LV midwall fractional shortening (mwFS) was depressed in P-LFLG-AS vs. NFHG-AS  despite similar EF . By multiple regression, the presence of P-LFLG-AS remained a significant predictor of lower mwFS compared to NFHG-AS upon adjustment for cESS ; however, the significance was lost after further correction for LVd . In conclusion, the association of P-LFLG-AS with a lower cESS-adjusted mwFS, an index of afterload-corrected LV circumferential systolic function at the midwall level, appears secondary to a smaller LV end-diastolic cavity size according to the Frank–Starling law. Thus, low LV preload, not intrinsic contractile dysfunction or excessive afterload, may account for impaired LV circumferential midwall systolic performance in P-LFLG-AS.Paradoxical low-flow/low-gradient aortic stenosis (P-LFLG-AS) occurs in about one-third of patients with severe AS and preserved left ventricular (LV) ejection fraction (EF). Our aim was to differentiate between altered LV loading conditions and contractility as determinants of subtle LV systolic dysfunction in P-LFLG-AS. We retrospectively analyzed medical records of patients with isolated severe degenerative AS and preserved EF ), without relevant coexistent diseases  or any abnormalities which could account for a low-flow state. Patients with P-LFLG-AS and NFHG-AS did not differ in aortic valve area index and most clinical characteristics. Compared to NFHG-AS, subjects with P-LFLG-AS exhibited smaller LV end-diastolic diameter (LVd) (44 ± 5 vs. 54 ± 5 mm,  A considerable proportion (up to 50%) of patients with severe aortic stenosis (AS) do not meet the traditional criterion of transvalvular pressure gradient . Low-graAs shown by a meta-analysis of 18 studies including 7459 AS patients with preserved EF, mortality risk was higher in P-LFLG-AS compared to high-gradient AS and normal-flow/low-gradient AS ,4. ImporOur aim was to differentiate between altered LV loading conditions and contractility as determinants of subtle LV systolic dysfunction in P-LFLG-AS.2/m2 by the continuity equation) and EF ≥ 50% without relevant coexistent diseases and concomitant abnormalities [We retrospectively pre-screened the dataset of previously described patients with severe symptomatic degenerative AS  index ≤ 0.6 cmmalities ,11. Beyomalities ,11, exclmalities  or renalmalities .2 and mean aortic gradient < 40 mmHg) and 30 subjects with NFHG-AS (SV index ≥ 35 mL/m2 and mean aortic gradient ≥ 40 mmHg), corresponding to, respectively, stage D3 and D1 symptomatic severe AS, according to the current ACC/AHA guidelines on the management of valvular heart disease [A total of 60 patients entered the final analysis, including 30 subjects with P-LFLG-AS .Routine echocardiography during the index hospitalization had been performed by an experienced sonographer. From in-hospital echocardiographic records  and average in-hospital cuff systolic blood pressure, we calculated LV systolic performance and circumferential systolic wall stress at the midwall level as previously described, assuming a simplified cylindrical two-shell LV model ,15,16, sThe calculation of midwall fractional shortening (mwFS) enables avoiding an overestimation of fractional shortening with conventional endocardial measurements due to radial thickening, but not shortening, of longitudinal subendocardial fibers, especially in patients with concentric LV geometry ,15,16,17ac cycle ,15.In addition, mwFS was analyzed after adjustment for circumferential end-systolic LV midwall stress (cESS) which is directed along the same axis as systolic shortening of primarily circumferential midwall fibers, thereby providing a measure of the fundamental relationship between stress (an index of afterload) and shortening oriented in the same direction .mean is mean aortic pressure gradient (mmHg), 1.333 is a conversion factor from mmHg into hPa and all diameters are expressed in cm [Although commonly referred to as cESS, in the present study this measure of afterload was computed taking into account not only brachial systolic pressure but also mean transaortic pressure gradient, in agreement with an approach by Carter-Storch et al.  and Gerded in cm ,18,19  was derived from the mean aortic pressure gradient (APGmean), average in-hospital systolic blood pressure (SBP) and SV index using the following formula [In agreement with current clinical practice guidelines , EF was  formula ,25:Zva =equation ,25:SAC =Data are presented as mean ± standard deviation (S.D.) or numbers and percentages. Intergroup comparisons between P-LFLG-AS and NFHG-AS were performed using the 2-tailed Student’s t-test (or Welch test in case of variance inhomogeneity according to Levene’s test) or Fisher’s test for continuous and dichotomous variables, respectively. Forward stepwise ridge regression analysis was used to address the question of whether the association of P-LFLG-AS with lower mwFS compared to NFHG-AS could be attributable to different LV loading conditions, represented by cESS and LVd reflecting, respectively, afterload and preload .n = 30) and NFHG-AS subjects (n = 30) of 0.74 S.D.  at a type I error rate of 0.05.The study had a power of 80% to detect a mean difference in mwFS between P-LFLG-AS patients , Palo Alto, CA, USA).A Patients with P-LFLG-AS and NFHG-AS did not differ in most clinical characteristics and AVA index .In addition to decreased SV index and mean aortic gradient, subjects with P-LFLG-AS exhibited smaller LV size (consistent with low LV preload) with pronounced concentric remodeling compared to NFHG-AS . P-LFLG Upon forward stepwise ridge regression, the presence of P-LFLG-AS remained a significant predictor of lower mwFS compared to NFHG-AS after adjustment for cESS; however, the significance was lost after further correction for LVd .Our principal finding was the lack of significant load-independent differences in mwFS, an index of LV circumferential systolic function at the midwall level, between P-LFLG-AS and NFHG-AS. In particular, the association of P-LFLG-AS with lower mwFS corrected for cESS, an index of afterload, was abolished after further adjustment for a smaller LV diastolic dimension by an average of 10 mm, a surrogate measure of decreased preload in P-LFLG-AS versus NFHG-AS.max), but higher dp/dtmax normalized for lower LV end-diastolic volume  in P-LFLG-AS compared to NFHG-AS. That dp/dtmax is independent of afterload enables the separation of the effect of afterload from that of preload and intrinsic LV properties on LV performance. Notably, Eleid et al. [max in P-LFLG-AS and NFHG-AS; nevertheless, mean LVd was almost identical in their subjects with P-LFLG-AS and NFHG-AS. Accordingly, it can be hypothesized that a depressed mwFS at a comparable cESS in our P-LFLG-AS patients might rather be a consequence of inadequate LV preload (reflected by decreased LVd) than impaired LV contractility.Thirty years ago, in an experimental model of pressure-overload LV hypertrophy, Mirsky et al.  demonstrd et al.  reportedWe observed similar cESS, lower cESS-adjusted mwFS , increased Zva and diminished systemic arterial compliance in P-LFLG-AS vs. NFHG-AS. No significant intergroup differences in cESS despite a 1.7-fold higher Zva and 1.5-fold higher systemic arterial compliance might have reflected the impact of a smaller LV size and more concentric LV geometry which counterbalanced the effect of excessive arterial load on cESS in P-LFLG-AS. An increased Zva, especially its arterial component, is a typical feature of P-LFLG-AS , confirmAdmittedly, we did not assess longitudinal LV systolic function in our retrospective analysis of routine echocardiographic records. However, our findings are partially consistent with earlier noninvasive studies comparing P-LFLG-AS and NFHG-AS, including novel echocardiographic techniques. In particular, circumferential LV strain ,31,32,33Accordingly, these observations suggest a preferential impairment of LV longitudinal systolic function—not assessed in our study—in P-LFLG-AS, probably dependent on the long-time exposure of subendocardial cardiomyocytes to excessive wall stress with consequent supply–demand ischemia, apoptosis and fibrosis ,35,36. IAdditionally, it would also be interesting to analyze determinants of LV contractility in AS patients with reduced EF who had been excluded from the present study. Nevertheless, compared to patients with severe AS and normal LV contractility (by means of cESS-adjusted mwFS), those with depressed contractility and EF < 60% had similar both cESS and LVd, in contrast to AS subjects with EF ≥ 60% who exhibited lower cESS and decreased LVd (by about 7.5 mm) and concentric LV hypertrophy or remodeling in about 90% . These fNotably, these changes presumably develop before the onset of severe AS, being different in those with depressed and preserved EF. Ito et al.  reportedThese results highlight the relevance of avoiding excessive diuretic use and preventing bradycardia in order to optimize stroke volume and maintain adequate cardiac output in P-LFLG-AS.The dependence of depressed LV performance on low preload in P-LFLG-AS supports the concept of so-called preload stress echocardiography. P-LFLG-AS poses a diagnostic challenge because this condition requires multimodal imaging to differentiate true severe AS from pseudosevere AS, present in about one-third of patients with apparent P-LFLG-AS ,46. In aThe prognostic relevance of advanced indices of LV systolic performance is of clinical relevance. Depressed LV longitudinal strain was associated with adverse clinical outcome in AS ,39,40,41First, as our retrospective study was based on measurements performed on pre-recorded echocardiographic images from the index hospitalization, we had no opportunity to analyze LV systolic function along the longitudinal axis or to apply other advanced echocardiographic techniques. Notably, impaired longitudinal LV performance precedes circumferential dysfunction in AS ,37,43,44The association of P-LFLG-AS with lower cESS-adjusted mwFS, an index of afterload-corrected LV circumferential systolic function at the midwall level, appears secondary to a smaller LV end-diastolic cavity size according to the Frank–Starling law. Thus, low LV preload, not intrinsic contractile dysfunction or excessive afterload, may account for impaired LV circumferential midwall systolic performance in P-LFLG-AS.


Heart murmurs are a common finding in cats and, in many cases, the presence of an audible murmur on cardiac auscultation does not necessarily imply the presence of an underlying heart disease. Several studies have been published in the past to address the prevalence and clinical significance of heart murmurs in cats, but very few have looked into the exact origin of the blood flow turbulence responsible for this finding. We retrospectively reviewed clinical records and echocardiographic examinations of 856 cats with heart murmur and found that the majority of murmurs are caused by systolic anterior motion of the mitral valve (SAM) (39.2%) and dynamic right ventricular outflow tract obstruction (DRVOTO) (32%). These causes of murmur do not appear associated with a structural cardiac abnormality in 56.1% (SAM) and 85.0% (DRVOTO) of murmurs. This study also demonstrated that some heart murmur characteristics  can occasionally discriminate between normal cats and cats with underlying heart disease, with the exception of loud and palpable murmurs, which are inevitably associated with significant cardiac abnormalities. However, since the majority of heart murmurs in cats appear to be systolic and mild–moderate in loudness, echocardiography should always be considered following identification of a heart murmur on physical examination in cats.Background: Cardiac auscultation is one of the most important clinical tools to identify patients with a potential heart disease. Although several publications have reported the prevalence of murmurs in cats, little information is available in relation to the exact origin of the blood flow turbulences responsible for these murmurs. The aim of this study was to determine the prevalence and clinical significance of murmurs detected during physical examination in cats. Methods: Retrospective evaluation of clinical records and echocardiographic examinations performed in cats for investigation of heart murmurs; Results: Records of 856 cats with full clinical information were available for review. The cause of murmur was identified in 93.1% of cases . Systolic anterior motion of the mitral valve (SAM) was the primary cause of murmur in this population (39.2%), followed by dynamic right ventricular outflow tract obstruction (DRVOTO) (32%) and flow murmurs (6.9%). Most cats with a murmur (56.7%) did not present any structural cardiac abnormality. Conclusions: This study indicates that some heart murmur characteristics  can potentially predict the presence of an underlying cardiac disease. In people, heart murmurs are the most common reason for referral to a cardiologist and, especially in children, approximately 50–70% of these murmurs are clinically insignificant . SimilarTherefore, the main aim of this retrospective study was to determine the prevalence of heart murmurs detected during routine clinical examination in cats, with a particular emphasis on obtaining the exact echocardiographic identification of the origin of the flow turbulence deemed responsible for those murmurs. This study also sought to potentially identify patient and murmur characteristics that might predict a diagnosis of significant congenital or acquired cardiac disease.We hypothesized that the majority of cats with a heart murmur detected on cardiac auscultation do not have an identifiable cardiac abnormality on echocardiographic examination as previously observed in other studies ,3 and thClinical records and echocardiographic examinations performed on cats between June 2009 and June 2022 for diagnostic investigation of a heart murmur at 2 institutions, namely Specialist Veterinary Cardiology Consultancy  and The Ralph Veterinary Referral Centre , were reviewed retrospectively. The relevant information included examination date, cat’s signalment, heart murmur characteristics, echocardiographic identification of blood flow turbulence (single or multiple) associated with the detected heart murmur, echocardiographic measurements, presence of structural abnormalities, electrocardiographic (ECG) findings and whether or not the cat underwent sedation prior to the echocardiographic examination. Cats were excluded from the study if they had incomplete clinical information, including the full description of the detected heart murmur or if the full native echocardiographic examination was not available for review.Essential description of heart murmurs included timing , loudness/intensity  , point oAll echocardiographic examinations were performed by a board-certified cardiologist (LF) or a RCVS certificate holder in veterinary cardiology (HF) using an Esaote MyLab 30 Gold Cardiovascular or MyLab Omega  (SVCC Ltd.), or Esaote MyLab X8   echocardiographic machine and a 7.0–10.0 MHz or a 2.0–9.0 MHz phased array transducer depending on the size of the cat. All echocardiographic examinations were reviewed using dedicated offline ultrasound imaging software  to verify the correct identification of significant blood flow turbulence and confirm the final diagnosis.Complete transthoracic echocardiographic examination  was performed using routine echocardiographic views . All catSimultaneous ECG monitoring was obtained by applying non-traumatic ECG clips just above or below the elbows and just above or below the patella, using ultrasound gel as a conductive medium . WheneveLeft ventricular dimensions were measured from the right parasternal short axis view at the level of the papillary muscles using B-mode images from previously acquired high frame-rate cine-loops. For the purposes of this study, left ventricular hypertrophy was defined as a measurement of either interventricular septum in diastole (from leading to trailing edge) or left ventricular free wall in diastole (from leading to leading edge) greater than 6.0 mm, avoiding prominent false tendons, focal myocardial thickening at their insertion or punctual hyperechogenicity ,12. LeftDiagnosis of SAM was characterized by the concurrent presence of motion of the septal mitral valve leaflet towards the interventricular septum during systole, observed on a right parasternal short-axis M-mode view of the left ventricle at the level of the mitral valve, turbulent flow in the left ventricular outflow tract with simultaneous mitral regurgitation in mid-systole systole  and a dagger-shaped (scimitar-like) flow profile on spectral Doppler interrogation of the left ventricular outflow tract ,14,15,16The presence of DRVOTO was confirmed as systolic color Doppler aliasing in the right ventricle (RV) just cranial to the tricuspid valve and extending into the RV outflow tract, associated with spectral dispersion and a scimitar-like appearance of the RV outflow profile on spectral Doppler study, as previously described ,19. InduDiagnosis of flow (often named “innocent”) heart murmurs was based on the absence of any detectable structural or functional abnormalities on echocardiographic examination, despite the presence of a soft heart murmur on auscultation ,21.Mitral valve and tricuspid valve regurgitation were diagnosed following identification of a systolic turbulence directed towards the left and right atrium, respectively. The valvular regurgitation was confirmed in the left apical view using spectral Doppler interrogation of the abnormal flow. Conversely, mitral valve stenosis was diagnosed by demonstrating a diastolic turbulence directed towards the left ventricle and a typical prolonged deceleration time of the E wave on spectral Doppler inflow studies .Mid-left ventricular outflow obstruction, also called mid-cavitary outflow obstruction, was defined as a systolic turbulent flow originating at the middle of the left ventricle as a result of segmental mid-septal hypertrophy and misplacement of the papillary muscles and chordae tendineae in cats with left ventricular hypertrophy ,24.Pulmonic stenosis (PS) and aortic stenosis (AS) were deemed to be valvular unless otherwise stated and were confirmed by identification of partially fused cusps and increased systolic blood flow across the pulmonic and aortic valve respectively. Sub-aortic stenosis and supravalvular aortic stenosis were diagnosed after identification of a systolic blood flow turbulence in correspondence of a membrane just below or above the aortic valve respectively, causing a fixed obstruction. Double-chambered right ventricle (DCRV) was diagnosed when the blood flow turbulence and associated increased flow velocity was originating from a mid-cavitary obstruction dividing the right ventricle into a high-pressure proximal portion and a low-pressure distal portion. Aortic insufficiency (AI) was diagnosed after identification of a significant diastolic flow from the aorta towards the left ventricular cavity, mostly associated with aortic valve endocarditis or aortic valve dysplasia ,26.Heart murmurs associated with VSD and ASD were diagnosed following visualization of an incomplete septum and identification of a systolic flow turbulence across the defect .Blood flow turbulence associated with tetralogy of Fallot was characterized by a combined pulmonic stenosis and right-to-left shunting VSD .Diagnosis of patent ductus arteriosus (PDA) was based on the identification of the ductus arteriosus and an associated continuous blood flow turbulence across the defect directed toward the main pulmonary artery, since all PDAs in this cohort were left-to-right shunting .The blood flow turbulence associated with atrioventricular canal defect, also called cushion defect, was mainly characterized by a systolic shunt of the blood passing from the left ventricle to the right ventricle and out the pulmonary artery .Heart murmur in coronary artery to pulmonary artery fistula was associated with a continuous left-to-right blood flow turbulence across the abnormal vascular communication .Collected data were transferred to an electronic spreadsheet  and verified by 3 investigators  for accuracy. Quantitative variables were analyzed for normal distribution using the Shapiro–Wilk test and subsequently reported as mean ± standard deviation if normally distributed or median and range if non-normally distributed. Qualitative variables were summarized using absolute and relative frequencies.To test the hypothesis that in the majority of cats with a heart murmur detected on cardiac auscultation the murmur was not associated with a structural cardiac disease, we simply calculated the percentage of cats with a heart murmur without echocardiographic evidence of structural heart abnormalities.p value of <0.05 was considered to be statistically significant. All statistical analysis was performed with a commercially available statistical program .Univariable logistic models were used to test the hypothesis that patient signalment  and heart murmur characteristics  can predict the presence of a structural cardiac dis-ease. For this purpose, cat’s age, gender, breed as well as heart murmur characteristics were assessed as categorical variables, and murmur intensity was reclassified as “soft” (grade 1/6 or 2/6), “moderate” (grade 3/6), “loud” (grade 4/6) or “palpable” (grade 5/6 and 6/6), following the scheme proposed by Rishniw in 2018. This system is described as a simpler and more intuitive grading scheme that should provide the same clinical information as that obtained with the more complex Levine scheme but with potentially less confusion -phenotype) were 6 months old and, in both cases, the echocardiographic changes were associated with suspected acute myocarditis, which was followed by a complete reverse cardiac remodeling (confirmed on repeat echocardiographic examination) after a few weeks and complete disappearance of their heart murmur.Systolic anterior motion of the mitral valve (SAM) was the most common cause of heart murmur identified in this feline population (39.2%), followed by dynamic right ventricular outflow tract obstruction (DRVOTO) (32%) and flow murmurs (6.9%). All different causes of blood flow turbulence responsible for heart murmurs in this feline population are reported in n = 485; 56.7%). These were mainly cases where the blood flow turbulence was associated with SAM (50.3%), DRVOTO (19.9%) and flow murmurs (14.6%). However, when these types of murmurs were analyzed individually as a sole cause of murmur, 56.1% of cats with SAM and 85.0% of cats with DRVOTO did not display any structural cardiac abnormalities on echocardiographic examination. None of the cats with flow murmurs had structural abnormalities, by definition. Most cats with DRVOTO were older individuals, with a median age of 9.3 years .The majority of cats that underwent full echocardiographic examination to identify the cause of a previously detected heart murmur did not present any structural cardiac abnormality  or acquired cardiac conditions (29.3%), with a relative frequency depending on the underlying condition, as reported in Physical characteristics of the cats  and heart murmur characteristics  were analyzed using univariable and multi-variable logistic regression analyses to assess the probability of identifying a structural heart disease on echocardiography. All palpable, continuous, diastolic and to-and-fro murmurs were associated with a significant congenital cardiac disease (100%). Conversely, a negative association was found between soft/moderate systolic heart murmurs, intermittent heart murmurs, murmurs with a PMI over the right parasternal area and the presence of a cardiac abnormalities on echocardiography .A group of cats with an audible heart murmur on cardiac auscultation did not reveal any significant blood flow turbulence on echocardiographic examination until a provocative maneuver was performed and such murmurs were classified as inducible heart murmurs . These were characterized by inducible DRVOTO (8.3%) and inducible SAM (2.6%). In more detail, a provocative maneuver was necessary to reveal DRVOTO in 20.3% of cats and SAM in 5.1% of cats, respectively.To the best of the authors’ knowledge, this is the largest and most comprehensive study looking into the etiology and clinical characteristics of heart murmurs in cats and, unlike most of the published research on feline heart murmurs, is the first attempt to systematically identify the precise origin of the blood flow turbulence responsible for these murmurs.The median age and body weight of cats referred to our clinics for cardiac investigation were very similar to other studies performed in cats referred to a cardiologist for further cardiac investigations ,6.The majority of murmurs detected on auscultation were systolic, soft or moderate and with a PMI over both parasternal areas  with no apparent association with the underlying heart murmur etiology or the severity of the underlying heart condition. This suggests that heart murmur characteristics in the majority of cats may have a limited diagnostic relevance, although loudest murmurs are more likely associated with a pathological condition, mainly severe congenital cardiac defects, as previously reported . The sigEchocardiographic identification of the blood flow turbulence responsible for the detected heart murmur was obtained in 93.1% of cases. In the remaining 6.9% of cases, echocardiographic examination failed to identify any significant turbulence or structural abnormality, which led to an echocardiographic diagnosis of flow (innocent) murmurs, adopting the same diagnostic criteria described in humans ,21.Approximately one quarter of cats had multiple blood flow turbulences identified on echocardiography, which were deemed responsible for the murmur detected on auscultation. This is, in our opinion, another important finding that reinforces the above observation that detection of heart murmurs in cats, in the absence of an echocardiographic examination, cannot provide sufficient information towards an etiological diagnosis, with the exception of intermittent heart murmurs inducible by chest compression and unmasked by varying the pressure of the stethoscope on the chest wall  or heartUnlike other studies where heart murmurs in cats appeared to be mostly associated with a cardiac disease ,3,5,7, tThe most common origin of heart murmurs in these cats was dynamic left ventricular outflow obstruction associated with SAM, which represents approximately 40% of all murmurs detected in this feline population. Eighty percent of cats with HCM-phenotype and a heart murmur on auscultation had SAM. Systolic anterior motion of the mitral valve was also present in other forms of cardiomyopathy, such as in 27.3% of restrictive cardiomyopathy (RCM)-phenotype, 33.3% of non-specific cardiomyopathy and 22.2% of end-stage HCM, based on the classification proposed by Luis Fuentes et al. ,14.The second most common cause of heart murmur in this feline population was represented by a dynamic right ventricular outflow tract obstruction (DRVOTO), which was identified in approximately one third of cases. DRVOTO did not seem to be associated with any cardiac disease in 85.0% of cases, and since the echocardiographic abnormalities observed in the remaining 15.0% of cases did not appear to affect the right outflow tract, we believe that the presence of DRVOTO in such cases represents a pure incidental finding.Flow (Innocent) heart murmur represented the third most common cause of murmurs in this study (6.9%). However, it may be possible that the number of innocent murmurs was overestimated since a provocative maneuver was not performed in all echocardiographic examination to reveal the presence of inducible SAM or iatrogenic DRVOTO . It is aBlood flow turbulences associated with various congenital defects were considered responsible for an audible heart murmur in the remaining 21.9% of cases. However, it was impossible from our data to establish whether ASDs were responsible for an audible heart murmur since they were always associated with other significant blood flow turbulences.The importance of this finding is particularly relevant for the clinical management of these cases, where an early diagnosis may change the clinical outcome by prompting corrective or palliative interventions  or regular monitoring of the sleeping respiratory rate to allow early identification of clinical signs associated with congestive heart failure ,35.Owing to the retrospective nature of this study, some data were missing in a number of patients, including blood pressure measurement, hematocrit and serum concentrations of thyroxine hormone, which may have had a potential impact on the genesis of the heart murmurs. Given the lack of data on systemic status of cats, it is not possible for the authors to conclusively exclude that, at least in some patients, the actual main or concurrent trigger of the murmur could have been misdiagnosed.Another limitation was the inability to determine if outflow obstructions (namely SAM and DRVOTO) could have been potentially induced in some cases of “innocent” murmurs since the provocative maneuvers explained above were not always performed, especially when these techniques were still unknown or poorly described. Furthermore, limited characterization of the type of murmur for each echocardiographic abnormality may also represent a possible bias.Another potential limitation is represented by the unknown effect of the various sedative protocols on the structural and functional echocardiographic findings, although a relatively small percentage of cats were sedated in this study. Similarly, information about the use of cardioactive drugs was missing in many cases, and therefore it was not possible to analyze their effect on the clinical and echocardiographic findings. Finally, different clinicians were involved in the diagnosis and management of cats included in this study and this could have affected the accuracy of the results, although all clinical records and echocardiographic examinations were retrospectively reviewed by a board certified cardiologist to double-check the accuracy of measurements and diagnoses.More than half of cats referred for a cardiac evaluation of an audible heart murmur on thoracic auscultation do not have any echocardiographic evidence of heart disease, suggesting that most heart murmurs in cats are benign or may be potentially associated with a subclinical form of heart disease not detectable echocardiographically. This study also demonstrates that some heart murmur characteristics  can occasionally discriminate between normal cats and cats with underlying cardiac disease, with the exception of loud (mostly systolic) and palpable murmurs inevitably associated with a significant heart disease. However, since the majority of heart murmurs in cats appear to be systolic and mild-moderate in loudness, echocardiography, ideally performed by an experienced cardiologist, should always be considered following identification of a heart murmur on routine physical examination in cats, especially when they do not present any clinical signs referable to a heart disease.


We compared the safety, efficacy, and composite outcome  at 3 years post-implant between the snare and conventional groups. In the snare group, all LV leads were implanted safely using orthodromic (n = 15) or antidromic (n = 5) techniques, and no immediate complications occurred including vessel perforation, tamponade, and lead dislodgement. During follow-up, LV lead threshold and impedance remained stable without requiring lead revision in the snare group. There were no significant between-group differences regarding LV ejection fraction increase  and LV end-systolic volume reduction . Both groups exhibited comparable CRT-response rates . The risk of primary outcome was not significantly different between the two groups . In patients who failed conventional LV lead implantation for CRT, the snare technique could be a safe and effective solution to overcome difficult coronary venous anatomy.The snare technique can be used to overcome unsuitable cardiac venous anatomies for left ventricular (LV) lead implantation in cardiac resynchronization therapy (CRT) procedures. However, limited data exist regarding performance of the snare technique. We classified 262 patients undergoing CRT procedure into the snare ( Cardiac resynchronization therapy (CRT) has demonstrated prognostic benefits in patients with systolic dysfunction and ventricular dyssynchrony ,2,3, andAmong the various techniques, Worley et al. first reported the LV lead implantation technique using a goose neck snare in patient with stenosis at the target vein ostium . They adn = 10) or died during index admission (n = 4). Finally, a total of 262 patients were selected for the current study. According to the method of LV lead implantation, patients were classified into the snare technique group (n = 20) and the conventional method group (n = 242) (We enrolled 276 consecutive patients who underwent CRT (de novo or upgrade) for advanced heart failure (HF) at our institution between May 2014 and December 2021. All enrolled patients had LV ejection fraction (LVEF) ≤35% on transthoracic echocardiography, QRS duration ≥120 msec on 12-lead electrocardiogram (ECG), and New York Heart Association functional class II, III, or ambulatory IV despite guideline-directed optimal medical treatment for at least 3 months. We excluded patients who had undergone epicardial LV lead insertion (n = 242) . The insCRT devices were implanted under local anesthesia using a transvenous approach . For conThe snare technique was tried when conventional LV lead implantation failed due to anatomical difficulties including great tortuosity, stenosis, small diameter, or ostial dissection of target veins. Additional venography was performed in a super-selected side branch using 4 or 5 Fr vein selectors  to evaluate the presence of collateral/connecting vessels between the target and nearby veins. Two kinds of snare technique, orthodromic and antidromic, were performed, similar to the methods described by Worley et al. . The ‘orMore specifically, in the orthodromic snare technique, the 0.014″ guidewire was advanced antegrade into the target vein and then back into the CS ostium via collateral/connecting vessels. Then, the guidewire was snared around the CS ostium using an Amplatz Goose Neck snare  or EN Snare . The snares were usually introduced via the sheaths prepared for insertion of the right atrial or right ventricular leads. The snared distal end of the guidewire was pulled out of the sheath. Using a veno-venous loop, the LV lead was inserted at the proximal end of the guidewire and then advanced into the target vein along the guidewire, while the distal end of the guidewire was under the control of the operator  were assessed by the biplane Simpson’s method. Medical treatments for advanced HF were performed based on current guidelines .The primary composite outcome included all-cause death and HF readmission. Secondary outcomes were cardiac death, left ventricular assist device implantation, heart transplantation, LV lead dislodgement or failure, and individual components of the primary outcome. All deaths were considered to be cardiac deaths unless a definite noncardiac cause could be established. All end points in this study were censored at 3 years after the index procedure. The mean follow-up duration of the study population was 22.6 ± 19.9 months. The definitions of CRT responders were as follows: (1) ‘responder’ for patients with LVEF improvement from baseline ≥10% or LVESV reduction from baseline ≥15% and (2) ‘super-responder’ for patients with LVEF improvement from baseline ≥20% or LVESV reduction from baseline ≥30%.t-test or the Mann–Whitney rank-sum test and presented as mean and standard deviation according to distribution, which was assessed by the Kolmogorov–Smirnov test and visual inspection of Q-Q plots. All discrete or categorical variables were presented as number and relative frequency (percentage) and compared using the chi-squared test or Fisher’s exact test. In comparing follow-up echocardiography and ECG parameters between the snare and conventional groups, we analyzed the most recent results within 3 years of the index procedure. LV lead pacing threshold and impedance were compared at baseline and 3, 6, 12, and 24 months between the two groups.Continuous variables were analyzed using unpaired The cumulative incidence of primary outcome was presented as Kaplan–Meier estimate and compared using a log-rank test or Breslow test. Multivariable Cox proportional hazard regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) to compare the risk of clinical events between the snare group and the conventional group. Multivariable Cox proportional hazard models were constructed using variables that were potentially clinically relevant: age, baseline LVEF, and baseline LVESV.p < 0.05. Statistical analyses were performed using SPSS 25.0 for Windows , and R version 3.6.0 .All analyses were two-tailed, and statistical significance was defined as Among a total of 262 patients, the snare technique was used in 20 and the remaining 242 underwent CRT implantation without snare. Demographics, cardiovascular risk factors, and initial ECG findings including atrial fibrillation, left bundle branch block, and QRS duration were not significantly different between the snare and conventional groups . The conn = 11), stenotic/small-sized (n = 7), or dissected target veins (n = 2). All LV leads were deployed successfully in the lateral LV walls using orthodromic (n = 15) or antidromic snare technique (n = 5). Five antidromic snare cases were performed due to failure of antegrade-wiring into the tortuous target vein (n = 3) or target vein dissection that occurred during the conventional approach (n = 2). The mean procedure time for overall rescue CRT procedure using the snare was 178 ± 70 min. The mean procedure time tended to be longer in the snare group than in the conventional group . However, the mean procedural time of the snare group decreased with increasing experience with the snare technique   . EventuaDuring long-term follow-up, the LV lead pacing threshold of the snare group slightly increased at 3 months but then remained stable and well-maintained around 2.0 V at 0.4 ms. The LV lead pacing thresholds were not significantly different between the snare and the conventional groups at baseline or 3, 6, 12, and 24 months after the procedure . The LV p = 1.000 and 37.5% vs. 42.3%, p = 0.915, respectively). The detailed follow-up electrocardiographic and echocardiographic parameters of the snare group are presented in Follow-up QRS duration and QRS narrowing from baseline were not significantly different between the two groups . There wp = 0.817)  . FurtherIn the present study, we evaluated the feasibility of the snare technique compared with the conventional method for LV lead implantation in CRT procedure. The major findings were as follows. First, no immediate complications including vessel perforation, pericardial effusion, cardiac tamponade, or lead dislodgement or malfunction occurred in the snare group. Second, in the snare group, the LV lead pacing threshold and impedance remained stable and well-maintained without requiring lead revision during long-term follow-up. Third, the snare group showed comparable electrocardiographic and echocardiographic responses to those of the conventional group. Fourth, there was no significant difference in the risk of primary composite outcome between the snare and conventional groups.CRT has become a standard treatment in patients with ventricular systolic dysfunction and dyssynchrony by restoring atrioventricular, inter- and intra-ventricular synchrony . PositioTo date, various tools and techniques have been developed to overcome difficult coronary venous anatomy ,15. The Our study has several limitations. First, because the number of enrolled patients, especially in the snare group, was small, the study lacked adequate power to compare outcomes between the groups. The potential bias can influence the study outcome. Therefore, our results should be interpreted carefully. Second, the snare technique is only applicable in patients with connecting vessels between the target and nearby veins. When the rescue snare technique cannot be attempted due to lack of collateral/connecting vessels, epicardial lead implantation or conduction system pacing is an alternative for failed conventional CRT procedures. Third, CRT response is primarily determined by the final LV lead position rather than the lead implantation technique. In the present study, electromechanical CRT response and clinical outcomes were not significantly different between the snare and the conventional groups. It suggests that LV leads were properly positioned at the target area by the snare technique, although the patients had difficult coronary venous anatomy. Fourth, the snare group showed larger baseline LVEF and smaller baseline LVESV than the conventional group. Although we performed adjustments to overcome the potential bias by differences in baseline echocardiographic findings, the remaining bias might have affected study outcomes.In patients who failed conventional LV lead implantation for CRT, the snare technique could be a safe and effective solution to overcome difficult coronary venous anatomy. Long-term performance of the LV lead implanted using the snare technique was well maintained without dislodgement. Furthermore, the snare technique showed comparable clinical and electromechanical CRT outcomes to those of the conventional method during long-term follow-up. Therefore, to maximize long-term CRT outcomes, the snare technique should be more aggressively considered for implanting the left ventricular lead at the optimal target site in patients with difficult anatomical barriers.


In atrial and ventricular tachyarrhythmias, reduced time for ventricular filling and loss of atrial contribution lead to a significant reduction in cardiac output, resulting in cardiogenic shock. This may also occur during catheter ablation in 11% of overall procedures and is associated with increased mortality. Managing cardiogenic shock and (supra) ventricular arrhythmias is particularly challenging. Inotropic support may exacerbate tachyarrhythmias or accelerate heart rate; antiarrhythmic drugs often come with negative inotropic effects, and electrical reconversions may risk worsening circulatory failure or even cardiac arrest. The drop in native cardiac output during an arrhythmic storm can be partly covered by the insertion of percutaneous mechanical circulatory support (MCS) devices guaranteeing end-organ perfusion. This provides physicians a time window of stability to investigate the underlying cause of arrhythmia and allow proper therapeutic interventions . Temporary MCS can be used in the case of overt hemodynamic decompensation or as a “preemptive strategy” to avoid circulatory instability during interventional cardiology procedures in high-risk patients. Despite the increasing use of MCS in cardiogenic shock and during catheter ablation procedures, the recommendation level is still low, considering the lack of large observational studies and randomized clinical trials. Therefore, the evidence on the timing and the kinds of MCS devices has also scarcely been investigated. In the current review, we discuss the available evidence in the literature and gaps in knowledge on the use of MCS devices in the setting of ventricular arrhythmias and arrhythmic storms, including a specific focus on pathophysiology and related therapies. Ventricular arrhythmias are responsible for a significant number of sudden cardiac deaths (SCD) . ImplantHeart failure with reduced ejection fraction is burdened with a higher risk of SCD and poor prognosis. Left ventricular ejection fraction (LVEF) has been recognized as the strongest predictor of ventricular arrhythmias and mortality in patients with cardiomyopathies , and it Catheter ablation (CA) of ventricular tachycardia (VT) represents a percutaneous technique that can permanently treat VT and prevent its recurrence. Current expert consensus recommends using CA for recurrent VT refractory to antiarrhythmic therapy or in those who tolerate antiarrhythmic drugs poorly . PreprocPatients requiring CA for ventricular arrhythmias may present with structural heart disease, commonly ischemic heart disease. In such a clinical scenario, acute hemodynamic decompensation during the CA procedure is not uncommon, affecting 11% of patients and is associated with an increased mortality rate . In addiMechanical circulatory support (MCS) devices, such as Impella and venoarterial extracorporeal membrane oxygenation (VA ECMO), may represent an appealing tool to support blood pressure and guarantee adequate end-organ perfusion during the CA of VT. However, MCS implantation carries its own costs and intrinsic risk of complications, mainly related to bleeding and vascular complications , 14. Foret al. analyzed the available evidence regarding the use of temporary MCS in life-threatening arrhythmias with interesting conclusions about the application of the PAINESD risk score, as further discussed, and the prophylactic use of VA ECMO for an electrical storms  is determined by the heart rate (HR) and by the stroke volume (SV) of the left ventricle (LV). The latter is the difference between end-diastolic (EDV) and end-systolic volume (ESV).* SVCO = HR SV = EDV – ESVFrom the first equation, it is easy to understand that (extreme) bradycardia will lead to decreased cardiac output and eventual low-output cardiogenic shock (CS) . In paraAcute sustained bradycardia is most frequently related to hypoxia , conductThe most frequent malignant tachyarrhythmia is ischemia-induced sustained VT, which can result in ventricular fibrillation (VF), SCD, or CS. VT can be related to a new onset acute myocardial infarction or rising from scar tissue from a previous insult . Lethal In a normal cardiac cycle, the LV overcomes the diastolic blood pressure during the isovolumetric contraction phase until the aortic valve opens and the intraventricular blood gets ejected .This drop in the native cardiac output during an arrhythmic storm can be partly covered by the insertion of a percutaneous mechanical circulatory support device , which offers a continuous forward flow of blood from the LV into the aorta. This flow is both afterload sensitive, with end-organ perfusion increasing with lower systemic vascular resistance, and preload dependent, requiring sufficient volume from the right ventricle to operate effectively. If the failing LV can no longer overcome afterload in the new equilibrium of increased mean arterial pressure and reduced preload created by the continuous flow of the percutaneous MCS device, the arterial trace will flatten. This process is called ventriculoarterial uncoupling  28)..28).Bradycardia-induced CS can often be reversed by positive chronotropic agents or urgent temporary (ventricular) pacing, which leaves physicians a time window for diagnosing and resolving the underlying cause.Management of patients with CS shock and (supra) ventricular arrhythmias is particularly difficult. Inotropic treatment, such as dobutamine, is recommended for CS but may exacerbate supraventricular tachycardia or accelerate the heart rate in these patients. Antiarrhythmic drugs  often have negative inotropic effects and may exacerbate the CS state. Electrical reconversions often risk worsening circulatory failure or cardiac arrest in these critically ill CS patients. Therefore, urgent implementation of MCS devices can be an effective way of stabilizing CS patients and allowing physicians a time window of stability to investigate the underlying cause of the arrhythmia and allow therapeutic interventions  . The fieLeft ventricular assist devices (LVADs) are used to support a failing heart as a temporary means (bridge to recovery and bridge to transplant) or as destination therapy. The interaction between reduced native cardiac function and continuous flow generated by LVAD creates a complex interplay, which may impact the restoration of LV performance.in vitro study by Viola et al. confirmed how LVAD flow affects intraventricular hemodynamics and pressure. Indeed, the unloading of LV generated by LVAD causes a reduction in ventricular peak systolic pressure, which is related to LVAD output  in patients who received pre-emptive insertion of percutaneous LVAD (Impella) compared to patients undergoing rescue insertion of MCS .Although the evidence is still scant, the clinical rationale for preemptive implantation of temporary MCS during high-risk CA of VT is strong. The adequate timing of temporary MCS implantation for high-risk patients  undergoing CA of VT is still under debate. However, it is evident that this aspect is of pivotal importance given the high mortality rate of patients requiring emergent implantation of MCS during CA procedures. For this reason, it is crucial to identify, before the procedure, those patients who may experience acute hemodynamic deterioration during the CA of VT.In 2015, Santangeli et al. studied the prevalence and predictors of periprocedural acute hemodynamic decompensation in patients undergoing radiofrequency CA for scar-related VT. In this study, almost one out of 10 patients experienced hemodynamic instability, impacting mortality. The authors identified eight clinical factors predicting periprocedural acute hemodynamic decompensation (PAINESD risk score): advanced age, chronic obstructive pulmonary disease, use of general anesthesia, ischemic cardiomyopathy, heart failure (NYHA classes III and IV), lower LV ejection fraction, presentation with VT storm, and diabetes mellitus .p-value = 0.02]. Conversely, patients with a predicted low risk of acute hemodynamic decompensation did not experience any benefit   0.43; 95% confidence interval (CI) 0.21–0.87;  = 0.35) .robust tool to identify high-risk patients who might benefit from temporary prophylactic MCS during electrophysiological studies.” They suggested a PAINESD cut-off score of 15 for considering preemptive implantation of temporary MCS, particularly if prolonged VT mapping is required or long phases of unstable VT are expected  or no mechanical support .One year later, Bunch et al. analyzed a cohort of high-risk patients with hemodynamically unstable VT undergoing CA guided by activation and entrainment mapping and assisted by Tandem Heart. Despite longer procedure times, the outcomes of acute complications (including death and stroke) and freedom from ICD or therapies for sustained VT were comparable to a matched cohort undergoing substrate mapping without temporary MCS .In a retrospective study, Aryana et al. demonstrated a shorter total radiofrequency ablation time for patients receiving percutaneous LVAD for CA of unstable VT compared to procedures without MCS. That was accompanied by a reduced length of hospital stay . The subDespite the differences found in diverse case series, the long-term follow-up did not reveal any statistically significant difference in rates of VT recurrence between patients undergoing CA with and without temporary MCS , 40. TheIn the context of hemodynamically tolerated ventricular arrhythmias, the substrate-based CA strategy has proven to have similar acute procedural efficacy and VT recurrence compared with activation and entrainment mapping, with a comparable rate of complications and mortality . For thoDifferent devices, from IABP to VA ECMO, have been proposed as hemodynamic support during CA procedures, thus further increasing the variability between the studies. Each MCS device can guarantee a different level of cardiovascular assistance. Unfortunately, only a few studies have addressed the specific issue of direct comparison between MCS devices.IABP was proven less effective in providing hemodynamic support than percutaneous LVAD (Impella 2.5) during CA for VT. In a multicentre study, Reddy et al. found that implantation of Impella or Tandem Heart facilitated activation and entrainment mapping of several unstable VTs with fewer rescue shocks compared to patients supported with IABP . A retroImpella and Tandem Heart have specific contraindications to their implantation: LV thrombosis, mechanical aortic valve replacement, and ventricular septal defect. These contraindications must be considered when choosing a temporary MCS device. Furthermore, these two devices are burdened with technical limitations related to the requirement of transeptal puncture for Tandem Heart and electromagnetic interference during mapping for Impella .VA ECMO can provide both biventricular and respiratory support, thus allowing its use in extreme conditions of hemodynamic instability, such as cardiac arrest, and as a bridge to recovery or heart transplantation , 43. ComGiven its unparalleled capacity to provide end-organ perfusion, VA ECMO represents a useful solution for hemodynamic support in adult patients presenting with electrical storm, VT refractory to antiarrhythmic therapy, and recurrent VF. The combination of hypotension due to refractory VT/VF, cardiac stunning related to repeated shocks, and the frequent requirement for sedation/anesthesia during CA for VT/VF arrhythmic storms may precipitate acute hemodynamic decompensation . In the VA ECMO is the most commonly used temporary MCS device as a rescue strategy for cardiovascular support in children requiring radiofrequency ablation for tachycardia-induced cardiomyopathy , 46, forPermanent ventricular assist devices (VADs) represent a therapeutic option for end-stage heart failure as a bridge to heart transplantation or even as “destination therapy” . The repLin et al. have addressed the role of ventricular arrhythmias in patients with biventricular assist devices (BIVAD) in a retrospective cohort study . The prePatients with CS refractory to inotropic agents and vasopressors have a poor prognosis, and the VA ECMO offers the ability to restore hemodynamics and prevent end-organ damage. Time to decision and time to initiate VA ECMO is crucial. A narrow “window of opportunity” for rescue VA ECMO intervention exists, beyond which a patient may develop hypoperfusion brain damage, multiorgan failure, reperfusion sepsis, and is too ill to benefit from a temporary MCS .cor pulmonale.The applications of the VA ECMO in life-threatening arrhythmias encompass arrhythmogenic storm triggered by cardiac ischemia, fulminant myocarditis with ventricular arrhythmias, periprocedural in the cath-lab, accidental hypothermia, and some poisonings  . Right vIn a patient younger than 70 years with cardiac arrest, an ideal therapeutic window for a VA ECMO start  is within 40 min from the witnessed collapse. The maximum associated delay with acceptable rates of cerebral performance score (CPS) 1–2 is up to 60 min. Crucial is decision-making at 10–15 min of refractory cardiac arrest. That also relates to the expected transfer to the facility or the ECMO to the scene and percutaneous cannulation times of ~14–20 min  trial. The investigators reported rates of survival to hospital discharge up to 60% among recipients of ECMO after in-hospital cardiac arrest (IHCA), especially when related to cardiac etiology (p < 0.0001) (ECMO has demonstrated its impact on outcomes of cardiac arrest and CS . The suretiology . Acute m 0.0001) . ECMO yiThe use of VA ECMO during periprocedural arrhythmia is increasing. A substantial mortality benefit was observed among high-risk patients identified with a PAINESD risk score or suffering from electrical storm and treated with preemptive temporary MCS . The patSevere accidental hypothermia is associated with ventricular arrhythmias –69, and 2 production  with decreasing blood flow and lower sweep gas flow. These are related to an early afterload effect on the heart recovering from hypothermia and hypothermia-related low COoduction .The cannulation should not interfere with the CA techniques if inserted as periprocedural support with a femoro-femoral approach, representing the desirable configuration for periprocedural support or during ECLS.In all the settings, the return arterial cannula may frequently block the distal leg perfusion, which is, in most centers, solved by routine cannulation of the prograde 6–7F vascular sheath into the superficial femoral artery. The insertion should be as close to the ECMO return cannula as possible because the no-flow segment between them soon becomes a site of thrombus formation.A minimum cardiac output of 1–2 l/min should be maintained even in circulatory failure supported by the VA ECMO, which would secure LV unloading and prevent intracardiac thrombus formation. If this is not possible, the available methods of unloading are Impella, a surgical vent of the LV either through the mitral valve and left atrial auricle or transseptal approach, or to a certain degree, also with the IABP , 73.Details regarding VA ECMO configuration, hemodynamics, and complications are beyond the scope of the current review and are detailed elsewhere.As detailed above, MCS is an effective strategy to rest the heart and support the circulation when it is compromised by ineffective cardiac contraction during an arrhythmic storm. Although sinus rhythm may be restored after the initiation of VA ECMO in the ECLS setting, intractable ventricular arrhythmias may persist despite full circulatory support. In a recent publication of patients treated with MCS during arrhythmic storm, no differences between survivors and non-survivors were noted according to the use of antiarrhythmic drugs  .The percutaneous blockade of the stellate ganglion has been described in different populations, including in patients with electrical storm on MCS. It is a minimally invasive (either blind or ultrasound-guided) technique that has been demonstrated to relieve ventricular arrhythmic burden in a remarkable rate of patients when all other pharmacological therapies failed without serious complications –77.Large studies have reported an overall prevalence of arrhythmias after SARS-CoV-2 infection that ranges from 10 to 20%, although the incidence is greatly increased in individuals with severe disease. Arrhythmias are supraventricular in most of the critically ill patients with COVID-19. However, 40% of the overall arrhythmias are ventricular tachyarrhythmias, bradyarrhythmias, and conduction defects, which are associated with remarkably high mortality .via several mechanisms, including complex modulatory activities on the expression and function of specific ion channels and gap junction-forming connexins, cytochrome system inhibition, and structural remodeling by activating the myofibroblast-driven synthesis of extracellular matrix responsible for cardiac fibrosis , from which the publication fees have been provided.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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A proportion of patients with the acute coronary syndrome (ACS) will suffer progressive remodeling of the left ventricular (LV). The aim was to screen for important biomarkers from a large-scale protein profiling in 420 ACS patients and define biomarkers associated with reduced LV function early and 1 year after the ACS. Transferrin receptor protein 1 and NT-proBNP were associated with LV function early and after 1 year, whereas osteopontin and soluble ST2 were associated with LV function in the early phase and, tissue-type plasminogen activator after 1 year. Fatty-acid-binding protein and galectin 3 were related to worse GLS but not to LVEF 1 year after the ACS. Proteins involved in remodeling and iron transport in cardiomyocytes were related to worse LV function after ACS. Biomarkers for energy metabolism and fibrosis were exclusively related to worse LV function by GLS. Studies on the functions of these proteins might add knowledge to the biological processes involved in heart failure in long term after ACS.The online version contains supplementary material available at 10.1007/s12265-022-10285-2. In acute coronary syndrome (ACS), assessment of the left ventricular (LV) function is included in risk evaluation of the patients and forms the base for recommendation of medical treatment and device therapy with intracardiac defibrillator . EchocarIn chronic heart failure and also in healthy elderly individuals, several circulating biomarkers have been evaluated as predictors of heart failure hospitalization and mortality –16. N-teThere are limitations of LVEF as the only measurement of LV function since it is based on an endocardial measurement and influenced by geometry . Global The REBUS  study was a prospective observational study previously published  . Briefly96x96 proximity extension assay , at the Clinical Biomarkers Facility, Science for Life Laboratory, Uppsala University, Uppsala, Sweden [EDTA plasma from inclusion, 2–5 days after the acute ACS, and at 1 year were assessed by Proseek Multiplex CVD III , Sweden , 26. The, Sweden . The plaEchocardiography was performed in the cardiac intensive care unit within 72 h and during follow-up at 1 year. The prospectively collected echo data were retrospectively reviewed by experienced echocardiographers. Two-dimensional echocardiography was performed in the standard apical four-, three-, and two-chamber views. EF was assessed using the biplane Simpson’s method. Cut-off values concerning systolic function were based on current echocardiographic recommendations; normal LVEF ≥ 54% in women and ≥ 52% in men . ExternaBaseline characteristics were presented as median and range for continuous variables, and frequency and percentage for categorical values. A total of 92 biomarkers (CVD III panel) were included in the statistical analyses. The very few missing values (90 for elafin and cathepsin D) were filled by single imputation using chained equations, with age, sex, and all biomarkers as predictors . LVEF anDue to a large number of biomarkers, we used various statistical models. For the univariate analyses, considering differences in one biomarker at a time, biomarkers were tested for univariate association with LVEF and GLS using Mann–Whitney tests, correcting for multiplicity using permutation methods .In the prediction models of LVEF and GLS, we used all biomarkers simultaneously. Taking into consideration that there are few patients for the number of predictors, standard regression methods are likely to lead to severe overfitting. Instead, we used random forest . This alIn total 420 patients had available results from the proteomic profiling. The baseline characteristics of these patients are described in Table Results for LVEF were available in 365 (86.9%) of the patients at inclusion and in 341 (81.2%) 1 year after the ACS. GLS was calculated in 287 out of 365 with results of LVEF (78.6%) at inclusion and 1 year (84.2%). At inclusion, LVEF was in median (min–max) 55 (16–81) % and GLS was − 15.1 (− 24.7– − 4.7) % (Table p < 0.0001 for both). In the permutation tests, several biomarkers were identified as associated with LVEF, but only a minor proportion with GLS  ) and NT-proBNP ) were the biomarkers with the highest association to worse GLSBelow is the link to the electronic supplementary material.


Heart failure syndrome is the final presentation of a series of cardiac diseases. According to the Department of Informatics of the Brazilian National Health System (DATASUS), cardiovascular diseases are the third largest cause of hospitalizations in Brazil and heart failure is the main cause of cardiovascular hospital admissions in this country.Despite all the advances in treatments for heart failure, a significant proportion of such patients evolve to states of refractoriness to clinical treatment. In these situations, it becomes necessary to use advanced procedures such as heart transplantation and long-term mechanical assisted circulation devices.1 However, a large proportion of such patients cannot benefit from this procedure either because of contraindications or because of lack of availability of organs.Heart transplantation is still the gold-standard treatment for refractory heart failure and the mean survival after this procedure is 11 years.2In the light of this scenario, there has been great pressure to develop therapies that provide an alternative to transplantation. This has culminated in the introduction of long-term mechanical assisted circulation devices.The beginnings of the development of mechanical assisted circulation devices date back to 1950, when an extracorporeal circulation machine was first used. In 1964, the National Heart and Lung Institute of the United States created an artificial heart program. Twenty years later, in the 1980s, tests on the HeartMate XVE implant began.3 and was shown to provide a reduction of 48% in the risk of death over a one-year period. However, use of this device presented a high rate of complications such as thromboembolic events and hemolysis.HeartMate XVE was the first generation of long-term mechanical assisted circulation devices. It propelled the blood flow by means of a pulsatile pump that attempted to mimic the flow in the left ventricle. This device was tested in the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial4In 2007, a study comparing HeartMate XVE and HeartMate II, a second-generation device, was published. This new device had a different mechanism, consisting of continuous axial flow. Its technology brought in the advantage of being a smaller device that could be used by individuals of lesser build, with the expectation that it would be possible to use it for a long period, given that it only had a single moving part, its rotor.7Subsequently, axial flow devices dominated in the field of long-term mechanical assisted circulation, for a long period. Centrifugal flow devices then emerged, which brought in the advantages of miniaturization, intrapericardial placement and a bearing-free rotor, achieved through the technologies of electromagnetic or hydrodynamic levitation. These devices reduced hemolysis and adverse events relating to hemocompatibility.8The latest report from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that 77.7% of the long-term devices used in 2019 made use of magnetic levitation, thus showing the growth in this technology over recent years.9Implantation of long-term mechanical assisted circulation devices can be indicated through the following strategies: 1 – As a bridge to candidacy: in situations of clinical conditions that prohibit heart transplantation but which if modifiable would allow the patient to become a candidate for transplantation ; 2 – As a bridge to transplantation: in situations in which the device might provide hemodynamic support and clinical stability until the heart transplantation is performed, within a context of progressively increasing severity of the patient's condition and unavailability of an organ for transplantation within the short term; 3 – As destination therapy: in situations in which the device might provide hemodynamic support and clinical stability for a patient with refractory heart failure who presents contraindications for heart transplantation, thus enabling greater survival and better quality of life, in comparison with clinical treatment using medications.10 given their high cost and the potential growth in the number of heart transplantations that has occurred over recent decades.11 These factors have left Brazil well behind with regard current treatments for advanced heart failure.In Brazil, experience with these devices remains sparse,8Within the worldwide scenario, what we see is that improvements in the technology of long-term mechanical assisted circulation devices and in the expertise of medical teams have consequentially increased the survival of such patients. This has given rise to changes in the range of options for treating refractory heart failure. Long-term mechanical assisted circulation devices are increasing gaining space: not only at the transplantation point but also, especially, as destination therapy, which accounted for more than 70% of the indications in 2019.


Newborns with untreated single ventricles develop pulmonary vascular diseases early in their lives. At that age, during the first eight weeks after birth, clinicians perform pulmonary artery (PA) banding to reduce the blood flow to the lung, decreasing the likelihood of future high vascular resistance or pressure. PA banding is also considered an initial stage in the process of single ventricle palliation procedures. We report a case of a 16-month-old toddler (7 kg) with room air saturation of 82%, diagnosed with tricuspid valve atresia, large atrial and ventricular septal defect, and hypoplastic right ventricle with severe pulmonary arterial hypertension. The baby underwent a successful surgical procedure of PA banding and was discharged after 13 days of hospital stay with a room air saturation of 89%. This case highlighted the benefit of PA banding beyond the stipulated period. In 1952, Muller and Dammann introduced pulmonary artery (PA) banding as a palliative surgical procedure for patients with congenital heart abnormalities that involve a left-right shunt [high pulmonary blood flow (PBF). The procedure aims to prevent irreversible changes in the pulmonary vascular bed while the patient is awaiting definitive surgery to correct the congenital cardiac defect . PA banding is used for a few types of ventricular septal defects and SVs. Moreover, it is usually done within the first eight weeks after birth, while it is not recommended after 12 weeks . Our stuThe Institutional Ethics Committee (IEC-2) at H.M. Patel Centre for Medical Care and Education, Anand, Gujarat  approved this study. The patient's parents gave their consent to use the medical data of their child.Presentation2) of 82 % in the four limbs. The patient was born at term after a low-segment Caesarean section with a birth weight of 3.1 kg. and cried immediately after birth (CIAB). On chest X-ray, we notice an increase in pulmonary vascularity besides clear cardiomegaly  presented to our pediatric cardiac outpatient clinic with respiratory distress, cyanosis, and room air saturation , large atrial septal defect (ASD) with right-left shunt, large ventricular septal defect (VSD) with left-right shunt, hypoplastic right ventricle, dominant left ventricle, and severe pulmonary arterial hypertension. Before the PA banding procedure, the toddler underwent complete preoperative clinical examinations, including a cardiac and neurological examination. Besides routine laboratory investigations, qualitative molecular analyses were negative for SARS-CoV2 (COVID-19)  was used for banding. The width was 3-5 mm, while the thickness equaled 0.6 mm. Subsequently, the band was placed without distorting the nearby PA branches. However, we fixed it with a 5/0 or 6/0 polypropylene suture to the adventitia of the main PA. There was minimal blood loss, and the whole procedure took up to two hours Figure .Formula Employed for Band CircumferenceThe initial assessment of the band diameter was conducted as Trusler (1972) previously described. Accordingly, the diameter for infants with simple defects without intra-cardiac bi-directional mixing disorders is (20 mm + 1 mm)/kg. At the same time, it is (24 mm + 1 mm)/kg in the presence of bi-directional mixing disorders.2= 80% when FiO2 is nearly equal to 21%. Any new onset arrhythmia was considered a non-tolerance for the band. Echocardiography was performed to measure the supravalvar diameter and pulmonary valve diameter during the surgery; the accepted reduction in supravalvar diameter was approximately 50%  0, the baby had low cardiac output with a drop in urine output and a rise in potassium levels. To improve her renal function, peritoneal dialysis was initiated on POD 0 and continued till POD 5 (Day 5 after surgery) when the child was extubated (after 122 hours of ventilatory time). It was discontinued as the edema settled and renal function improved. No pulmonary edema was noted. The patient was gradually introduced to a liquid diet and then full meals; finally, she was discharged in stable condition. At the time of discharge, her SpOPulmonary artery band gradient = ABP-PAP (both systolic) = 95−37=58 mm Hg. The PA band was fixed at 26.5 cm circumference approximately on the Goretex/ polytetrafluoroethylene (PTFE) strip Figures , 5SV with pulmonary stenosis is usually diagnosed early due to its unique signs. Conversely, SV with high blood flow in the pulmonary vascular bed lacks clinical manifestations such as clear cyanosis and harsh murmur, making the diagnosis difficult. Therefore, early diagnosis is essential for SV patients with unrestricted PBF as the suitable age for surgical repair is four to eight weeks; however, some experts consider 12 weeks suitable as well . Though,However, nearly 75% of patients with SV do not survive within the first three years of their life . In the Early mortality causes include recurrent respiratory infections, refractory heart failure, and severe growth failure. However, even if some patients survive beyond three years, they usually develop early-onset pulmonary vascular disease (PVD) much quicker than the standard left-to-right shunts. Furthermore, these complex defects have a poor survival rate of nearly two decades compared to standard Eisenmenger patients .Through this case, we tried to determine whether late PA banding can halt the disease progression for the patient to become eligible for BDG . In the case we reported, a clinical improvement was observed during the postoperative follow-up period (three months), including weight gain and fewer respiratory tract infection episodes. Persistent weight gain is an essential parameter that reflects infant well-being.SV defect may come with another defect, such as cor triatriatum and supramitral ring, in addition to mitral valve stenosis, that may obstruct pulmonary venous return, leading to pulmonary venous hypertension (PVH), which worsens the situation of children above one years old. PVH also participates in the pathology of pulmonary arterial hypertension (PAH) passively by elevating pulmonary venous pressures and actively by causing pulmonary arteriolar vasoconstriction ,16. Our Previous studies have investigated PA banding outcomes in SV patients. However, Sasikumar et al. are the only ones who examined the outcome of late PA banding. He enrolled 32 patients above eight years . The cut2 above 85% in room air and proved high PBF , which is irrespective of the presentation age. PA band may hinder PVD progression and reduce the number of eligible patients for SV palliation. Patients who adhere to the Fontan pathway unequivocally show better long-term outcomes than those who do not.The current consensus defines the criteria for patients who deserve a chance of PA banding, even at a late age, within the first six months of life. That includes SpOManaging SV with unrestrictive PBF is challenging for infants in the developing world. Even when performed beyond the stipulated period, the PA band might improve patients' quality of life. Patients who undergo late PA bands may also progress to SV palliation and get better outcomes even if they do not fit into such a category. Surgeons should always keep in mind the risk-benefit ratio before going forward with this procedure. However, definite conclusions cannot be drawn at this point in time until more research data is available in this subset.