Impaired Left Ventricular Ejection Fraction Research Articles

P73 ANGIOGRAPHY–DERIVED INDEX OF MICROVASCULAR RESISTANCE (IMR–ANGIO) IN TAKOTSUBO SYNDROME

Abstract Introduction Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an “adrenergic storm” upon a susceptible microvascular circulation. The aim of our manuscript was to assess and quantify CMD in patients with TTS through non–invasive angio–derived index of microcirculation (IMRangio) and evaluate its correlation with clinical and instrumental presentation. Methods 41 consecutive TTS patients were retrospectively analyzed. Three different formulas for compute Non–Hyperemic IMRangio (NH–IMRangio) derived by 3D–Quantitative Coronary Angiography (3D–QCA) and Quantitative Flow Reserve (QFR) analysis were used according to each fluidodynamic mathematical expression as reported by respective authors. CMD was defined as an IMRangio ≥ 25. The correlation between NH–IMRangio and clinical presentation and the comparation between the three formulas were provided. Results Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. NH–IMRangio was higher in Left Anterior Descending artery (LAD) than Circumflex artery (CX) and Right Coronary artery (RCA) with either NH–IMRangio 1 (52.7 vs 35.3 vs 41.4), NH–IMRangio 2 (47.2 vs 31.8 vs 37.3) or NH–IMRangio 3 (52.7 vs 36.1 vs 41.8). All patients presented CMD with NH–IMR angio ≥ 25 in at least one territory with each formula. NH–IMRangio in LAD territory was significantly higher in patients presenting with LVEF impairment (≤40%) than in those with preserved ventricular global function (NH–IMRangio LAD 1: 59.3 vs 46.3, p. value=0.030; NH–IMRangio LAD 2: 52.9 vs 41.4, p–value=0.037; NH–IMRangio LAD 3: 59.2 vs 46.3, p–value=0–035). Association between NH–IMRangio computed in LAD and LVEF showed a moderate correlation (NH–IMRangio 1: r = –0,3485, Rho = 0,1214, p = 0,0256; NH–IMRangio 2: r = –0,3513; Rho = 0,1234, p = 0,0256; NH–IMRangio 3: r = –0,3326, Rho = 0,1106, p = 0,0336). Finally, Bland–Altman plot analysis showed good agreement between NH–IMRangio 1 and 3, while NH–IMRangio 2 showed a consistent bias of –5 units against both NH–IMRangio 1 and NH–IMRangio 2 with increasing difference at higher absolute values. Conclusion CMD, assessed with NH–IMRangio, is a common finding in TTS and it is inversely correlate with LVEF dysfunction. The available formulas for NH–IMRangio computation have a substantial superimposable diagnostic performance in assessing CMD.

Long-term follow-up of incident acute coronary syndrome: results from the French MONICA registries over the 2009-2017 period

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Santé Publique France, U1167 - RID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France. Background The prognosis of an acute coronary syndrome (ACS) is strongly affected by the clinical, biological, and angiographic features of the event. However, few studies have characterized long-term recurrences of ACS after an incident (first) event. Aim The goals of this study were (i) to estimate the long-term (9 years) risk of ACS recurrence, including fatal ACS recurrence, among survivors of a first-ever ACS, according to its diagnosis subtype (STEMI / NSTEMI / Unstable angina (UA)) and (ii) to identify factors associated with these risks. Methods We assessed all men and women (aged 35-74) hospitalized between January 2009 and December 2016 for an incident (first-ever) ACS, in the 3 distinct geographical areas covered by the MONICA registries in the north, east and south-west of France, and still alive at discharge (Index event). ACSs were classified as STEMI, NSTEMI and UA. Patients were followed-up until December 2017. Recurrent events were defined as the first non-fatal or fatal ACS occurring after hospital discharge from the index event. Multivariate Cox regression models were used to assess the relationships between recurrent ACS and variables of interest. Results A total of 15,739 incident ACSs were included. The study comprised a total of 63,777 patients-years and a median duration of follow-up of 3.8 [1.6-6.0] years. There were 1,963 (12,4%) recurrent ACSs of which almost half (1,046; 53%) occurred during the first year. The 1-, 5- and 9- year cumulative probabilities of recurrent ACS were 6.7% [6.3-7.1%], 13.4% [12.8-14.0%] and 18.4% [17.4-19.5%], respectively, and those of fatal recurrent ACS were 1.4% [1.2-1.5%], 2.7% [2.3-3.0%] and 4.3% [3.6-4.9%], respectively. Annual 1-year recurrence rates decreased between 2009 and 2016, from 7.4% to 4.0% (p Cochran-Armitage test <0.001). After an index STEMI and NSTEMI, the most frequent form of recurrent event was a NSTEMI, whereas UA was more likely event after an index UA. The age at the time of the event, the geographical region (North to South gradient), the presence of a major event (i.e. resuscitated cardiac arrest, acute pulmonary oedema or cardiogenic shock), and an impaired left ventricular ejection fraction (LVEF) were significantly associated with the risk of recurrence and fatal recurrence. ACS subtype was not associated with recurrent risk after adjustment for confounders. Conclusions In conclusion, after an incident ACS the recurrence rate remained elevated, with one in five patients experiencing a recurrent ACS during a 9-years follow-up. Half of recurrent events occurred within the first year after the index event and NSTEMI was the most frequent form of recurrent event. Age at the time of the event, region, major event and impaired LVEF are factors associated with a higher risk of recurrence, the most important one being an LVEF <35%.

Improving the Characterization of Stage A and B Heart Failure by Adding Global Longitudinal Strain

BackgroundCurrent guidelines distinguish stage B heart failure (SBHF) (asymptomatic left ventricular [LV] dysfunction) from stage A heart failure (SAHF) (asymptomatic with heart failure [HF] risk factors) on the basis of myocardial infarction, LV remodeling (hypertrophy or reduced ejection fraction [EF]) or valvular disease. However, subclinical HF with preserved EF may not be identified with these criteria. ObjectivesThe purpose of this study was to assess the prediction of incident HF with global longitudinal strain (GLS) in patients with SAHF and SBHF. MethodsThe authors analyzed echocardiograms (including GLS) in 447 patients (age 65 ± 11 years; 77% male) enrolled in a prospective study of HF in individuals at risk of incident HF, with normal or mildly impaired EF (≥40%). Long-term follow-up was obtained via data linkage. Analysis was performed using a competing risks model. ResultsAfter a median of 9 years of follow-up, 50 (10%) of the 447 patients had new HF admissions, and 87 (18%) died. In multivariable analysis, all imaging variables were independent predictors of HF admissions, including left ventricular ejection fraction (LVEF) (HR: 0.97 [95% CI: 0.94-0.99]), LV mass index (HR: 1.01 [95% CI: 1.00-1.02]), left atrial volume index (HR: 1.02 [95% CI: 1.00-1.05]), and E/e′ (HR: 1.05 [95% CI: 1.01-1.24]), incremental to clinical variables (age and Charlson comorbidity score). However, the addition of GLS provided value incremental to both clinical and other echocardiographic parameters (P = 0.004). Impaired GLS (<18%) (HR: 4.09 [95% CI: 1.87-8.92]) was independent and incremental to all clinical and other echocardiographic variables in predicting HF, and impaired LVEF, left ventricular hypertrophy, left atrial enlargement, high E/e′, or SBHF were not predictive. ConclusionsThe inclusion of GLS as a criterion for SBHF would add independent and incremental information to standard markers of SBHF for the prediction of subsequent HF admissions.

The Relationship Between Pre-existing Coronary Heart Disease and Cognitive Impairment Is Partly Explained by Reduced Left Ventricular Ejection Fraction in the Subjects Without Clinical Heart Failure: A Cross-Sectional Study.

BackgroundCoronary heart disease (CHD) is closely associated with cognitive impairment, especially in severe cases of heart failure. However, it is unclear whether cardiac systolic function plays a role in the relationship between pre-existing CHD and cognitive impairment in subjects without clinical heart failure.MethodsIn total, 208 subjects from the First Affiliated Hospital of Xi’an Jiaotong University were recruited from June 2014 to January 2015, and were divided into CHD (n = 118) and non-CHD (n = 90) groups according to the inclusion and exclusion criteria. The global cognitive function of all subjects was assessed by the Mini-Mental State Examination (MMSE) and cognitive impairment was defined as the score lower than the cutoff value. Left ventricular ejection fraction (LVEF) was measured using transthoracic echocardiograms. The relationship among pre-existing CHD, LVEF, and cognitive impairment was analyzed by multivariate logistic regression.ResultsIn total, 34 subjects met the criteria of cognitive impairment. Univariate analysis showed that the cognitive impairment prevalence in the CHD group was significantly higher than that in the non-CHD group (22.0 vs. 8.9%, p = 0.011). Multivariate logistic analysis revealed that CHD was significantly associated with a higher risk of cognitive impairment (odds ratio [OR] = 3.284 [95% CI, 1.032–10.450], p = 0.044) after adjusting for confounds except for LVEF. However, the OR of CHD decreased (OR = 2.127 [95% CI, 0.624–7.254], p = 0.228) when LVEF was further corrected as a continuous variable, and LVEF was negatively associated with the risk of cognitive impairment (OR = 0.928 [95% CI, 0.882–0.976], p = 0.004).ConclusionPre-existing CHD is associated with a higher risk of cognitive impairment, and such an association can be considerably explained by reduced LVEF. An impaired cardiac systolic function may play a key role in the relationship between CHD and cognitive impairment among patients with pre-heart failure conditions.

PO-701-06 PREDICTORS OF SUDDEN CARDIAC DEATH AND ARRHYTHMOGENICITY IN PATIENTS WITH MARFAN`S SYNDROME

Marfan´s syndrome caused by FBN1 mutation is associated with sudden cardiac death and ventricular arrhythmias. Data evaluating predictors for these events is scarse. We evaluated predictors of rhythm events and sudden cardiac death in patients with Marfan`s syndrome. In this prospective study 94 adult marfan patients (60 % male, 42 ± 15 years) with FBN1 mutation and a follow up of at least 1 months (median: 5 years, IQR: 3.1 - 10) were included. Baseline serum N-terminal pro-brain natriuretic peptide (NT-proBNP), transthoracic echocardiogram, 12-lead resting ECG and epidemiological parameters were assessed for further analysis and predictor selection. Primary endpoint was composed of ventricular tachycardia, arrhythmogenic syncope or sudden cardiac death. In a mean follow-up time of 6.1 ± 4 years 15 (16 %) marfan patients suffered from rhythm event or sudden cardiac death.Left atrial volume, age, mitral-valve prolaps, impaired left ventricular ejection fraction, NT-proBNP, gender, QRS duration, T-peak-T-end intervals with derivatives and aortic bulbus diameter index were included in further model selection process. We then performed statistical learning methods with best subset selection for model evaluation to identify predictors of composite endpoint. Subsequent multivariate Cox-regression analysis revealed hazard ratios. LA volume (ml) (HR 1.03 per ml, p<0.001), impaired left ventricular ejection fraction (HR: 41.7, p<0.001), male-gender (HR: 4.5, p=0.06), QRS duration (HR: 1.03 per ms, p=0.02) and TpTe maximum (HR: 1.08 per ms, p=0.02) were identified as independent predictors for the combined primary endpoint. NT-proBNP was highly correlated to LA volume and therefore was not significant in the multivariate model. In a statistical learning model combination of echocardiographic and electrocardiographic parameters performed best in prediction power of rhythm events and sudden cardiac death in patients with Marfan´s syndrome.

Incremental Prognostic Value of Left Ventricular Global Longitudinal Strain in Patients with Preserved Ejection Fraction Undergoing Transcatheter Aortic Valve Implantation

Evaluation of left ventricular global longitudinal strain (LVGLS) has allowed better characterization than left ventricular ejection fraction (LVEF) of subtle differences in left ventricular performance. The aim of this study was to determine whether LVGLS has prognostic value in patients with severe aortic stenosis and preserved LVEF undergoing transcatheter aortic valve implantation(TAVI). Among 412 consecutive patients who underwent TAVI, 344 patients (mean age, 78.9±5.0years; 161 men) with preserved LVEF (≥50%) at baseline were analyzed. Patients with low LVEF (<50%) were used as a comparison group in the survival analysis. The primary and secondary end points were all-cause death and a composite of cardiovascular death and heart failure hospitalization, respectively. The mean LVGLS and LVEF were -17.1±2.7% and 63±5%, respectively. Impaired LVGLS was defined as >-16%, which was the first LVGLS quartile (cutoff value, -16%). The estimated actuarial 5-year survival rate was 81.7±4.2% in the normal LVGLS group and 66.8±7.5% in the impaired LVGLS group (P=.005). In the multivariable analysis, impaired LVGLS was an independent predictor of all-cause death (adjusted hazard ratio, 2.26; 95% CI, 1.11-4.60) and the composite outcome (adjusted hazard ratio, 3.03; 95% CI, 1.45-6.33). Moreover, the impaired LVGLS group had a poor prognosis, similar to the impaired LVEF group (<50%). The addition of the absolute value of LVGLS to the clinical parameters and LVEF led to significant improvement in the prediction of all-cause mortality. In patients with severe aortic stenosis and preserved LVEF undergoing TAVI, subclinical LV dysfunction defined by impaired LVGLS is independently associated with poor clinical outcomes. LVGLS measurement provides incremental prognostic value above the established clinical and echocardiographic parameters.

Low mechano-energetic efficiency is associated with future left ventricular systolic dysfunction in hypertensives.

AimsIn a hypertensive population with optimal blood pressure control with a long‐term follow‐up, we aimed at analysing possible predictors of left ventricular (LV) ejection fraction (LVEF) reduction, including indexed mechano‐energetic efficiency (MEEi), a well‐recognized echo‐derived parameter of LV performance.Methods and resultsThe study population included 5673 hypertensive patients from the Campania Salute Network with a long‐term follow‐up, normal baseline LVEF (≥50%), and no prevalent cardiovascular (CV) disease. Patients developing LVEF impairment (LVEF < 50% or a reduction of at least 10 percentage points compared with baseline) were compared with patients with persistently normal LVEF. Optimal blood pressure control was achieved in about 80% of patients. Patients who experienced LVEF reduction were 2.41% during a long‐term follow‐up (mean duration 5.6 ± 3.9 years). At baseline, they were older (59.46 ± 11.58 vs. 53.40 ± 11.41, P < 0.0001) and showed higher LV mass index (53.3 ± 12.83 vs. 47.56 ± 9.58, P < 0.0001), left atrial (LA) volume index (14.4 ± 4.2 vs. 13.1 ± 2.8, P < 0.0001) and carotid intima–media thickness (1.99 ± 0.86 vs. 1.61 ± 0.73, P < 0.0001), lower MEEi (0.32 ± 0.08 vs. 0.34 ± 0.07, P = 0.037), and higher prevalence of CV events during follow‐up (13.9% vs. 3%, P < 0.0001) compared with patients with persistently normal LVEF. A logistic regression analysis, performed after running univariate analyses and selecting parameters significantly associated with LVEF reduction, showed that having a CV event [odds ratio (OR) 7.57, P < 0.0001], being in the lowest MEEi quartile (OR 2.43, P = 0.003), and having a larger LA volume index (OR 1.08, P = 0.028) were all parameters independently associated with the development of LV systolic dysfunction. A further logistic regression model, performed by excluding patients experiencing CV events, demonstrated that the lowest MEEi quartile was independently associated with the evolution towards LVEF reduction (OR 2.35, P = 0.004), despite significant impact of LA volume index (OR 1.08, P = 0.023) and antiplatelet therapy (OR 1.89, P < 0.01). Receiver operating characteristic curves showed that the model including MEEi had higher accuracy than the model without MEEi in predicting LVEF reduction (areas under the curve 0.68 vs. 0.63, P = 0.046).ConclusionsLower values of MEEi at baseline identify hypertensive patients more liable to develop LVEF reduction. In hypertensive setting, MEEi evaluation improves risk stratification for development of LV systolic dysfunction during long‐term follow‐up.

A new prediction model for left ventricular systolic function recovery after catheter ablation of atrial fibrillation in patients with heart failure: The ANTWOORD Study

Backgroundin patients with heart failure (HF) and atrial fibrillation (AF), AF ablation improves left ventricular ejection fraction (LVEF), along with prognosis, in a variable percentage of patients. We aimed to investigate the predictors of LVEF recovery after AF ablation and to develop a prediction model for individualized assessment. Methodswe conducted an observational, retrospective, single-centre study on 111 consecutive patients with AF and HF with impaired LVEF (<50%) undergoing ablation. Patients were divided into Responder vs. Non-Responder according to the “Universal definition of HF”. Clinical predictors were evaluated by multivariate logistic regression analysis and cross-validation technique. Independent predictors were used to build an internally validated prediction model. ResultsResponders (54%) had significantly shorter QRS duration and less dilated left atrium. Persistent AF and absence of a known etiology were more frequent among Responders. AF recurrence was similar between the two groups (p = 0.2), but the percentage of patient with persistent AF after ablation was significantly lower among Responders (p < 0.001). Absence of known etiology, presence of persistent AF, left atrial volume index<50 mL/m2, and QRS < 120 msec were independent predictors of LVEF recovery and composed the Score (AUC 0.93;95%CI 0.88–0.98–p < 0.001). Patients with Score ≤ 1 had 90% likelihood of LVEF recovery, compared to 5% in patients with 3–6. ConclusionsPatients with wide QRS, known HF etiology, dilated left atrium, and paroxysmal AF were less likely to recover LVEF after AF ablation. A new score system based on the above-mentioned parameters adequately predicts LVEF recovery after AF ablation. These results warrant confirmation and prospective validation.

Prediction of Sudden Cardiac Arrest in the General Population: Review of Traditional and Emerging Risk Factors.

Sudden cardiac death (SCD) is the most common and devastating outcome of sudden cardiac arrest (SCA), defined as an abrupt and unexpected cessation of cardiovascular function leading to circulatory collapse. The incidence of SCD is relatively infrequent for individuals in the general population, in the range of 0.03%-0.10% per year. Yet, the absolute number of cases around the world is high because of the sheer size of the population at risk, making SCA/SCD a major global health issue. On the basis of conservative estimates, there are at least 2 million cases of SCA occurring worldwide on a yearly basis. As such, identification of risk factors associated with SCA in the general population is an important objective from a clinical and public health standpoint. This review will provide an in-depth discussion of established and emerging factors predictive of SCA/SCD in the general population beyond coronary artery disease and impaired left ventricular ejection fraction. Contemporary studies on the association of age, sex, race, socioeconomic status, and the emerging contribution of diabetes and obesity to SCD risk beyond their role as atherosclerotic risk factors are reviewed. In addition, the role of biomarkers, particularly electrocardiographic ones, on SCA/SCD risk prediction in the general population are discussed. Finally, the use of machine learning as a tool to facilitate SCA/SCD risk prediction is examined.

Septal versus apical pacing sites in permanent right ventricular pacing: The multicentre prospective SEPTAL-PM study

The optimal right ventricular pacing site for patients requiring pacemaker implantation for permanent atrioventricular block is a matter of debate. Long-term right ventricular apical pacing has been associated with left ventricular ejection fraction impairment and heart failure. Right ventricular septal pacing has been proposed as an alternative. The aim of this randomized prospective multicentre trial was to compare left ventricular remodelling and outcomes between right ventricular apical and septal pacing after mid-term follow-up. Patients requiring pacemaker implantation for high-degree atrioventricular block were enrolled and randomized in a 1:1 fashion to receive a right ventricular apical or septal lead. A total of 141 patients were included, 69 in the septal group and 72 in the apical group. Both groups exhibited similar left ventricular ejection fractions after 18 months of follow-up (septal 57.1±11.9% vs. apical 57.4±13.4%), and left ventricular ejection fraction variation was similar in the two groups at the end of follow-up (septal -1.5±13.2% vs. apical 0.3±13.3%). Additionally, left ventricular volume, quality of life and 6-minute walk distance were similar in the two groups. However, patients in the septal group were more likely to be asymptomatic, with a significantly lower concentration of N-terminal prohormone of brain natriuretic peptide. Lastly, lead position did not impact 18-month survival. Pacing from the right ventricular apex does not have any detrimental effect on left ventricular systolic function compared with septal pacing over an 18-month period.

Pregnancy history and long-term progression of cardiomyopathy in LMNA genotype-positive women

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Precision Health Center for optimized cardiac care (ProCArdio), Oslo, Norway Fripro gene positive, Norwegian Research Council, Oslo, Norway Background Competitive and non-competitive exercises have been reported to be deleterious on prognosis of LMNA genotype-positive patients. Comparable to exercise, pregnancy is a prolonged hemodynamic stress situation. Aims We aimed to assess the association between pregnancy history and long-term progression of cardiomyopathy in women with pathogenic or likely pathogenic variants of LMNA (LMNA+). Methods We retrospectively included consecutive LMNA+ females and recorded pregnancy data. We analyzed repeated echocardiographic examinations, including data on left ventricular (LV) end-diastolic diameter (EDD), LV ejection fraction (EF) and LV global longitudinal strain (GLS). We recorded the occurrence of atrial fibrillation (AF), atrioventricular block, sustained ventricular arrhythmias (VA), and implantation of cardiac electronic devices (ICD/CRT-D). We analysed retrospectively complications during pregnancy and peripartum period. Results We included 89 LMNA+ women (28% probands, age 41 ± 16 years), of which 60 had history of pregnancy. Follow-up duration was 5 [IQR: 3-9] years. We analysed 452 repeated echocardiographic examinations. Women with previous pregnancy and nulliparous had a similar annual deterioration of LV EF (-0.5/year vs -0.3/year, p = 0.37, figure left panel), LV GLS (0.1/year vs 0.0/year, p = 0.35, figure right panel) and LV EDD (0.1/year vs 0.2/year, p = 0.09). Number of pregnancies was not associated with increased long-term risk of AF, atrioventricular block, sustained VA or ICD/CRT-D implantation. Pregnancy history was not associated with worse survival free from death, left ventricular assist device or need for cardiac transplantation. Arrhythmias occurred in 9% of pregnancies. No increase of maternal and fetal complications was observed. Conclusions In our cohort of LMNA+ women, pregnancy was not associated with long-term adverse progression of cardiac dysfunction, worsening in arrhythmic progression or reduced event-free survival. Likewise, LMNA+ women generally tolerated pregnancy well, with a small proportion of patients experiencing arrhythmias. Abstract Figure.

Alternating morphology ventricular tachycardia associated with stable coronary artery disease: A case report

Bidirectional ventricular tachycardia (BVT) is part of the spectrum of polymorphic ventricular tachycardia (VT). This is a case report of a 59-year-old male with stable coronary artery disease and baseline normal left ventricular ejection fraction (LVEF) who was followed for high burden symptomatic monomorphic premature ventricular complexes (PVC). He was admitted for syncope. The ECG showed recurrent non-sustained alternating morphology and double cycle length VT runs associated with deterioration in LVEF but without coronary artery disease progression. The patient had a successful catheter ablation of two distinct left ventricular PVC focus. This is a rare ECG pattern of alternating morphology VT similar to a bidirectional VT.

Catheter ablation of ventricular tachycardia in nonischemic cardiomyopathy with near-normal left ventricular ejection fraction.

Patients with idiopathic nonischemic cardiomyopathy (NICM) and near-normal left ventricular ejection fraction (LVEF) may develop ventricular tachycardia (VT). The purpose of this study was to describe procedural characteristics and outcomes in patients requiring ablation for NICM-related VT with near-normal LVEF compared to impaired LVEF. Over 8 years, 77 consecutive patients with NICM-related VT underwent catheter ablation. Of these patients, 47 had idiopathic NICM (20 near-normal LVEF, 27 impaired LVEF). Procedural characteristics and outcomes were compared. Mean age was 64 ± 12years, mean LVEF was 40% ± 14%, and 75% were male. In the near-normal LVEF group compared to the impaired LVEF group, LVEF was higher (54% ± 5% vs 30 ± 8%; P<.001), scar was predominantly located in the perivalvular left ventricle (LV) and basal septum (15/20 [75%]), was smaller in size [bipolar: 9.7 (6.2-32.4) cm2 vs 30.4 (21.1-37.6) cm2, P=.03; unipolar: 23.3 (6.6-39.9) cm2 vs 57.2 (42.2-74.9) cm2, P = .009], and required smaller areas of ablation [7.0 (5.9-14.2) cm2 vs 11.4 (8.5-16.7) cm2, P = .06]. Both groups experienced comparable procedure times, fluoroscopy doses, ablation times, VT cycle lengths, and acute success rates. After final ablation, VA-free survival was comparable between both groups (65% vs 63%; P=.63) at 12 months. Idiopathic NICM-related VT with near-normal LVEF was associated with discrete areas of arrhythmogenic, predominantly intramural, scar in the perivalvular LV and basal septum. Despite smaller scar, patients required similar ablation amounts and experienced comparable long-term outcomes compared to patients with idiopathic NICM-related VT and impaired LVEF. These findings underscore the "three-dimensionality" of substrate, whereby the intramural basal septum forms the third dimension and impacts ablation outcomes.

Beta blokatori su heterogena klasa - farmakološki kriterijumi za izbor

Beta blockers (BB) are one of the essential and irreplaceable parts of modern cardiovascular pharmacotherapy. For decades, the indications for these drugs have been almost exclusively stated for BB as a class. This is not adequate, if we consider how big the inter-individual differences exist within the BB class. Namely, the differences are sometimes diametrically different, and very important; for example, some BBs reduce the risk of sudden cardiac death and some of them do not; some BB prolong life in heart failure with impaired left ventricular ejection fraction, while for others this has not been proven; stroke and minute volume are reduced by most BB, but not all, etc. The same multi-decade flaw applies to contraindications, which are also listed for the entire BB group, instead of every BB individually. An adequate illustration is COPD, which is contraindication for nonselective BB, but not for highly cardioselective ones, such as nebivolol and bisoprolol. The vasodilating property and cardioselectivity are crucial to obtain fewer side effects, which increases the regularity of taking the therapy, and thus provides a proven benefit in several life-threatening diseases. Therefore, by reducing the number and severity of side effects, vasodilatory and cardioselective BB also reduce the risk of sudden discontinuation of BB (BB rebound phenomenon). It is defined as a worsening of the clinical condition and/or findings within a few hours or days discontinuation of taking BB, to the extent that the situation becomes worse than before starting BB therapy. Hydrophilicity/lipophilicity and duration of effect of BB are also important determinants. There is no, the best BB for all patients, but, based on the criteria mentioned in the paper the optimal one can be chosen for a specific patient at a given time.

Human Induced Pluripotent Stem Cell Modelling for Diabetic Cardiomyopathy and its Susceptibility to SARS-CoV2 myocardial damage

For decades, it has been well known that patients with diabetes mellitus can develop ventricular dysfunction, even in the absence of coronary artery disease. The condition is commonly referred to as diabetic cardiomyopathy and is considered a cardiac muscle disorder due to the metabolic consequences of diabetes mellitus. It is characterized in the early stages by ventricular hypertrophy and diastolic dysfunction, and in later stages by systolic dysfunction that progresses to decompensated heart failure, resulting in morbidities and mortality. The pathogenesis of diabetic cardiomyopathy is complex and multifactorial. Mechanisms that include impaired calcium handling, up-regulated renin-angiotensin system, increased oxidative stress, altered substrate metabolism, and mitochondrial dysfunction have been implicated. In the COVID-19 pandemic, patients with diabetes mellitus infected with SARS-CoV-2 have a poorer prognosis including mortality. In this talk, I shall share our recent research findings using human induced pluripotent stem cell technology to identify potential mechanistic pathway related diabetic cardiomyopathy, and the direct therapeutic effects of SGLT inhibitors in diabetic cardiomyopathy, and the pathogenic link between SARS-CoV-2 infection and direct myocardial damage. Furthermore, our cardiac magnetic resonance imaging data has shown that patients with diabetes and impaired left ventricular ejection fraction, dapagliflozin alleviates cardiomyopathic changes.

Myocardial Perfusion Imaging After Severe COVID-19 Infection Demonstrates Regional Ischemia Rather Than Global Blood Flow Reduction.

Background: Acute myocardial damage is common in severe COVID-19. Post-mortem studies have implicated microvascular thrombosis, with cardiovascular magnetic resonance (CMR) demonstrating a high prevalence of myocardial infarction and myocarditis-like scar. The microcirculatory sequelae are incompletely characterized. Perfusion CMR can quantify the stress myocardial blood flow (MBF) and identify its association with infarction and myocarditis.Objectives: To determine the impact of the severe hospitalized COVID-19 on global and regional myocardial perfusion in recovered patients.Methods: A case-control study of previously hospitalized, troponin-positive COVID-19 patients was undertaken. The results were compared with a propensity-matched, pre-COVID chest pain cohort (referred for clinical CMR; angiography subsequently demonstrating unobstructed coronary arteries) and 27 healthy volunteers (HV). The analysis used visual assessment for the regional perfusion defects and AI-based segmentation to derive the global and regional stress and rest MBF.Results: Ninety recovered post-COVID patients {median age 64 [interquartile range (IQR) 54–71] years, 83% male, 44% requiring the intensive care unit (ICU)} underwent adenosine-stress perfusion CMR at a median of 61 (IQR 29–146) days post-discharge. The mean left ventricular ejection fraction (LVEF) was 67 ± 10%; 10 (11%) with impaired LVEF. Fifty patients (56%) had late gadolinium enhancement (LGE); 15 (17%) had infarct-pattern, 31 (34%) had non-ischemic, and 4 (4.4%) had mixed pattern LGE. Thirty-two patients (36%) had adenosine-induced regional perfusion defects, 26 out of 32 with at least one segment without prior infarction. The global stress MBF in post-COVID patients was similar to the age-, sex- and co-morbidities of the matched controls (2.53 ± 0.77 vs. 2.52 ± 0.79 ml/g/min, p = 0.10), though lower than HV (3.00 ± 0.76 ml/g/min, p< 0.01).Conclusions: After severe hospitalized COVID-19 infection, patients who attended clinical ischemia testing had little evidence of significant microvascular disease at 2 months post-discharge. The high prevalence of regional inducible ischemia and/or infarction (nearly 40%) may suggest that occult coronary disease is an important putative mechanism for troponin elevation in this cohort. This should be considered hypothesis-generating for future studies which combine ischemia and anatomical assessment.

Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function.

AimsChronic heart failure with reduced ejection fraction remains a major health issue. To date, no reliable biomarker is available to predict reduced left ventricular ejection fraction (LV‐EF). We aimed to identify novel circulating biomarkers for reduced left ventricular function using untargeted serum metabolomics in two independent patient cohorts.Methods and resultsEchocardiography and non‐targeted serum metabolomics were conducted in two patient cohorts with varying left ventricular function: (1) 25 patients with type 2 diabetes with established cardiovascular disease or high cardiovascular risk (LV‐EF range 20–66%) (discovery cohort) and (2) 37 patients hospitalized for myocardial infarction (LV‐EF range 25–60%) (validation cohort). In the discovery cohort, untargeted metabolomics revealed seven metabolites performing better than N‐terminal pro‐B‐type natriuretic peptide in the prediction of impaired left ventricular function shown by LV‐EF. For only one of the metabolites, acisoga, the predictive value for LV‐EF could be confirmed in the validation cohort (r = −0.37, P = 0.02). In the discovery cohort, acisoga did not only correlate with LV‐EF (r = −60, P = 0.0016), but also with global circumferential strain (r = 0.67, P = 0.0003) and global longitudinal strain (r = 0.68, P = 0.0002). Similar results could be detected in the discovery cohort in a 6 month follow‐up proofing stability of these results over time. With an area under the curve of 0.86 in the receiver operating characteristic analysis, acisoga discriminated between patients with normal EF and LV‐EF < 40%. Multivariate analysis exposed acisoga as independent marker for impairment of LV‐EF (Beta = −0.71, P = 0.004).ConclusionsWe found the polyamine metabolite acisoga to be elevated in patients with impaired LV‐EF in two independent cohorts. Our analyses suggest that acisoga may be a valuable biomarker to detect patients with heart failure with reduced ejection fraction.

Left Ventricular Systolic Dysfunction Due to Atrial Fibrillation: Clinical and Echocardiographic Predictors

Background: Diagnosis of AF-induced cardiomyopathy can be challenging and relies on ruling out other causes of cardiomyopathy and, after restoration of sinus rhythm, recovery of left ventricular (LV) function. The aim of this study was to identify clinical and echocardiographic predictors for developing cardiomyopathy with systolic dysfunction in patients with atrial tachyarrhythmia. Methods: This retrospective study was conducted in a large tertiary care centre and compared patients who experienced deterioration of LV ejection fraction (EF) during paroxysmal AF, demonstrated by precardioversion transoesophageal echocardiography with patients with preserved LV function during AF. All patients had documented preserved LVEF at baseline (EF >50%) while in sinus rhythm. Results: Of 482 patients included in the final analysis, 80 (17%) had reduced and 402 (83%) had preserved LV function during the precardioversion transoesophageal echocardiography. Patients with reduced LVEF were more likely to be men and to have a more rapid ventricular response during AF or atrial flutter (AFL). A history of prosthetic valves was also identified as a risk factor for reduced LVEF. Patients with reduced LVEF also had higher incidence of tricuspid regurgitation and right ventricular dysfunction. Conclusion: In ‘real-world’ experience, male patients with rapid ventricular response during paroxysmal AF or AFL are more prone to LVEF reduction. Patients with prosthetic valves are also at risk for LVEF reduction during AF/AFL. Finally, tricuspid regurgitation and right ventricular dysfunction may indicate relatively long-standing AF with an associated reduction in LVEF.

Abstract 9380: Rescuing Mitochondrial Fusion/Fission Balance Mitigates Oxidative Stress, Myocardial Injury and Apoptosis in Rats with Doxorubicin-induced Cardiotoxicity

Introduction: Doxorubicin (DOX) has been an extensively used chemotherapeutic drug in handling a wide range of cancers. Cardiotoxicity induced by DOX is a serious adverse effect of oncologic therapy. Although mitochondrial dynamic modulators including mitochondrial fission inhibitor (Mdivi-1) and fusion promoter (M1) have been shown as potential therapeutic remedies to treat various cardiovascular disorders, the cardioprotective effects of Mdivi-1 and M1 in DOX-induced cardiotoxicity is not known. Hypothesis: Mdivi-1 and M1 treatments reduce oxidative stress, myocardial injury, and programmed cell death by apoptosis, leading to improved left ventricular (LV) function in rats with DOX-induced cardiotoxicity. Methods: Male Wistar rats (n=20) were injected with either DOX (3 mg/kg, 6 doses, n=5) or 3% DMSO in NSS (n=5) as a control. In the DOX group, DOX-treated rats were received one of the following treatments: 1) 3% DMSO in NSS (n=5), 2) Mdivi-1 (1.2 mg/kg/day, n=5), 3) M1 (2 mg/kg/day, n=5). All treatments were given to the rats via intraperitoneal injection for 30 days beginning simultaneously with the first DOX injection. LV function, cardiac tissue malondialdehyde (MDA), serum cardiac troponin-I (c-TnI), and cleaved caspase-3 (CC3) protein levels were determined. Results: Injection of DOX markedly increased cardiac MDA, c-TnI, and CC3 levels (Fig. 1A-D). Impaired left ventricular ejection fraction (67% for DOX vs. 91% for control) was observed. Mdivi-1 and M1 co-treatment remarkably reduced the levels of MDA, c-TnI, and CC3, leading to increased LVEF from 67% in DOX to 89% in Mdivi-1 and 90% in M1, respectively (Fig. 1A-D). Conclusions: Mitochondrial fission inhibitor and fusion promoter effectively protected the heart from DOX-induced cardiotoxicity through suppression of oxidative stress, myocardial injury, and apoptosis. These findings indicate the mitochondrial dynamics as novel therapeutic targets in preventing Dox-induced cardiotoxicity.

Incidence, Predictive Factors, and Prognostic Impact of Right Ventricular Dysfunction Before Transcatheter Aortic Valve Implantation

Right ventricular dysfunction (RVD) is considered to be a late marker of aortic stenosis. However, there is a lack of consensus regarding the incidence, prognostic impact, and evolution of RVD in patients treated with transcatheter aortic valve implantation (TAVI). All patients treated with TAVI for severe aortic stenosis were included in a prospective single-center database. Patients who had a quantitative assessment of right ventricular (RV) function including tricuspid annular plane systolic excursion (TAPSE) and/or Doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S' wave) measurements were eligible for this study. RVD was defined as TAPSE <17 mm or S' <9.5 cm/s if TAPSE was not available. Between 2014 and 2019, 503 patients with RV function assessment were included. The incidence of RVD before TAVI was 18.7%. Predictors of RVD were diabetes (p=0.03), atrial fibrillation (p=0.001), impaired left ventricular ejection fraction (p <0.0001), left ventricular dilatation (p=0.007), and previous cardiac surgery (p=0.002). Long-term survival was worse in patients with RVD before TAVI compared with those without RVD (hazard ratio 1.97, 95% confidence interval 1.1 to 3.4, p=0.01). One year after TAVI, 58.7% of patients with baseline RVD had normal RV function and had similar outcomes as compared with those without RVD at baseline. In contrast, patients with persistent RVD had the worst prognosis. In conclusion, RVD is not rare and has a deleterious prognostic impact in patients treated with TAVI. Recovery of normal RV function is frequent after TAVI, whereas persistence of RVD is associated with poor outcomes.