Depressed Left Ventricular Function Research Articles

Complementary use of conduction system pacing techniques for the “pace and ablate” strategy in permanent atrial fibrillation - a case report

Abstract Introduction The feasibility of the conduction system pacing combined with atrioventricular node ablation was demonstrated in patients with atrial fibrillation in whom rate control can’t be achieved with medication and heart failure. Clinical case We present a case of an 82-year-old man with a personal history of permanent atrial fibrillation, admitted with symptoms of heart failure. The resting electrocardiogram showed a very fast ventricular response, and the echocardiography showed a depressed left ventricular function, raising the suspicion of a tachycardia-mediated cardiomyopathy. Since the patient was on maximum doses of atrioventricular nodal-blocking drugs, we opted for a physiological pacing and atrioventricular node ablation strategy. First, the His bundle capture was achieved at low pacing thresholds, and ablation of the atrioventricular node was attempted. Unfortunately, after several failed attempts, an acute increase in the His bundle capture threshold was noted, suggesting inadvertent tissue ablation beneath the pacing lead. In this scenario, we removed the lead from the His bundle area and achieved optimal left bundle branch area pacing. With the lead in this position, atrioventricular node ablation was performed during the first attempt. At the six-month follow-up, there was no recovery of atrioventricular node conduction. Device interrogation revealed stable pacing and sensing parameters, and there was a significant improvement in clinical status and left ventricular function. Conclusions Mastering both His bundle pacing and left bundle branch area pacing offers the potential to overcome intraprocedural challenges, giving alternative strategies to achieve physiological pacing. These approaches can be used interchangeably based on the evolving dynamics of the procedure and the patient’s specific needs.

Clinical significance and prognostic value of right bundle branch block in permanent pacemaker patients.

In patients undergoing pacemaker implantation with no prior history of heart failure (HF), the presence of left bundle branch block (LBBB) has been identified as an independent predictor of HF-related death or hospitalization, while the prognostic significance of right bundle branch block (RBBB) remains uncertain. We aimed to assess the long-term risk of all-cause mortality in patients with a standard indication for permanent pacing and normal or moderately depressed left ventricular function when RBBB is detected at the time of implantation. We retrospectively enrolled 1348 consecutive patients who had undergone single- or dual-chamber pacemaker implantation at the study center, from January 1990 to December 2022. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded. The baseline 12-lead electrocardiogram revealed an RBBB in 241 (18%) and an LBBB in 98 (7%) patients. During a median follow-up of 65 [25th-75th percentile: 32-117] months, 704 (52%) patients died. The combined endpoint of cardiovascular death or HF hospitalization was reached by 173 (13%) patients. On multivariate analysis, RBBB was confirmed as an independent predictor of death [hazard ratio, 1.33; 95% confidence interval (CI), 1.09-1.63; P = 0.005]. However, when considering the combined endpoint of cardiovascular death and HF hospitalization, this endpoint was independently associated with LBBB (hazard ratio, 2.13; 95% CI, 1.38-3.29; P < 0.001), but not with RBBB. In patients with standard pacemaker indications and normal or moderately depressed left ventricular function, the presence of basal RBBB was an independent predictor of mortality. However, it was not associated with the combined endpoint of cardiovascular death and HF hospitalization.

Clinical significance and prognostic value of right bundle branch block in permanent pacemaker patients

Abstract Aim In patients undergoing pacemaker implantation with no prior history of heart failure (HF), the presence of left bundle branch block (LBBB) has been identified as an independent predictor of HF-related death or hospitalization, while the prognostic significance of right bundle branch block (RBBB) remains uncertain. We aimed to assess the long-term risk of all-cause mortality in patients with a standard indication for permanent pacing and normal or moderately depressed left ventricular function when RBBB is detected at the time of implantation. Methods We retrospectively enrolled 1348 consecutive patients who had undergone single- or dual-chamber pacemaker implantation at the study center, from January 1990 to December 2022. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded. Results The baseline 12-lead electrocardiogram revealed an RBBB in 241 (18%) and an LBBB in 98 (7%) patients. During a median follow-up of 65 [25th-75th percentile: 32-117] months, 704 (52%) patients died. The combined endpoint of cardiovascular death or HF hospitalization was reached by 173 (13%) patients. On multivariate analysis, RBBB was confirmed as independent predictor of death (Hazard Ratio, 1.33; 95% CI, 1.09–1.63; P=0.005). However, when considering the combined endpoint of cardiovascular death and HF hospitalization, this endpoint was independently associated with LBBB (Hazard Ratio, 2.13; 95% CI, 1.38–3.29; P&amp;lt;0.001), but not with RBBB. Conclusions In patients with standard pacemaker indications and normal or moderately depressed LV function the presence of basal RBBB was an independent predictor of mortality. However, it was not associated with the combined endpoint of cardiovascular death and HF hospitalization.Time to event

Implications and hidden toxicity of cardiometabolic syndrome and early-stage heart failure in carfilzomib-induced cardiotoxicity.

Cancer therapy-related cardiovascular adverse events (CAEs) in presence of comorbidities, are in the spotlight of the cardio-oncology guidelines. Carfilzomib (Cfz), indicated for relapsed/refractory multiple myeloma (MM), presents with serious CAEs. MM is often accompanied with co-existing comorbidities. However, Cfz use in MM patients with cardiometabolic syndrome (CMS) or in heart failure with reduced ejection fraction (HFrEF), is questionable. ApoE-/- and C57BL6/J male mice received 14 weeks Western Diet (WD) (CMS models). C57BL6/J male mice underwent permanent LAD ligation for 14 days (early-stage HFrEF model). CMS- and HFrEF-burdened mice received Cfz for two consecutive or six alternate days. Daily metformin and atorvastatin administrations were performed additionally to Cfz, as prophylactic interventions. Mice underwent echocardiography, while proteasome activity, biochemical and molecular analyses were conducted. CMS did not exacerbate Cfz left ventricular (LV) dysfunction, whereas Cfz led to metabolic complications in both CMS models. Cfz induced autophagy and Ca2+ homeostasis dysregulation, whereas metformin and atorvastatin prevented Cfz-mediated LV dysfunction and molecular deficits in the CMS-burdened myocardium. Early-stage HFrEF led to depressed LV function and increased protein phosphatase 2A (PP2A) activity. Cfz further increased myocardial PP2A activity, inflammation and Ca2+-cycling dysregulation. Metformin co-administration exerted an anti-inflammatory potential on the myocardium without improving LV function. CMS and HFrEF seem to exacerbate Cfz-induced CAEs, by presenting metabolism-related hidden toxicity and PP2A-related cardiac inflammation, respectively. Metformin retains its prophylactic potential in the presence of CMS, while mitigating inflammation and Ca2+ signalling dysregulation in the HFrEF myocardium.

Diastolic function assessment with four-dimensional flow cardiovascular magnetic resonance using automatic deep learning E/A ratio analysis

BackgroundDiastolic left ventricular dysfunction is a powerful contributor to the symptoms and prognosis of patients with heart failure. In patients with depressed left ventricular systolic function the EA ratio is the first step to defining the grade of diastolic dysfunction. Doppler echocardiography is the preferred imaging technique for diastolic function assessment, while CMR is less established as a method. Previous 4D Flow-based studies have looked at the EA ratio proximally to the mitral valve, requiring manual interaction. In this study we compare an automated, deep learning-based, and two semiautomated approaches for 4D Flow CMR-based EA ratio assessment to conventional, gold standard echo-based methods. MethodsNinety-seven subjects with chronic ischemic heart disease underwent a cardiac echo followed by an MRI investigation. 4D Flow-based EA ratio values were computed using three different approaches; two semi-automated, assessing the EA ratio by measuring the inflow velocity (MVvel) and the inflow volume (MVflow) at the mitral valve plane, and one fully automated, creating a full LV segmentation using a deep learning-based method within which the EA ratio could be assessed without constraint to the mitral plane (LVvel). ResultsMVvel, MVflow, and LVvel EA ratios were strongly associated with Echo EA ratio (R2= 0.60, 0.58, 0.72). LVvel peak E and A showed moderate association to Echo peak E and A, while MVvel values were weakly associated. MVvel and MVflow EA ratios were very strongly associated with LVvel (R2= 0.84, 0.86). MVvel peak E was moderately associated with LVvel, while peak A showed strong association (R2= 0.26, 0.57). Discussion and ConclusionPeak E, peak A and EA ratio are integral to the assessment of diastolic dysfunction and may expand the utility of CMR studies in patients with cardiovascular disease. While underestimation of absolute peak E and A velocities was noted, the EA ratio measured with all three 4D Flow methods was strongly associated with the gold standard Doppler echocardiography. The automatic, deep learning-based method performed best, with the most favorable runtime of ~40seconds. As both semiautomatic methods associated very strongly to LVvel, they could be employed as an alternative for estimation of EA ratio.

Correlation of ventricular pacing burden and left ventricular function in patients with heart failure with reduced ejection fraction.

Pacemaker-induced cardiomyopathy is a well described phenomenon in patients with preserved ejection fraction at the time of permanent pacemaker implant. One of the identified risk factors for pacemaker-induced cardiomyopathy is the degree of ventricular pacing burden. However, it is unclear how a high right ventricular pacing burden affects patients with depressed left ventricular function at the time of pacemaker implantation. We sought to assess the relationship between right ventricular pacing and change in left ventricular function over time. We conducted an analysis of all patients who had received either a single or dual lead cardiac implantable electronic devices, excluding biventricular devices, and had a prior transthoracic echocardiogram demonstrating an ejection fraction of less than 50%. The primary end-point was the correlation between the percentage of ventricular pacing and the change in LV ejection fraction. Fifty eight patients with preceding heart failure had pacemakers implanted and had follow up echocardiograms. There was no correlation between the degree of ventricular pacing and the absolute change in LV function (r = .04, p = .979). None of the previously identified risk factors for pacemaker induced cardiomyopathy were predictive of a significant fall in ejection fraction. The degree of RV pacing and other established risk factors for pacemaker-induced cardiomyopathy in patients with normal left ventricular function at the time of implantation do not appear to carry the same risk in patients with pre-existing heart failure who receive either single or dual lead pacemakers.

External validation of the Antwerp score: a novel score for predicting responders to catheter ablation of atrial fibrillation in patients with depressed left ventricular function

Abstract Introduction Little exists to identify patients with heart failure (HF) and atrial fibrillation (AF), who will benefit from pulmonary vein isolation (PVI). The Antwerp score was proposed as a new prediction model to identify patients with recovery left ventricular ejection fraction (LVEF) after PVI for AF. Purpose To externally validate the Antwerp score in a large cohort of patients undergoing PVI. Methods Patients with reduced LVEF (&amp;lt; 50%) scheduled to undergo PVI at our hospital were retrospectively analyzed. These were then classified as responders or non-responders to PVI according to the "Universal definition of HF". For each patient, the Antwerp score was calculated, and the performance of the score in predicting LVEF recovery after PVI was evaluated using receiver operating characteristic (ROC) curves and calibration plots. Results Between May 2010 and January 2022, 1665 patients underwent CA for AF at our institution. Of these, 208 patients (median age 63 [IQR 54-69] years, 19% women) had reduced LVEF at presentation and were included in the final analysis (27% with paroxysmal and 73% with persistent AF). The median LVEF at baseline was 43% [IQR 38-46]. At 30 [IQR 20-34] months follow-up after the index procedure, 161 patients (77%) were responders, and 47 patients (23%) were non-responders. The median time to LVEF recovery in responders was 8 [IQR 3-22] months. Between responders and non-responders, differences in AF type were not significant (p = 0.99), while QRS width, absence of known HF etiology and LAVI were significant (p&amp;lt;0.001, p&amp;lt;0.001 and p=0.03). After adjusting for difference in baseline characteristics and procedural outcomes between responders and non-responders, only a QRS duration&amp;lt;120 ms (p=0.002) and absence of known etiology (p&amp;lt;0.001) remained statistically significant with LVEF recovery (Figure). The Antwerp score had an area under the curve (AUC) of 0.75 (95% CI 0.67-0.83). A model containing QRS&amp;lt;120 ms and absence of known etiology performed similarly to the complete Antwerp model (Likelihood Ratio p=0.77). Conclusion The Antwerp score has a moderate ability to identify patients with the recovery of LVEF after PVI in an external population, showing modest rule-in and rule-out capabilities. QRS width and absence of known HF etiology were confirmed as excellent predictors of LVEF recovery.Figure

Incidentally induced atrial fibrillation during programmed electrical stimulation in patients with depressed left ventricular systolic function after an acute myocardial infarction: a CARISMA substudy

Abstract Background The aim of this study was to investigate the clinically significant value of incidentally induced atrial fibrillation (AF) during programmed electrical stimulation (PES) in patients with left ventricular systolic dysfunction (≤40%) after an acute myocardial infarction (MI). Methods In this study we included 231 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study. These patients were identified 3-21 days after being diagnosed with an MI, had left ventricular ejection fraction ≤40% and had no prior history of AF. They all received an implantable cardiac monitor (ICM) and were continuously monitored for cardiac arrhythmias for 2 years. A PES was performed 6 weeks post-MI with pacing from the right atrium and coronary sinus for induction of SVT and from the ventricular apex and outflow tract with up to three extra stimuli for induction of VT. Induction of AF was unwanted but reported if this incidentally occurred. Results AF was induced in 34 patients (15%) during the PES of which 10 (29%) later developed AF. A total of 61 patients (26%) developed AF within 2-years follow-up and the overall risk of AF was not significantly increased in patients with PES induced AF compared to patients without inducible AF (HR 1.6, P=0.14), however, the risk of AF ≤188 days post-MI was slightly increased (HR 3.0, P=0.01). The risk of bradyarrhythmia (HR=0.2, P=0.07), ventricular arrhythmias (HR=0.7, P=0.77) and MACE (HR 0.5, P=0.28) was reduced in patients with inducible AF compared to patients without inducible AF. Conclusions Incidentally induced AF during an electrophysiological study in post-MI patients was relatively frequent (15%) but was not associated with a higher risk of atrial fibrillation, other cardiac brady- or tachy-arrhythmias or major cardiac events. Even though the short-term risk for AF slightly increased, this does not seem to justify anticoagulation treatment or intensified follow-up in these patients.

Abstract 12011: A Case of Emphysematous Pyelonephritis With Use of Empagliflozin

Background: SGLT2i improve cardiovascular (CV) outcome in patients with HFrEF with or without diabetes (DM). Although recent trials and metanalysis have showed improve renal outcomes with SGLT-2i, one should be aware of the potential serious adverse effects with this group of medications including life threatening UTI. Case: 50-year-old female with history of type 2 DM presented with septic shock due to bilateral (B/L) pyelonephritis, with no associated renal calculi. CT of the abdomen also revealed emphysematous pyelonephritis of the left kidney. Few days later, patient went into PEA requiring intubation with return of spontaneous circulation within 4 minutes of advanced cardiac life support. Patient was extubated subsequently later on during her hospitalization. Work up for PEA revealed depressed left ventricular systolic function with an EF of 25-29% with no wall motion abnormality. Patient also developed decompensated HFrEF with development of b/l pleural effusion and generalized anasarca. Cardiology was consulted for management of her cardiomyopathy. She was recommended coronary angiography but she declined. Therefore, Patient was started on guideline direct medical therapy for HF with metoprolol succinate, lisinopril and spironolactone. Due to recent evidence of SGLT-2i improving CV outcomes in patients with HFrEF, it was also recommended to start SGLT-2i. Discussion: On further reviewing regarding use of SGLT-2i and association with UTI, we found a case report causing emphysematous pyelonephritis with use of canagliflozin. Medication reconciliation done at the time of discharge revealed that patient was recently initiated on empagliflozin three months prior to her admission. Therefore, it was speculated that her emphysematous pyelonephritis could be one of the rare complications of SGLT-2i since no other etiologies was noted per urological workup and we decided not to continue SGLT-2i. A search of FAERS from March 2013 through October 2014 identified 19 cases of urosepsis reported with the SGLT2 inhibitors (canagliflozin [n=10] and dapagliflozin [n=9]). All cases resulted in hospitalization. No deaths were reported. Clinicians should be aware of potential life-threatening UTI which may occur with SGLT-2i use.

Effects of Normobaric Hypoxia and Adrenergic Blockade over 72 h on Cardiac Function in Rats.

In rats, acute normobaric hypoxia depressed left ventricular (LV) inotropic function. After 24 h of hypoxic exposure, a slight recovery of LV function occurred. We speculated that prolonged hypoxia (72 h) would induce acclimatization and, hence, recovery of LV function. Moreover, we investigated biomarkers of nitrosative stress and apoptosis as possible causes of hypoxic LV depression. To elucidate the role of hypoxic sympathetic activation, we studied whether adrenergic blockade would further deteriorate the general state of the animals and their cardiac function. Ninety-four rats were exposed over 72 h either to normal room air (N) or to normobaric hypoxia (H). The rodents received infusion (0.1 mL/h) with 0.9% NaCl or with different adrenergic blockers. Despite clear signs of acclimatization to hypoxia, the LV depression continued persistently after 72 h of hypoxia. Immunohistochemical analyses revealed significant increases in markers of nitrosative stress, adenosine triphosphate deficiency and apoptosis in the myocardium, which could provide a possible explanation for the absence of LV function recovery. Adrenergic blockade had a slightly deteriorative effect on the hypoxic LV function compared to the hypoxic group with maintained sympathetic efficacy. These findings show that hypoxic sympathetic activation compensates, at least partially, for the compromised function in hypoxic conditions, therefore emphasizing its importance for hypoxia adaptation.

ANMCO position paper: guide to the appropriate use of the wearable cardioverter defibrillator in clinical practice for patients at high transient risk of sudden cardiac death.

Extended risk stratification and optimal management of patients with a permanently increased risk of sudden cardiac death (SCD) are becoming increasingly important. There are several clinical conditions where the risk of arrhythmic death is present albeit only transient. As an example, patients with depressed left ventricular function have a high risk of SCD that may be only transient if there will be a significant recovery of function. It is important to protect the patients while receiving and titrating to the optimal dose the recommended drugs that may lead to an improved left ventricular function. In several other conditions, a transient risk of SCD can be observed even if the left ventricular function is not compromised. Examples are patients with acute myocarditis, during the diagnostic work-up of some arrhythmic conditions or after extraction of infected catheters while eradicating the associated infection. In all these conditions, it is important to offer a protection to these patients. The wearable cardioverter defibrillator (WCD) is of particular importance as a temporary non-invasive technology for both arrhythmia monitoring and therapy in patients with increased risk of SCD. Previous studies have shown the WCD to be an effective and safe therapy for the prevention of SCD caused by ventricular tachycardia/fibrillation. The aim of this ANMCO position paper is to provide a recommendation for clinical utilization of the WCD in Italy, based upon current data and international guidelines. In this document, we will review the WCD functionality, indications, clinical evidence, and guideline recommendations. Finally, a recommendation for the utilization of the WCD in routine clinical practice will be presented, in order to provide physicians with a practical guidance for SCD risk stratification in patients who may benefit from this device.

ANMCO Position paper: Wearable cardioverter defibrillator appropriate use guidance for the management of patients at high transient risk of sudden cardiac death

Extended risk stratification and optimal management of patients with a permanently increased risk of sudden cardiac death (SCD) is becoming increasingly important. There are several clinical conditions where the risk of arrhythmic death is present albeit only transient. As an example, patients with depressed left ventricular function have a high risk of SCD that may be only transient when there is a significant recovery of function. It is important to protect the patients while receiving the recommended measures and drugs that may either lead or not to an improved left ventricular function. In several other conditions a transient risk of SCD can be observed even if the left ventricular function is not compromised. Examples are patients with acute myocarditis, during the diagnostic work-up of some arrhythmic conditions or after extraction of infected catheters while eradicating the associated infection. In all these conditions it is important to offer a protection to these patients. The wearable cardioverter-defibrillator (WCD) is of particular importance as a temporary non-invasive technology for both arrhythmia monitoring and therapy in patients with increased risk of SCD. Previous studies have shown the WCD to be an effective and safe therapy for the prevention of SCD caused by ventricular tachycardia/fibrillation. The aim of this ANMCO position paper is to provide a recommendation for clinical utilization of the WCD in Italy, based upon current data and international guidelines. In this document we will review the WCD functionality, indications, clinical evidence as well as guideline recommendations. Finally, a recommendation for the utilization of the WCD in routine clinical practice will be presented, in order to provide physicians with a practical guidance for SCD risk stratification in patients who may benefit from this device.

Sudden death in ischemic heart disease: looking for new predictors: polygenic risk.

The phenomenon of sudden death (SD) occurs, in 70% of cases, in people who do not fall within the indications of the guidelines relating to the implantation of the defibrillator. There is a way of inheriting the risk condition by genetic means, the polygenic one, in which mutations are not found, but an increase in alleles of common variations called polymorphisms. The PRE-DETERMINE cohort study has the primary objective of determining whether biological markers, and electrocardiogram can be used to identify individuals more likely to experience SD. Within the study, we investigated the utility of the genome-wide polygenic score for coronary artery disease (GPSCAD) for SD risk stratification in an intermediate-risk population with stable coronary artery disease without severe systolic dysfunction and/or indication for an implantable cardioverter defibrillator in primary prevention. Over a mean follow-up period of 8.0 years, patients in the top decile of GPSCAD were at higher absolute (8.0% vs. 4.8%; P < 0.005) and relative (29% vs. 16%; P < 0.0003) risk of SD compared to the rest of the cohort. No association was found between the highest decile of GPSCAD and other forms of death, cardiac, and non-cardiac. The data on the increase in absolute and relative terms of SD can be used, at this stage, only for a theoretical estimate on the possible efficacy of the defibrillator in the population with chronic coronary artery disease and moderately depressed left ventricular function as number needed to treat and possible reduction of mortality in high-risk patients (those included in the top decile of GPSCAD).

Successful treatment of acute myocardial injury of Duchenne muscular dystrophy with steroids: a case report

BackgroundDuchenne muscular dystrophy (DMD) is an X-linked muscular disease which is caused by the absence of dystrophin. Troponin elevation with acute chest pain may indicate acute myocardial injury in these patients. We report a case of DMD that presented with ACP and troponin elevation, who was diagnosed with acute myocardial injury, and successfully treated with corticosteroids.Case presentationA 9-year-old with DMD was admitted to the emergency department with the complaint of acute chest pain. His electrocardiogram (ECG) revealed inferior ST elevation and serum troponin T was elevated. The transthoracic echocardiography (TTE) demonstrated inferolateral and anterolateral hypokinesia with depressed left ventricular function. An ECG-gated coronary computed tomography angiography ruled out acute coronary syndrome. Cardiac magnetic resonance imaging revealed mid-wall to sub-epicardial late gadolinium enhancement at the basal to the mid inferior lateral wall of the left ventricle and corresponding hyperintensity on T2-weighted imaging, consistent with acute myocarditis. A diagnosis of acute myocardial injury associated with DMD was made. He was treated with anticongestive therapy and 2 mg/kg/day of oral methylprednisolone. Chest pain resolved the next day, and ST-segment elevation returned to normal on the third day. Troponin T decreased in the sixth hour of oral methylprednisolone treatment. TTE on the fifth day revealed improved left ventricular function.ConclusionDespite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with DMD. Acute chest pain attacks with elevated troponin in patients with DMD without coronary artery disease may indicate acute myocardial injury. Recognition and appropriate treatment of acute myocardial injury episodes in DMD patients may delay the development of cardiomyopathy.

Outcomes in neonatal critical and non-critical aortic stenosis: a retrospective cohort study

ObjectiveTo compare long-term survival, reinterventions and risk factors using strict definitions of neonatal critical and non-critical valvular aortic stenosis (VAS).DesignA nationwide retrospective study using data from patient files, echocardiograms and...

634: GLOBAL LONGITUDINAL STRAIN IS ASSOCIATED WITH MORTALITY AFTER PEDIATRIC CARDIAC ARREST

Introduction: Depressed left ventricular function is associated with mortality after pediatric cardiac arrest (CA). Echocardiographic global longitudinal strain (GLS) is more sensitive for poor outcomes than ejection fraction (EF) and shortening fraction (SF), with few studies in children. We aimed to identify the frequency of impaired GLS after pediatric CA and its association with hospital mortality. We hypothesized abnormal GLS is associated with mortality. Methods: This is a retrospective single-center cohort study of children < 18 years of age treated in the pediatric intensive care unit after in- and out-of-hospital CA, with echocardiogram performed within 24 hours of admission between 2013-2020. Patients with congenital heart disease, extracorporeal support, or inability to measure GLS were excluded. EF and SF measurements were abstracted and GLS measured post hoc by an investigator blinded to outcome. Abnormal left ventricular GLS was defined as >-18%. Correlation between GLS, EF and SF were calculated with Spearman’s rho. Logistic regression tested association of GLS with mortality. Area under the receiver operator characteristic (AUROC) curve was calculated for discriminative utility of GLS, EF, and SF with mortality. Results: GLS was measured in 124 subjects and abnormal in 49 (40%). Subjects with abnormal GLS were older (median 8 vs 2 years, p< 0.001), had more ventricular tachycardia/fibrillation as initial rhythm (18% vs 4%, p=0.008) and higher maximum troponin in 24 hours (median 2.6 ng/mL vs 0.5, p=0.002). There was no difference between arrest location or CPR duration based on GLS. Subjects with abnormal GLS had lower median EF (43% vs 63%) and SF (24% vs 37%), with strong inverse correlation between GLS and EF (rho -0.76) and SF (rho -0.71), all p< 0.001. Abnormal GLS had higher mortality (57% vs 33%, p=0.009) and GLS was associated with mortality when controlling for age and initial rhythm [aOR 1.17 per 1% increase in GLS (95% CI 1.09-1.26), p< 0.001]. GLS (AUROC 0.69), EF (0.71) and SF (0.71) had similar discrimination for mortality. Conclusions: Post-arrest GLS is a novel complementary metric, strongly correlated with EF and SF and associated with mortality. Future prospective studies should investigate the prognostic utility of GLS alongside SF and EF.

Outcome of Patients with Left Main Coronary Artery Disease Together with Left Ventricular Dysfunction Following OPCAB and Conventional CABG Surgery

In-hospital mortality and morbidities are significantly higher in patients who undergo coronary artery bypass graft (CABG) surgery having a depressed left ventricular function or a left main (LM) coronary artery disease. Due to the improvement in technique and clinical outcome, Off-pump Coronary Artery Bypass (OPCAB) is thought to be beneficial in patients with depressed left ventricular function by avoiding prolonged ischemic time. This study was performed with an aim to assess whether OPCAB is better than conventional on-pump CABG (CCAB) in these sub-groups of patients. We purposively selected 100 patients with left main coronary artery disease (defined as ≥50% stenosis) with reduced left ventricular ejection fraction (defined as ejection fraction 40% or less) who underwent elective CABG in National Institute of Cardiovascular Diseases (NICVD) between January 2014 and December 2020. Among them OPCAB was done in 50 patients and conventional CABG in another 50 patients. Both groups had similar pre-operative parameters. Total operative time, intubation time, blood loss, requirement for blood and blood products, intensive care unit (ICU) stay and hospital stay were all significantly lower in the OPCAB group. Post-operative complications were not statistically different among the two groups. Study finds that patients with left main coronary artery disease with left ventricular dysfunction can be safely revascularized in OPCAB technique.&#x0D; Bangladesh Med J. 2021 Sept; 50(3): 14-19

Cardiovascular disease and chimeric antigen receptor cellular therapy.

Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary personalized therapy that has significantly impacted the treatment of patients with hematologic malignancies refractory to other therapies. Cytokine release syndrome (CRS) is a major side effect of CAR T therapy that can occur in 70–90% of patients, with roughly 40% of patients at grade 2 or higher. CRS can cause an intense inflammatory state leading to cardiovascular complications, including troponin elevation, arrhythmias, hemodynamic instability, and depressed left ventricular systolic function. There are currently no standardized guidelines for the management of cardiovascular complications due to CAR T therapy, but systematic practice patterns are emerging. In this review, we contextualize the history and indications of CAR T cell therapy, side effects related to this treatment, strategies to optimize the cardiovascular health prior to CAR T and the management of cardiovascular complications related to CRS. We analyze the existing data and discuss potential future approaches.

Direct proteomic and high-resolution microscopy biopsy analysis identifies distinct ventricular fates in severe aortic stenosis

The incidence of aortic valve stenosis (AS), the most common reason for aortic valve replacement (AVR), increases with population ageing. While untreated AS is associated with high mortality, different hemodynamic subtypes range from normal left-ventricular function to severe heart failure. However, the molecular nature underlying four different AS subclasses, suggesting vastly different myocardial fates, is unknown. Here, we used direct proteomic analysis of small left-ventricular biopsies to identify unique protein expression profiles and subtype-specific AS mechanisms. Left-ventricular endomyocardial biopsies were harvested from patients during transcatheter AVR, and inclusion criteria were based on echocardiographic diagnosis of severe AS and guideline-defined AS-subtype classification: 1) normal ejection fraction (EF)/high-gradient; 2) low EF/high-gradient; 3) low EF/low-gradient; and 4) paradoxical low-flow/low-gradient AS. Samples from non-failing donor hearts served as control. We analyzed 25 individual left-ventricular biopsies by data-independent acquisition mass spectrometry (DIA-MS), and 26 biopsies by histomorphology and cardiomyocytes by STimulated Emission Depletion (STED) superresolution microscopy. Notably, DIA-MS reliably detected 2273 proteins throughout each individual left-ventricular biopsy, of which 160 proteins showed significant abundance changes between AS-subtype and non-failing samples including the cardiac ryanodine receptor (RyR2). Hierarchical clustering segregated unique proteotypes that identified three hemodynamic AS-subtypes. Additionally, distinct proteotypes were linked with AS-subtype specific differences in cardiomyocyte hypertrophy. Furthermore, superresolution microscopy of immunolabeled biopsy sections showed subcellular RyR2-cluster fragmentation and disruption of the functionally important association with transverse tubules, which occurred specifically in patients with systolic dysfunction and may hence contribute to depressed left-ventricular function in AS.

Aortic Valve Repair in Neonates With Aortic Stenosis and Reduced Left Ventricular Function

This study assessed outcomes of neonatal aortic valve (AoV) repair in presumed high-risk patients with depressed left ventricular (LV) function. A retrospective analysis of all neonates who underwent isolated AoV repair for severe aortic stenosis (AS) was performed. Patients with moderate or severe LV dysfunction were compared to those with normal or mild LV dysfunction. From 1980-2021, 43 neonates underwent isolated AoV repair for AS. Of these, 16 patients (37.2%) had ≥moderate LV dysfunction. Mean LV ejection fraction (EF) was 32.8 ± 9.1%. Valve morphology was mostly unicuspid (68.75%, 11/16). Median age at surgery was 6.5 days (IQR 1-17.5). An optimal repair result with ≤mild AS or aortic regurgitation was achieved in 75% (12/16). There was no early death. One patient (6.25%) required postoperative extracorporeal membrane oxygenation (ECMO) support for 3 days. LVEF improved after surgery to 56.4 ± 12.6% before discharge (P < 0.0001) and normalized in 87.5% (14/16) with a median time of 6.4 days (IQR 3.4-39). Freedom from AoV reoperation was 45.1% (95%CI 17.9-69.3%) and 27.1% (95%CI 6.8-53%) at 5 and 10 years, respectively. Freedom from AoV replacement was 59% (95%CI 27-80.8%) and 31.4% (95%CI 6-62.2%) at 5 and 10 years, respectively. While survival was similar, freedom from AoV reoperation and replacement tended to be lower compared to neonates with preserved LVEF. AoV repair was associated with a low incidence of postoperative ECMO and mortality. LV function normalized after relief of obstruction in most patients before discharge. Late reoperation remained common for those with severely dysplastic valves.