotoxin, increased inflammatory markers, increased reactive oxygen species, nitric oxide, and mitochondrial dysregulation. Septic cardiomyopathy is characterized by the dilation of the LV cavity, decreased left ventricular ejection fraction, and return to baseline LV function within 7-10 days. Septic cardiomyopathy is diagnosed by clinical signs of sepsis including low cardiac output and the development of septic shock. The investigation of choice is echocardiography to assess for changes in LV systolic function and guide management. Speckle echocardiography for the measurement of the global longitudinal strain is a novel investigation for the early detection of myocardial involvement in sepsis. Cardiac markers including high sensitivity troponin and BNP can be used to diagnose and assess prognosis in patients with nonischemic myocardial damage secondary to sepsis.The management of septic cardiomyopathy targets the management of underlying sepsis and achieving hemodynamic stability using fluid and vasopressors. The challenge is the lack of definite guidelines targeting the treatment of septic cardiomyopathy. Although a large number of studies are present on septic cardiomyopathy, there is still room for further investigation to determine the definite pathology of myocardial dysfunction and definite guidelines directed toward treating septic cardiomyopathy to improve outcomes in patients with sepsis and reduce mortality.


Persistent postural-perceptual dizziness (PPPD) is a common cause of chronic dizziness associated with significant morbidity, and perhaps constitutes the commonest cause of chronic dizziness across outpatient neurology settings. Patients present with altered perception of balance control, resulting in measurable changes in balance function, such as stiffening of postural muscles and increased body sway. Observed risk factors include pre-morbid anxiety and neuroticism and increased visual dependence. Following a balance-perturbing insult (such as vestibular dysfunction), patients with PPPD adopt adaptive strategies that become chronically maladaptive and impair longer-term postural behaviour. In this article, we explore the relationship between behavioural postural changes, perceptual abnormalities, and imaging correlates of such dysfunction. We argue that understanding the pathophysiological mechanisms of PPPD necessitates an integrated methodological approach that is able to concurrently measure behaviour, perception, and cortical and subcortical brain function. Persistent postural-perceptual dizziness (PPPD) is one of the most common causes of chronic dizziness, affecting 4% of individuals registered with general practitioners in the United Kingdom . HoweverIn 2017, a consensus committee of the Bárány society proposed diagnostic criteria for PPPD that included a sensation of unsteadiness and non-spinning vertigo, exacerbated by upright posture, active or passive motion, and exposure to moving visual stimuli or complex visual patterns . It is aHowever, the clinical phenotype can be diverse. Preceding trait anxiety and psychological stress are significant risk factors for the development of PPPD ,6, with Theoretical considerations to explain the pathophysiology of PPPD are emerging based on our understanding of the precursors to PPPD, namely chronic subjective dizziness, phobic postural vertigo, and visual vertigo ,11,12. OUnderstanding the underlying pathophysiology of PPPD symptoms has more recently focused on imaging modalities. Here, we review the clinical features and brain imaging findings in PPPD and discuss the importance of behavioural and perceptual experimental data in better understanding the pathophysiology of this disorder. Patients with PPPD present with two key fluctuating or continuous symptoms: (a) a dizzy, not-truly-vertiginous sensation, with patients reporting that their head is swimming, and/or (b) unsteadiness, such that patients report swaying, rocking, or “jelly legs” . SymptomTypically, PPPD is triggered by an acute disruption to normal balance function, whether triggered by a vestibular or non-vestibular stimulus. In the former, the development of PPPD is not, however, attributable to the degree of inner ear  dysfunction or failed ear recovery . Rather,n = 1), were review articles (n = 13), not related to the pathophysiology of PPPD (n = 9) and did not include neuroimaging (n = 7) , published between 1 January 2015 and 30 September 2020. The information sources used in this review were Medline/Ovid, Embase/Ovid and PubMed. The search strings included the following key terms “Vestibular Diseases” OR “Dizziness” OR “persistent postural perceptual dizziness”; OR “persistent perceptual postural dizziness”; OR  AND pathophysiology OR physiopathology OR pathophysiological mechanism; OR pathogenesis OR pathological OR “psychophysics”. The search criteria returned 3376 articles, reduced to 2443 after the removal of duplicates. After screening the title and abstract, a further 2405 were excluded as irrelevant. The remaining 38 full-text articles were assessed for eligibility and 30 were excluded because: they exclusively related to PPPD ( (n = 7) . The remThere can be little doubt that PPPD is a neuropsychological disorder and on this basis, there has been an assumption that patients may manifest alterations in brain function, or even structure. Are, however, the brains of patients with PPPD—or, for that matter, anxiety or neuroticism—truly different from those without, or are any neural changes perhaps transient in such individuals, mirroring their neuropsychological states? Imaging data in PPPD appear to show both functional and structural changes compared to healthy controls, but there are some important confounding factors. Below is a summary of the key imaging findings described in patients with PPPD to-date.Riccelli et al.  found inNa et al.  found reStructural brain changes have also been observed in patients with PPPD compared to healthy controls. Wurthmann et al.  found reWhilst imaging undoubtedly provides a relevant modality to explore neurological disease, current neuroimaging studies fall short of the optimal experimental design to understand the pathophysiology of PPPD . Some piWhilst it is tempting to focus on brain structure and function, imaging studies provide a static view of structure, connectivity, and activity that allow only a correlation with symptoms but cannot inform a causal link. The clinical features of PPPD highlight its essence as a primary perceptual disorder. That a functional disorder arises because of structural brain changes, and alteration in gyrification  is, in our view, difficult to account for in the context of current models of PPPD. However, perceptual dysfunction does of course lead to behavioural changes in posture and gait that may in turn effect alterations in cortical function and structure, the latter being a consequence, not a cause, of the perceptual disorder.Behavioural data, therefore, seem crucial to propel our understanding of PPPD; understand the clinical symptoms, maladaptive strategies; and eventually facilitate the design and implementation of targeted effective therapies, most likely still involving physical therapy as a core domain. The current treatment options for PPPD include: vestibular rehabilitation (VR) and physiotherapy (PT); Cognitive Behavioural Therapy (CBT); medication; and electrical stimulation. VR, PT and CBT are the most common, either in isolation or combined; however, it is recommended that CBT is always implemented in addition to any physical therapy and vice versa , a frameReports of postural control in patients diagnosed with chronic subjective dizziness  showed pParticular postural metrics have been identified in patients with functional balance disorders, such as a stiffened ankle strategy with a high frequency (3.5–8 Hz) of body sway in patients with phobic postural vertigo —a previoWe have previously highlighted the possible role of abnormal magnitude estimation in the generation of functional balance disorders , linked Indeed, at height, normal individuals overestimate magnitudes of forward leaning by up to 10% and increased soleus responses to Achilles’ tendon taps by almost 20% relative to being at ground level ,59, suggThese findings suggest that patients with PPPD rely on threat-related postural control strategies that deviate from contextually optimal control, such as a stiffened ankle-strategy, a lower threshold for engaging control loops that incorporate visually dependent feedback, increased sensitivity to motion, and increased gain of posture-related motor reflexes ,61. NeurAccordingly, to study brain images in isolation and not to correlate the data with clinical features of PPPD may not lead us to decipher the pathophysiology of PPPD—a perceptual disorder with behavioural consequences. The core symptoms of PPPD seem to arise from multi-level changes in brain function, perception, and behaviour, with a diminished sense of agency about the control of postural control. We have previously proposed that the pathophysiological mechanisms underlying PPPD involve changes in processing of multi-modal stimuli related to our immediate environment and our movement within this. Such information requires ascending brainstem pathways to be appropriately processed at a cortical level. Any alteration in conscious awareness of  motion can induce a reduced tolerance to perceived postural instability, generating a perception of heightened instability, and thus resulting in adjustments to locomotor control strategies . Furtherexclusively postural. Previously, Furman and colleagues [Considering the postural nature of patients’ complaints, understanding the pathophysiology of PPPD is likely to require dynamic behavioural data, perhaps not lleagues  have sholleagues  used an lleagues . Such stTask-based functional imaging may help uncover the basis for visual hypersensitivity, which frequently accompanies PPPD, but is less likely to inform the mechanism of perceived postural instability, the core feature of this disorder. Ultimately, PPPD research will benefit from a combination of methodologies that include postural assessments, perceptual psychophysical measures, psychological measures, and how these interact with cortical and subcortical dysfunction across brain areas (imaging) and networks mediating such functions. The latter could be achieved through a range of non-invasive techniques such as electroencephalography , magnetoThere has been some great progress in our understanding of PPPD, and a desire to improve treatments for one of the most common dizziness presentations in Neurology. Clinical studies would be strengthened, however, by experimental work exploring whether transient disruption of critical brain networks—using non-invasive brain stimulation, for example—could reproduce similar symptoms to those seen in PPPD in otherwise healthy controls. Moreover, understanding the role of altered magnitude estimates may help explain the development and perpetuation of symptoms, and the role of reduced vestibulo-cortical dominance in the generation of distorted representations of the magnitude-space-time continuum. Work is ongoing to understand the predictors of PPPD in order to intervene at the earliest possible stage and avoid development of chronic dizziness symptoms. In patients with established PPPD, however, the development of biomarkers to track progress and measure response to therapies needs to incorporate abnormal perception, not just posturography deficits or imaging abnormalities, given the degree of heterogeneity in behavioural adaptations to a perceived postural threat.


Background: Right ventricular (RV) dysfunction is a potent predictor of mortality and morbidity following acute myocardial infarction (AMI). Despite the fact that elective percutaneous coronary intervention (PCI) has significantly decreased myocardial damage to the left ventricle, there is a lack of information regarding the effect of PCI on RV function.Aim: This study aimed to examine the effect of right coronary artery (RCA) revascularization on the systolic and diastolic functions of the right ventricle following acute inferior wall myocardial infarction.Methods: Fifty-nine patients diagnosed with acute inferior wall myocardial infarction after RCA revascularization were prospectively investigated between April 2018 and January 2020. The patients underwent 2D echocardiography. RV systolic and diastolic functions were reported before and after the PCI procedure and compared using echocardiographic RV systolic and diastolic parameters.Results: After PCI, echocardiographic RV systolic and diastolic functions significantly improved in the proximal and mid RCA in terms of TAPSE, RVFAC, and E/A. Significant improvement was found in the mid RCA in terms of S′ velocity (p = 0.008) and in the proximal RCA in terms of E/e′ (p = 0.021). Overall echocardiographic systolic and diastolic parameters in patients with RV dysfunction following PCI were improved .Conclusion: Our findings revealed that patients with RV dysfunction showed remarkable improvement after RCA revascularization. Hence, in future cases, RCA revascularization may become an appropriate treatment alternative for the recovery of patients with RV dysfunction. Right ventricular (RV) dysfunction after AMI has emerged as a potent predictor for increased events of mortality and morbidity2,3. RV dysfunction has been reported in 50% of patients with inferior wall myocardial infarction and 10% of patients with anterior wall myocardial infarction4,5. Severe RV dysfunction is associated with right coronary artery (RCA) occlusion proximal to major RV branches6,7. Notably, RV dysfunction affects left ventricular function by limiting left ventricle preload. It also causes adverse effects on systolic and diastolic interactions through the intraventricular septum and pericardium (ventricular coupling)8. Therefore, the diagnosis of RV dysfunction is of utmost importance.Acute myocardial infarction (AMI) is a major cause of coronary heart disease despite breakthrough advancements in percutaneous coronary intervention (PCI) over the last few years9,10. To this end, this study aimed to examine the effect of RCA revascularization on systolic and diastolic functions of the right ventricle following acute inferior wall MI. It also analyzed the RV function response in each RCA segment following PCI.Although several studies have assessed the role of left ventricular function in the prognosis of patients with AMI, little attention has been paid to the role of systolic and diastolic RV functions. This can be due to diagnostic limitations of the electrocardiogram (ECG) and echocardiography of the irregularly shaped right ventricleThis single-center, prospective interventional study comprised 59 adult patients (age >18 years) who were referred to a tertiary healthcare center between April 2018 and January 2020. Patients who were diagnosed with acute inferior wall myocardial infarction with an angiographic diagnosis of isolated RCA lesions following PCI were included, irrespective of the thrombolysis status.The exclusion criteria in the study were: 1.stable ischemic heart disease, 2.angiographic evidence of significant lesion in arterial territory other than RCA, 3.history of chronic obstructive pulmonary disease or any other chronic respiratory conditions, 4.history of coronary artery bypass grafting or valvular surgery or previous PCI, 5.history of renal or hepatic failure, or 6.history of cardiomyopathy.Demographic data, lesion characteristics, and echocardiographic parameters were also recorded. The endpoint of the study was the improvement in RV dysfunction following PCI. Written informed consent was obtained from all the patients.11.Prior to PCI, patients were evaluated by 2D echocardiography using the Esoate MyLab™X7 machine system. Primary PCI was performed using an ultrathin (60 µm) Supralimus Grace sirolimus-eluting stent  within 24 h of 2D echocardiography. After PCI, 2D echocardiography was performed with the Esoate MyLab™X7 machine system within 24-48 h. Left ventricular function was assessed as the percent change in ventricular cavity area from end-diastole to end-systole, and the left ventricular ejection fraction (LVEF) was evaluatedThe following parameters were measured to assess RV function in the RV-focused apical four-chamber view: 1.tricuspid annular plan systolic excursion (TAPSE) was measured using M-mode echocardiography with the cursor optimally aligned along the direction of the lateral tricuspid annulus, 2.right ventricular fractional area change (RVFAC) was calculated using the following formula: (end-diastolic area × end-systolic area)/end diastolic area, 3.pulsed Doppler S wave (cm/s) and color tissue Doppler S wave (cm/s) measured peak systolic velocity (S′ velocity) of tricuspid annulus, 4.Doppler velocities of tricuspid E (early RV filling velocity) and A (late RV filling velocity) were evaluated, 5.tissue Doppler imaging study measured e’(early diastolic tricuspid annulus velocity) and a’(late diastolic tricuspid annulus velocity), thus evaluating the E/e′ ratio.The reference limits of all echocardiographic parameters were adopted from the recommendations established by the joint venture of the American Society of Echocardiography and European Association of Cardiovascular Imaging. According to these guidelines, the abnormality threshold criteria for RV systolic dysfunction parameters were TAPSE < 17 mm, RVFAC < 35%, and S′ velocity < 10 cm/s. On the other hand, the abnormality threshold criteria for RV diastolic dysfunction parameters were E/A < 0.8 and E/e′ ≥ 4.0.11.p value < 0.05. Statistical analyses were performed using SPSS statistical software version 15 .Quantitative data are presented as mean ± SD, and qualitative data are presented as frequencies. For categorical variables, comparisons between pre- and post-PCI were performed using McNemar’s test. Statistical significance was set at Of the 59 patients, 41 (69.5%) were male and 18 (30.5%) were female. The mean age of the study population was 54 ± 8.2 years. No serious periprocedural complications were noted in any patient after successful PCI. p = 0.031) and mid RCA (p = 0.004) following PCI. There was a significant difference in RV function after PCI in the mid RCA (p = 0.008) based on the S′ velocity. As per RVFAC, the improvement in RV function was found to be significant in the proximal (p = 0.004) and mid RCA (p = 0.016) following PCI.p = 0.039) and mid RCA (p = 0.016) following PCI, whereas RV function was significant only in the proximal RCA (p = 0.021) based on the E/e′ ratio after PCI.Echocardiographic diastolic parameters of the right ventricle before and after PCI are shown in . RV function was improved in 81.82% of patients with TAPSE < 17 mm, in 68.18% of patients with S′ velocity ≤10 cm/s, and in 90.00% of patients with RVFAC < 35%. There was an overall improvement in RV function in echocardiographic diastolic parameters in 75.00% patients for E/A < 0.8 following PCI, whereas 14.29% patients showed unremarkable improvement for E/e′ ≥ 0.4, as demonstrated in 12. Furthermore, our study showed rapid recovery of RV function in AMI patients after PCI, which was also reported by Popescu et al. 13. This shows the importance of revascularization of the affected RCA.In the present study, systolic and diastolic echocardiographic parameters of RV function following RCA revascularization significantly improved. However, this improvement was observed in the proximal and mid parts of the RCA in TAPSE, RVFAC, and E/A. Significant improvement was found in the proximal part of the RCA for E/e′ and the mid part of the RCA for S′ velocity. Nonetheless, no improvement was observed in the distal part of the RCA for all parameters. Likewise, Nikdoust et al. reported a significant improvement in proximal RCA revascularization14. Being a part of the right ventricle, the interventricular septum is influenced more by the left ventricle than the right ventricle, irrespective of advanced RV dysfunction or severe pulmonary hypertension. Moreover, involvement of the interventricular septum in evaluation of global RV function represents a great challenge15. Approximately 66% of the right ventricle is perfused with blood by the RCA in 85% of the world’s population through the posterolateral, atrioventricular nodal, and posterior descending arteries. The inferior wall of the right ventricle is easily affected by ischemia, whereas the infundibulum and anterior wall are unaffected segments14.The right ventricle is different from the left ventricle with respect to various anatomic and physiologic characteristics, yet they are related to each other. The shape, size, and conformity of one ventricle influences the hemodynamic features of the other ventricle, which is known as ‘ventricular coupling’Owing to the fact that the severity of RV dysfunction is based upon the region of RCA occlusion, data pertaining to the lesion sites, collateral vessels, and dominance/ codominance is of paramount importance.16.In a previous study, Hsu SY et al. al.. also stated that the region of coronary artery involvement might have a significant impact on RV function. Patients who were suffering from inferior infarction and without concomitant RV infarction, major echocardiographic parameters of RV function were identical in healthy individuals except for RV diastolic function. On the other hand, the variation in global RV function has been more prominent in patients with anterior wall infarction17–19. Conversely, the present study did not investigate any correlations between echocardiographic parameters of RV function and LVEF. Furthermore, the recovery of RV function was significant following revascularization for all echocardiographic parameters. These parameters are independent predictors of RV function.Many previous studies have shown a significant association between echocardiographic parameters of RV function and LVEFThe present study has several limitations that need to be acknowledged. First, it was a single-center study with a small sample size; therefore, this study’s outcome may not be extrapolated to the general population. Second, patients with a single vessel (that is RCA) coronary artery disease were included in this study. Presumably, patients with multivessel coronary artery disease may adversely affect the RV function. Lastly, no investigation has been conducted on the size and length of the stents used during RCA revascularization.The findings of this study showed significant improvement in systolic and diastolic RV function after RCA revascularization in the proximal and mid RCA. Further studies with larger sample sizes and multivessel coronary artery disease are needed. In addition, the stent profile and anatomical features of the stenotic artery should be considered.


He was diagnosed with suspected tonsillitis and was treated with co-amoxiclav. He was exercising over 10 hours weekly for the last two months in the gym for the Ironman triathlon in London. An echocardiogram showed severe left ventricular systolic dysfunction (LVSD) with a left ventricular ejection fraction (LVEF) of 25%. An electrocardiogram showed sinus tachycardia with a right bundle branch block (RBBB). Cardiac magnetic resonance imaging (CMR) showed normal biventricular function with an ejection fraction (EF) of 71% four months later. The patient was diagnosed with tachycardia-induced cardiomyopathy. This case is unique as the patient presented with transient severe LVSD after training for the ironman triathlon and spontaneous recovery.Tachycardia-induced cardiomyopathy (TIC) can result in both systolic and/or diastolic ventricular dysfunction as a result of the prolonged fast heart rate which is reversible upon controlling the fast heart rate or arrhythmia. The exact heart rate that can lead to this is not clear, however, a heart rate > 100 in general needs attention. Tachycardia-induced cardiomyopathy is a well-established cause of left ventricular dysfunction which usually happens due to an increased atrial or ventricular rate. The incidence of TIC is very low although the exact incidence is unclear. It should be considered in all patients with dilated cardiomyopathy or those with no obvious explanation for dilated cardiomyopathy and in presence of tachycardia or atrial fibrillation with a rapid ventricular response. Tachycardia-induced cardiomyopathy has also been labeled as arrhythmia-induced cardiomyopathy lately. We present a case of a 50-year-old patient who presented with a fever of 39 Over 800 marathon races are organized worldwide every year and several thousand individuals participate in them every year . TachycaThe relationship between tachyarrhythmia and reversible heart failure was first described by Phillips et al. in 1949 . TachycaIt is a well-known fact that chronic tachycardia can result in structural heart changes including left ventricular dilatation and cellular morphological changes . These cA 50-year-old male presented with fever, sore throat, and vomiting several times followed by collapse at home after two days of intense exercise. Past medical history (PMH) was significant with hypertension, and dyslipidemia. Regular medications include felodipine and atorvastatin. He was preparing for the London ironman triathlon and was exercising over 10 hours every week for the last two months which included heavy lifting at the gym and cardio exercises. He started to feel unwell two days prior to hospital admission. He was commenced on oral amoxicillin by his general practitioner for possible tonsillitis. Vitals on arrival were as follows: temperature of 37.1 °C, heart rate (HR) 74 respiratory rate (RR) 20, blood pressure (BP) 99/63, a saturation of peripheral oxygen (SpO2) at 96%, and weight at 68 kg. Clinical examination was unremarkable apart from mild tonsillar erythema. His chest was clear, heart sounds were normal, and he did not have any pedal edema. The electrocardiogram (ECG) showed sinus tachycardia (HR > 110) with a right bundle branch block (RBBB). Laboratory results showed only elevated serum urea 8.9 mmol/L , total cholesterol 7.0 mmol/L (0-5), troponin were 12 and 13 . Computerized pulmonary angiography showed right ventricular enlargement with right ventricle (RV):left ventricle (LV) ratio 1:1 but no pulmonary embolism . The septum was dyskinetic and RV was severely dilated Videos -3.The patient was not commenced on any rate-limiting medications due to hypotension and a repeat echocardiogram showed significant improvement in LVEF up to 45% within 48 hours without any obvious treatment Videos .The patient remained in normal sinus rhythm and did not have any further tachycardia. He was discharged home only on his regulation medications and an outpatient follow-up was arranged. He was advised to avoid intense exercises given his TIC. The patient was seen at the outpatient heart failure and arrhythmia clinic three months after discharge. Cardiac magnetic resonance (CMR) imaging showed normal LVSF, ejection fraction (EF) was 71% with no evidence of regional wall motion abnormality (RWMA) or mucosal edema, and moderate right atrial enlargement. The patient was advised against intense exercises such as marathons and to continue with his regular medications.The possible differential diagnosis, in this case, includes myocardial infarction, myocarditis, hypertrophic cardiomyopathy, and myocardial bridging. There was no evidence of myocardial infarction (MI) in this patient and the ECG did not show any features of MI. The CMR did not show any evidence of myocarditis or hypertrophic cardiomyopathy and/or myocardial bridging. In addition, his LVEF improved within 48 hours without any treatment which is highly suggestive of TIC.Tachycardia-induced cardiomyopathy is reversible cardiomyopathy with left ventricular systolic dysfunction that can be induced by any tachyarrhythmia and early recognition, and treatment mostly results in left ventricular function recovery . TachycaThe first case of TIC was discussed in 1913 in a young patient who presented with congestive heart failure and atrial fibrillation with rapid ventricular response (AFRVR) ,20. PrevSudden cardiac death (SCD) has been reported in marathon runners and the overall incidence varies from 1:50,000 to 1:220,000 . The incAnother study showed increased pulmonary artery pressure (PAPs), increased RV dimensions, and decreased RV function, and alterations in LV diastolic function. These changes correlate with troponin release and an increase in N-terminal (NT)-pro brain natriuretic peptide (BNP). These changes were found to be influenced by the participants' level of preparation for the marathon race and the most striking abnormalities were found in participants who trained ≤35 miles/week before the marathon -25. ThisClinical studies have reported improvement in LVSF within a month following the treatment of tachyarrhythmia, however, complete recovery can take two to three months and rarely takes more than six months. Furthermore, this duration can be shortened by adequate heart rate reduction treatment. Another study reported significantly higher LV volumes in patients with TIC when compared to age, sex, and ejection fraction matched controls and the key to treating TIC is to eliminate or control the culprit tachyarrhythmia which can be achieved either through antiarrhythmic medications or radiofrequency catheter ablation (RFCA) ,25. Our The LVSF returns to normal within two weeks after the rapid pacing stops and hemodynamic parameters return to normal within four weeks although animal models have shown that complete recovery of LV function and LV dilatation may not happen . StudiesIn conclusion, our patient presented with TIC after performing strenuous exercises for a few weeks. This condition can present in patients who perform strenuous exercises and in marathon runners. The condition is reversible, and patients show complete recovery with appropriate management of tachyarrhythmia. Most patients show recovery within two to three months and the biventricular function returns to normal. The condition is more commonly caused by supraventricular tachycardia than ventricular tachycardia. The key management strategy is antiarrhythmic medications, trigger avoidance, and rarely radio-frequency catheter ablation.