Ventricular Outflow Tract Research Articles

Gender-related differences in clinical characteristics of patients with hypertrophic cardiomyopathy in our city

Abstract Background Female patients with hypertrophic cardiomyopathy (HCM) tend to display a higher rate of heart failure as well as lower survival compared to male patients. Despite this, gender-related differences in the clinical characteristics of HCM patients remain unclear. Methods and Aim Consecutive HCM patients were prospectively enrolled at a tertiary referral center. The primary objective of this study was to investigate and emphasize gender differences in clinical characteristics including imaging and laboratory parameters. Results Between May 2018 and January 2024, a total of 301 HCM patients were included, of which 41.9% were female (n=125). Female patients were significantly older and more symptomatic than male counterparts (59 years [IQR 47-67] vs. 53 years [IQR 39-61], p=0.001; New York Heart Association functional class ³III: 28.8% vs. 17.6%, p=0.002, respectively). No significant differences in body mass index were found (28.4 kg/m² [IQR 24.9-31.6] vs. 28.4 kg/m² [IQR 25.9-31.8], p=0.8). With respect to echocardiographic parameters, although interventricular septal thickness was comparable (19.0 mm [IQR 16.0-22.0] vs. 19.5 mm [IQR 17.0-22.0], p=0.4) left atrial as well as right atrial volume index were higher in women (30.0 cm³/m² [IQR 27.0-35.0] vs. 27.0 cm³/m² [IQR 24.0-30.0], p<0.001; 27.1 cm³/m² [IQR 25.4-29.3] vs. 24.7 cm³/m² [IQR 22.5-28.2], p<0.001). These findings were further supported by elevated filling pressures in female patients reflected by E/e’ ratio (16 [IQR 14-22] vs. 10 [IQR 9-12], p<0.001). Moreover, these patients showed more frequent left ventricular (LV) outflow tract obstruction (50% vs. 33%, p=0.029) which is accompanied by a slightly higher LV ejection fraction compared to men (69% [IQR 62-74] vs. 62% [IQR 55-67], p=0.004). In terms of cardiac biomarkers, female HCM patients presented with higher levels of serum N-terminal pro brain natriuretic peptide (671 pg/ml [IQR 333-1613] vs. 357 pg/ml [IQR 115-959], p<0,001) as well as lower concentrations of serum creatinine (0.84 mg/dl [IQR 0.75-0.95] vs. 0.98 mg/dl [IQR 0.87-1.15], p<0.001) whereas no differences regarding high-sensitive troponin-T levels were observed. Conclusion This single-center analysis illustrates profound gender-related differences among HCM patients in Vienna. Female patients tend to present in a more advanced clinical status, rather reflecting the phenotype of heart failure with preserved ejection fraction. Whether these findings should prompt an early HCM diagnosis in female patients with unspecific symptoms, or may result in early treatment initiation of e.g. sodium-glucose-transporter 2 inhibitors, should be part of future research.

Pulmonary valve acceleration fraction as a novel echo parameter to evaluate systolic pulmonary artery pressure during exercise echocardiography

Abstract Background/Introduction Long-COVID is a disabling chronic condition. Some patients have features of exercise-induced pulmonary hypertension (PHT) but non-invasive assessment during exercise stress echo (SE) is often limited by absence of reliable jet of tricuspid regurgitation (TR). We aimed to investigate novel Doppler echo parameters elicited from right ventricular (RV) outflow tract to aid diagnosis of exercise induced PHT among patients referred to our centre with Long-COVID symptoms. Purpose We investigated the ratio of the pulmonary valve acceleration time (PV AccT) to RV ejection time (RV ET) to calculate the pulmonary acceleration fraction (PV AccT/RV ET), thereby adjusting to heart rate. To identify its utility to estimate pulmonary artery pressure (PASP) during SE we correlated the PV AccT/RV ET and the TR-estimated RV systolic pressure (RVSP) in patients referred for evaluation of exercise-induced PHT in Long-Covid patients. Methods We developed a dedicated Covid-19 SE protocol to assess RV and pulmonary hemodynamics. From November 2022 to February 2023 all consecutive patients with Long-COVID symptoms underwent supine bike exercise with 3-min increments of workload of 25W. We did not evaluate the inferior vena cava during exercise, therefore estimated pressures from maximal TR jet velocities only. Results We enrolled 93 consecutive patients. The mean age was 50.1 years, 42.9% were female. No patients had RV impairment or RVSP >40mmHg at baseline. The average exercise time was 12.4 minutes, only 33% achieved the sub-maximum target heart rate (THR), in 50/93 (53.7%) reasons for termination were recorded as shortness of breath. The pulmonary acceleration fraction could be recorded in every patient at rest and at stress, while 20/92 (21.7%) patients had insufficient spectral Doppler profile of TR to estimate RVSP. The PV acceleration fraction was correlated with the available RVSPs during exercise (Spearman’s ϱ -0.446 (95% CI -0.606- -0.251[p<0.0001]). ROC analysis indicated a pulmonary acceleration fraction ≤0.44 was associated with the maximum Youden index to discriminate an increase in RVSP >20mmHg during exercise (AUC =0.731 [p<0.001]) with a sensitivity and specificity of 70.0% and 80.0%. In logistic regression analysis, a PV acceleration fraction ≤0.44 was independently associated with an increase in RVSP>20mmHg during exercise independently of age, gender and baseline LVEF, LVEDV, TAPSE and baseline RVSP (p<0.001). Conclusions Significant proportion of Long-COVID patients are limited by symptoms and not able to achieve THR during exercise. PV Acc T/ PV ET correlates well to RVSP and can be used to estimate PA pressure. A threshold of 0.44 appears independently associated with a benchmark of PA systolic pressure increase of >20mmHg. Further studies needed to evaluate this new marker of pulmonary hypertension in other group of patients.

Association between left ventricular outflow tract velocity time integral, ejection fraction, clinical characteristics, and mortality in an undifferentiated cohort of hospitalised patients

Abstract Background Left ventricular ejection fraction (LVEF) is commonly used to predict mortality in heart failure patients. However, LVEF is dependent on factors including preload, afterload, contractility, heart rate and measurement accuracy. Recently, left ventricular outflow tract velocity time integral (LVOT VTI) has been shown to confer additional prognostic value in both patients with advanced heart failure and patients hospitalised with heart failure with preserved ejection fraction. Purpose We evaluated the association between LVOT VTI, LVEF, clinical characteristics and mortality in an undifferentiated cohort of hospitalised patients. Methods All hospitalised patients who underwent echocardiogram between January – March 2021 were identified from a single-centre tertiary hospital database. Baseline characteristics, echocardiographic parameters, biomarkers, and mortality at 24 months were collected. Patients were categorised into LVOT VTI tertiles (> 19cm, 13.1 – 18.9cm, < 13cm) and LVEF tertiles (> 50%, 40-50%, < 40%) for analysis; p<0.05 was considered significant. Results Altogether, 653 patients comprising 370 (57%) with LVOT VTI > 19cm, 228 (35%) with 13.1 - 18.9cm, and 55 (8%) with < 13cm were included. There were 183 (28%) deaths. Mortality was associated with increased age (75.6 + 13.5 years vs 64.9 + 16.8 years, p<.0001), high-risk echocardiographic features including increased left atrial size (45.4 + 22.7ml/m² vs 35.8 + 14.9 ml/m², p<.001), E/e’ (14.8 + 8.7 vs 10.4 + 4.3, p<.001), reduced LVEF (51.7 + 15% vs 55.9 + 12%, p=.005) and tricuspid annular plane systolic excursion (TAPSE; 2 + 0.5cm vs 2.1 + 0.7cm, p=.001), and biomarkers including haemoglobin (99 + 45g/L vs 117 + 46g/L, p<.001), albumin 28 + 10g/L vs 32 + 10g/L, p<.001), elevated N-terminal pro brain natriuretic peptide (5126 + 5997ng/L vs 2035 + 3569ng/L, p<.0001), troponin (191 + 1301ng/L vs 102 + 306ng/L, p=.008) and creatinine (152 + 165µmol vs 86 + 99µmol, p<.001) levels on admission. Whilst there was no significant difference between LVOT VTI and mortality (z=-1.73, p=0.083) there was a significant positive relationship between LVOT VTI and LVEF (r [651] =0.49, p<.001). Further, there was a significant association between death and both LVEF tertiles (X2 [2, N=653] = 19.63, p<.0001), and LVOT VTI tertiles (X2 [2, N=653] = 9.05, p=.011). However, small subset analyses revealed similar mortality rates for the lowest LVEF LVOT VTI tertile (46%, n=55), lowest LVEF tertile (46%, n=87), and when combined (50%, n=32). Conclusion In an undifferentiated cohort of hospitalised patients, reduced LVOT VTI and LVEF are both associated with increased mortality. However, LVOT VTI does not appear to outperform LVEF in being associated with mortality.

Skeletal and respiratory muscle weakness contributes to decreased exercise capacity in hypertrophic cardiomyopathy

Abstract Background and Aims Although decreased exercise capacity (due to dyspnea or angina-like symptoms) constitutes the fundamental characteristics of hypertrophic cardiomyopathy (HCM), the pathophysiology of these symptoms remains only partly understood. We investigated clinical and functional determinants of decreased exercise capacity in a broad range of HCM patients irrespective of primary disease aetiology (either genetic disorder or e.g. infiltrative phenocopies in the course of cardiac amyloidosis), overt heart failure (HF) and the presence of haemodynamically significant left ventricular outflow tract obstruction (LVOTO). Further, we deterimined the contribution of skeletal and respiratory muscle weakness to decresed exercise capacity. Methods We analyzed clinical data and functional assessments (skeletal and respiratory muscle strength, physical fitness) in relation to symptomatology and sub-maximal exercise capacity in 82 clinically stable patients with HCM (females: 32 %; age: 62±16 years; left ventricular ejection fraction [LVEF] 59±7%; intraventricular septum wall thickness [IVS] 19±4 mm; median plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 818 pg/mL [lower and upper quartile: 208-1917]; New York Heart Association [NYHA] class 0/I/II/III: 38/18/33/11 % [0 indicates no HF]; significant LVOTO: 29%). Results HCM patients with more severe symptomatology (NYHA class II-III vs 0-I) were older, had more frequently significant LVOTO and greater comorbidity burden, and had higher NT-proBNP and worse estimated renal function (all p≤0.03). Gender distribution, percentage of beta-blocker therapy and implanted device, body mass index, major echocardiography parameters (including LVEF, left ventricular end-diastolic diameter and IVS), high-sensitive (hs) cardiac troponin type I and hs-C-reactive protein were comparable in these 2 groups of subjects (all p>0.05). In multivariable linear regression models more advanced age, higher circulating natriuretic peptides (NT-proBNP) and previous coronary revascularization were independent predictors of more advanced NYHA class (standardized β-coefficient=0.30, p<0.01; β=0.27, p<0.01; and β=0.22, p<0.05; respectively). Similarly, more advanced age, female sex and higher NT-proBNP were independent correlates of shorter distance in 6-minute walking test (6MWT) (β=-0.46, p<0.001; β=-0.26, p<0.001; and β=-0.36, p<0.001; respectively). All analyzed muscle parameters (including respiratory muscle strength parameters) and objective measures of physical fitness (Functional Fitness Test for older adults) remained independently associated with 6MWT distance (all p<0.001) when adjusted for aforementioned clinical and laboratory correlates of 6MWT. Conclusions Muscle weakness and low physical fitness are related to decreased exercise capacity in HCM and may be potential therapeutic targets to alleviate disease symptoms also in non-obstructive HCM phenotype.

Serial changes in left and right ventricular global longitudinal strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: insights from VALOR-HCM trial

Abstract Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM phase 3 randomized, double-blind, placebo-controlled clinical trial demonstrated that mavacamten, reduces the need for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients and symptoms. As a cardiac myosin inhibitor, mavacamten’s mechanism of action reduces myocardial hypercontractility. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function and can complement left ventricular ejection fraction (LVEF). Objective We sought to assess serial changes in LV and right ventricular (RV)-GLS in patients enrolled in the VALOR-HCM study. Methods VALOR-HCM included 112 symptomatic obstructive HCM patients (mean 60 years, 51% male, LVEF 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo crossed over to mavacamten (n=52) from week 16-56 (40-week exposure). LV and RV-GLS assessment was performed according to the current American and European guideline recommendations using a vendor-neutral post processing software. Non-foreshortened apical (4, 3 and 2-chamber) views were used to obtain peak value of LV-GLS. For RV-GLS, RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. Results Serial changes in LVEF, average LV-GLS, and RV-GLS (4-chamber and free wall) from baseline to week 56 are shown in the Figure. Despite preserved LVEF at baseline, average baseline LV-GLS was abnormal. There were significant and continued improvements in LV-GLS in the total group from baseline to week 56. 12 patients had transient reduction in LVEF (<50%) requiring temporary drug interruption (permanent discontinuation in 3). The LV-GLS in this subgroup was worse at baseline compared to the total study population, with no significant worsening from baseline through week 56. In the overall population, excluding these 12 patients, LV-GLS demonstrated an improvement sustained through week 56. Both free wall and 4-chamber RV-GLS were abnormal at baseline and remained unchanged from baseline to week 56. Conclusions In the VALOR-HCM trial, despite hypercontractile LVEF at baseline, average baseline LV-GLS was worse than normal reference values. Treatment with mavacamten resulted in an improvement in LV-GLS from baseline through Week 56 (with no significant worsening of LV-GLS in the subgroup who experienced any reduction in LVEF <50%), suggesting a favorable long-term impact on regional LV systolic function due to the reduction of cardiac hypercontractility. Additionally, there was no significant detrimental impact on RV systolic function on serial GLS assessment.Serial changes in LV and RV GLS in VALOR

Clinical application of biomarkers in obstructive hypertrophic cardiomyopathy: insights from SEQUOIA-HCM

Abstract Background Multiple studies show that circulating cardiac biomarkers, N-terminal pro-B type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin I (hs-cTnI) are associated with key pathophysiological processes and clinical outcomes in obstructive hypertrophic cardiomyopathy (oHCM). Herein we describe the impact of aficamten on cardiac biomarkers in SEQUOIA-HCM (NCT05186818). Purpose In this pre-specified analysis, we describe associations between baseline NT-proBNP and hs-cTnI concentrations and assess the relationship between changes after treatment with aficamten and trial endpoints. Methods Patients with oHCM in NYHA Class II-III, were randomized 1:1 to 24 weeks of daily aficamten (5–20 mg, n=142) or placebo (n=140). Aficamten dose was adjusted to achieve Valsalva left ventricular outflow tract gradient (LVOT-G) <30 mmHg while maintaining left ventricular ejection fraction (LVEF) ≥50%. Peak oxygen consumption (pVO2) was measured by cardiopulmonary exercise testing at baseline and week 24. Cardiac biomarkers were measured at baseline, each dose titration (weeks 2, 4, and 6), every 4 weeks during treatment and after 4 weeks drug washout. Multivariable regression analysis was used to identify significant predictors of baseline biomarker values. Joint modeling and mediation analysis was used to determine how much of the treatment effect was indirectly mediated by NT-proBNP and hs-cTnI. Results In 282 symptomatic oHCM patients (mean age 59 years, 41% female), the median (IQR) NT-proBNP was 788 ng/L (346, 1699) and hs-cTnI was 12 ng/L (9, 27). At baseline, LVOT-G modestly correlated with NT-proBNP, rho = 0.26 (p<0.001) but not hs-cTnI, rho = 0.06 (p=0.36). Predictors of baseline biomarker values are summarized in Table 1. Compared to placebo, aficamten treatment was associated with an early relative reduction from baseline at week 8 in NT-proBNP (-79% (95% CI -83%, -76%, p<0.001) and in hs-cTnI -41% (-49%, -32%), p<0.001. This magnitude of change persisted to week 24 with biomarker return to baseline after aficamten washout (Figure 1). The mediation analysis suggested that NT-proBNP reduction over the 24-week treatment period reflected 101% (41%, 195%) of aficamten’s effect on pVO2. In contrast hs-cTnI reduction reflected 3% (-18%, 30%) of aficamten’s effect on pVO2. Conclusions Concentrations of NT-proBNP and hs-cTnI are associated with clinically relevant echocardiographic variables in oHCM. Compared with placebo, aficamten treatment markedly reduced plasma NT-proBNP and hs-cTnI concentrations, evident from week 2 and persisting until the end of treatment. NT-proBNP reduction may link LVOT-G with reduced exercise capacity in oHCM. These data support the use of biomarkers as a tool for managing patients with oHCM in order to monitor response to aficamten therapy.Effect of aficamten on biomarkersPredictors of baseline biomarkers

Hemodynamic effects of right and biventricular pacing during exercise in hypertrophic obstructive cardiomyopathy

Abstract Background One third of patients with hypertrophic cardiomyopathy present with dynamic left ventricular outflow tract obstruction (LVOTO), referred to as hypertrophic obstructive cardiomyopathy (HOCM). Symptomatic treatment aims at reducing LVOTO with either medications, invasive septal reduction, or pacing. The importance of pacing site is unclear, and effects of pacing during physical activity have not been investigated. Purpose To determine the effect of right ventricular (RV) and biventricular (BiV) pacing, respectively, on LVOTO and cardiac output (CO) during exercise in patients with HOCM. Methods Patients with symptomatic HOCM, sinus rhythm, and no bundle branch block, scheduled for alcohol septal ablation (ASA), were eligible for inclusion. The day before ASA, we placed temporary pacing leads in the right atrium, the RV apex, and on the left ventricle’s lateral wall via the coronary sinus. LVOTO was assessed by echocardiography, and CO was measured by thermodilution with a pulmonary artery catheter. Patients performed supine cycling for 2 minutes until heart rate (HR) increased ≥20 bpm. We measured LVOTO and CO in sinus rhythm, and during cycling with atrial sensed RV pacing, and atrial sensed BiV pacing. The order of pacing sites was randomized, and the personnel performing echocardiography and CO measurements were blinded to the order of pacing. Results We included six patients (54±15 years) with a mean maximal left ventricular wall thickness of 16.7±1.8 mm. Resting LVOTO was 55.7±30.9 mmHg. The figures show LVOTO and CO in sinus rhythm (HR 85±10 bpm), RV pacing (HR 90±10 bpm), and BiV pacing (HR 91±9 bpm) during supine cycling. The LVOTO declined from 56±34 mmHg in sinus rhythm to 27±12 mmHg and 25±5 mmHg respectively for atrial sensed RV and BiV pacing. CO remained unchanged during sinus rhythm (9.0±1.2 L/min), atrial sensed RV pacing (9.0±1.7 L/min), and BiV pacing (8.9±1.5 L/min). Conclusion In this ongoing study evaluating cardiac pacing in HOCM, preliminary data indicate that both RV and BiV pacing are effective in reducing LVOTO during exercise, without compromising CO.

Is unsatisfactory outcome of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy predictable?

Abstract Background Alcohol septal ablation (ASA) has been introduced for left ventricular outflow tract gradient (LVOTG) reduction in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, some patients may not profit from ASA. Thus, we identified characteristics of patients with unsatisfactory outcome of ASA in a large single-center cohort. Methods Consecutive ASAs between 1997 and 2023, performed at our institution, were retrospectively enrolled. Those ASAs performed in patients with missing follow-up (FU), previous septal reduction therapy (SRT), and atypical HOCM were excluded. Patients with unsatisfactory outcome (PUO) were defined as continuing to meet the guideline criteria for SRT (NYHA ≥III or NYHA ≥II with exertional syncope and resting/exercise-induced LVOTG ≥50mmHg). PUO were compared to patients with good outcome (PGO). Results are expressed in % or median and interquartile range (IQR). Pre-procedural predictors of poor hemodynamic outcome were identified using logistic regression analysis. Results 65 of 1003 patients were PUO (6.5%). Those were younger (48.0 years [40.5-61.8] vs. 57.0 years [IQR 47.0-67.0] in PGO; p=0.0030), more often reported syncope at baseline (35.4% vs. 22.2% in PGO; p=0.0214), and had lower body-mass-index (26.4kg/m2 [23.8-29.2] vs. 27.7kg/m2 [25.2-23.1] in PGO; p=0.0160). In PUO, resting LVOTG was higher at baseline (53.0mmHg [24.5-82.0]) than in PGO (40.0mmHg [22.0-75.0]; p=0.0292; Table 1). Differences in sex, family history of sudden cardiac death, dyspnoea, medication, and interventricular septum diameter (IVSD) were not observed at baseline (all p>0.05; Table 1). Age (OR 1.023; CI: 1.005-1.042; p=0.0129), syncope at baseline (OR 1.890; CI: 1.049-3.324; p=0.0296), and BMI (OR 1.072; CI: 1.007-1.145; p=0.0355) were found to independently influence poor hemodynamic response to ASA using multiple logistic regression controlling for confounders. However, sex, baseline IVSD, and LVOTG were not found to influence poor hemodynamic outcome (p>0.05). There were no differences with regard to the number of embolized branches (1 in both groups), the size of the balloon used to cover the septal branch (1.5mm in both groups), the volume of ethanol (PUO: 1.4ml [1.0-2.0]; PGO: 1.5ml [1.2-2.0]), or creatine kinase release (PUO: 879.0U/l [375.0-1187.0]; PGO: 842.0U/l [501.5 - 1234]) (all p>0.05). At 6-months-FU, PUO had significantly higher IVSD (18.0mm [13.5-22.0] vs. 16.0mm [12.0-19.0] in PGO; p=0.008), higher resting LVOTG (31.0mmHg [20.0-55.5] vs. 14.0mmHg [10.0-22.0] in PGO; p<0.0001) and higher exercise-induced LVOTG (105.0mmHg [84.5-143.0] vs. 35.0mmHg [22.0-64.0] in PGO; p<0.0001). Conclusion ASA was overall effective with only few patients experiencing unsatisfactory outcome. Syncope, age, and BMI were found predicting poor hemodynamic outcome.Baseline characteristics

Sex differences in paediatric onset hypertrophic cardiomyopathy

Abstract Background Hypertrophic Cardiomyopathy (HCM) is a heterogeneous disease characterised by age related incomplete penetrance and variable long term outcomes. Sex differences have been described in both the clinical phenotype and natural history of adults with the disease, which have been attributed to both biological (eg sex hormone effect) and non-biological (eg societal and cultural effects) factors. It is unknown if similar sex differences exist in childhood-onset HCM. Purpose This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM. Methods Retrospective cohort study from an international registry of patients diagnosed under the age of 18 years with HCM. Patients with syndromic disease (RASopathy syndromes, inborn errors of metabolism, neuromuscular disease) were excluded. Sex differences in baseline characteristics and clinical outcomes were described. Primary outcomes were all-cause mortality or cardiac transplantation, Major Arrhythmic Cardiac Event (MACE) and heart failure event (defined as heart failure death or cardiac transplantation) Results Of 1262 patients, 851 (67.4%) were male (median age 11 yrs (IQR 7.4, 14.4) vs 11.1 (IQR 6.9, 14.0) in females, p=0.0312). Female patients were more likely to have a sarcomeric variant identified (n=208, 85.6% vs 388 (79.4%), p=0.041) despite equivalent genetic testing utilisation between sexes. Female patients were more likely to have severe heart failure symptoms (NYHA 3 or 4) (n=19, 6.1% vs n=20, 2.5% p value 0.030) but there was no difference in the proportion on medical therapy (male n=328, 39.7%, female n=167, 41.8, p value 0.476). The clinical phenotype in terms of degree of hypertrophy, left atrial size and left ventricular outflow tract gradient did not differ by sex. Over a median follow up of 5.2 years (IQR 2.4, 9.9) all-cause mortality or cardiac transplantation did not vary by sex but females were more likely to experience a heart failure event (females 0.6/100,000 pt years (95% CI 0.39-0.92) vs males 0.32/100,000 pt years (95% CI 0.21 – 0.50), hazard ratio 1.89, p value 0.0467). The incidence of MACE did not differ by sex but there was a trend towards higher implantable cardioverter defibrillator implantation in females (n=123, 30.7% vs n=210, 25.4%, p value 0.051). Conclusions For the first time, this study has shown sex differences in paediatric-onset hypertrophic cardiomyopathy. Despite no difference in baseline clinical phenotype, young female patients are more likely to experience heart failure symptoms and heart failure events over follow up. Further studies are required to explore the underlying mechanisms for these observed differences.Table summarising outcomes by sexSurvival free from heart failure

Differentiation of severe from non-severe mitral stenosis with dimensionless index and its prognostic implications in patients with rheumatic mitral stenosis

Abstract Introduction Accurate identification of the severity of rheumatic mitral stenosis (MS) commonly relies on measurement of mitral valve area (MVA) by transthoracic echocardiography (TTE). The dimensionless index (DI) of mitral valve (MV) was recently shown to be useful in identifying severity of degenerative MS. It is uncertain if DI MV is useful in rheumatic MS. Purpose We aimed to validate the DI MV in rheumatic mitral stenosis, identify threshold values of the DI MV for the accurate identification of severe and non-severe rheumatic MS, and study its association with clinically significant outcomes. Methods We studied DI MV in 406 cases of rheumatic MS, with 174 cases in a derivation cohort , 121 cases in a TTE validation cohort, and 111 cases in a transoesophageal echocardiography (TEE) validation cohort. Outcome data were collected in the derivation and TTE validation cohorts. DI MV was calculated by dividing the left ventricular outflow tract pulsed-wave Doppler time-velocity integral (TVI) by the MV continuous-wave Doppler TVI. Results In the derivation cohort, ROC analysis showed that MV DI was significantly associated with MS severity (AUC = 0.838, 95% CI, 0.780-0.897, p<0.001) but no threshold value was able to identify severe MS (MVA ≤ 1.5 cm2) with both sensitivity and specificity greater than 80%. DI MV ≤ 0.34 had the best combination of sensitivity and specificity (78.5% and 75.8% respectively). However, with an approach using two threshold values, namely DI MV ≤ 0.25 to identify severe MS and DI MV ≥ 0.40 to identify non-severe MS, both values showed a high specificity of 93.7%. When tested in the validation cohorts, these values have similar high specificity for identifying severe (93.8%) and non severe MS (91.4%). DI MV was univariately significant (HR = 0.075, 95% CI 0.0215-0.378, p=0.002) in Cox regression analysis for a composite outcome of death and MV intervention. Multivariate analysis incorporating age, sex, DI MV, pulmonary artery systolic pressure (PASP) and left ventricular ejection fraction (LVEF) showed that age, DI MV and PASP were independently associated with the composite outcome. Conclusion While not a replacement for MVA in the assessment of MS severity, the DI MV can rule-in or rule-out severe MS with a high specificity and is useful as a complementary tool in the integrative assessment of MS severity. DI MV is independently associated with composite outcomes of death and MV intervention.Receiver operating characteristic curveSensitivity and Specificity of DI MV

Effect of stereotactic body radiation therapy on left ventricular diastole function in symptomatic patients with hypertrophic obstructive cardiomyopathy

Abstract Background We applied stereotactic body radiotherapy (SBRT) for the first time in the treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM), and significant improvements in symptoms and diastolic function were observed after treatment. Objectives To evaluate the impact of SBRT on cardiac structure, function, and clinical indicators in patients with HOCM. Methods This study included 12 drug-refractory symptomatic HOCM patients (6 who underwent SBRT and 6 who received pharmacological treatment alone) and conducted a retrospective analysis of their clinical data. Transthoracic echocardiography was used to assess various ultrasound parameters, including interventricular septal thickness, left ventricular outflow tract diameter, peak pressure gradient and diastolic function before treatment and at 1, 3, and 6 months after treatment. Additionally, assessments were made for symptoms; laboratory test results (NT-proBNP, cTnT, CK-mb, and CRP); 6-minute walk test results; New York Heart Association (NYHA) functional classification; and Kansas score before and 6 months after treatment. Results HOCM patients showed significant improvement in mitral valve systolic anterior motion after SBRT. Compared to that at baseline, the interventricular septum thickness gradually decreased at 1, 3, and 6 months after treatment (-8.8%, -8.0%, -14.4%, respectively) (P<0.05). Compared to those in the drug group, the left ventricular diastolic function and structural parameters, including the interventricular septum thickness (mean change from baseline of -3 mm [95% CI: -5.2 to -0.8 mm] and 1.3 mm [95% CI: 0.5 to 2.2 mm]; P<0.05), and the LA GLS (change of 2.1% [-0.03% to 4.2%] and -0.9% [-3.1% to 1.3%]; P<0.05), were significantly improved in HOCM patients at 6 months posttreatment. Similarly, the clinical indicators, including KCCQ, increased from baseline (61 (range, 47.3-70) to 84 (range, 70-89.5) at 6 months posttreatment (P<0.05), and the 6-minute walk test score increased from 187 meters (range, 50-370) to 401 meters (range, 280-540) (P<0.05). Conclusion SBRT significantly improved left ventricular diastolic function and reduced interventricular septum thickness in HOCM patients. Symptoms, exercise capacity and clinical indicators improved after SBRT in HOCM patients.

Aficamten in patients with obstructive hypertrophic cardiomyopathy: an integrated safety analysis

Abstract Background Aficamten is a next-in-class, oral, selective cardiac myosin inhibitor targeting the hypercontractility underlying hypertrophic cardiomyopathy (HCM). It relieves left ventricular outflow tract obstruction, improves exercise capacity, symptoms, quality of life, and cardiac biomarkers with a modest effect on left ventricular ejection fraction (LVEF). Purpose To present an integrated safety analysis from all aficamten trials to date. Methods Patients with obstructive HCM (oHCM) who received ≥1 dose of aficamten or placebo [PBO] in the phase 2 REDWOOD-HCM trial, phase 3 SEQUOIA-HCM trial, or the open-label extension FOREST-HCM were included. Results In the PBO-controlled pool of REDWOOD-HCM and SEQUOIA-HCM, 170 patients received aficamten and 153 PBO. In the cumulative (parent+extension) aficamten treated pool, 283 patients were analyzed from initial dose of aficamten or after enrollment in FOREST-HCM (100 PBO-to-aficamten). Overall, mean age was 59 years, 42% were female. In the PBO-controlled pool the mean cumulative follow up was 70.8 patient-years (py) on aficamten, and 66.3 py on PBO, and the total cumulative exposure period to aficamten was 205.2 py. The mean dose of aficamten in the cumulative pool was 12.6 mg/day. Treatment emergent serious adverse events (TESAE) occurred in 10 (5.9%) aficamten patients vs 14 (9.2%) PBO patients in the PBO-controlled pool, and in 24 (8.5%) aficamten patients in the cumulative pool. In the blinded phase, reported AEs were dizziness in 11 (6.5%) aficamten vs 3 (2%) PBO patients, syncope in 3 (1.8%) vs 4 (2.6%), dyspnea in 11 (6.5%) vs 8 (5.2%) and hypertension in 11 (6.5%) vs 4 (2.6%). Site-read LVEF <50%, all resulting in down-titration occurred in 9 (5.3%) aficamten patients [exposure adjusted incidence rate (EAIR) 11.2 per 100 py] and 1 (0.7%) PBO patient (EAIR: 1.3 per 100 py), and in 11 (3.9%) aficamten patients in the cumulative pool (EAIR: 5.3 per 100 py). None of the LVEF <50% events in aficamten patients were associated with heart failure symptoms; 1 PBO patient with a low LVEF had an AE of peripheral edema. During the maintenance phase of the cumulative exposure pool, 1588 echocardiograms were performed, of which 11 (0.7%) led to dose reduction due to LVEF <50%, none resulted in discontinuation or treatment interruption. In the cumulative pool, 6 (2.1%) patients terminated treatment early, none due to aficamten-related AEs. New onset atrial fibrillation occurred in 4 (2.4%) aficamten (EAIR: 4.9 per 100 py) and 5 (3.3%) PBO patients (EAIR: 6.5 per 100 py). There were no deaths during the study period. Conclusions In this integrated safety analysis, aficamten had a safety profile similar to PBO and was consistent over an extended treatment period. There was a low incidence of LVEF <50%, none of which were associated with clinical sequalae, and all were successfully managed by dose reduction. Monitoring echocardiography in the maintenance phase yielded very few actionable results.

Mildly elevated left ventricular outflow tract gradients are associated with increased short term mortality in inpatients without septal hypertrophy

Abstract Background The significance of left ventricular outflow tract gradients (LVOTG) on the clinical outcomes of hypertrophic cardiomyopathy (HCM) has been well studied. An LVOTG of ≥ 30 mmHg is considered significant. However, mildly elevated LVOTG at rest in individuals without basal septal hypertrophy is sometimes encountered in the echocardiography laboratory and data on its association with survival in this group is lacking. Purpose Here we explore the association between LVOTG and short term all cause mortality in inpatients without basal septal hypertrophy. Methods We retrospectively reviewed 47,866 consecutive inpatients who had an echocardiography study during their hospital stay between March 2010 and February 2021 . After excluding cases with incomplete data (10,882) and patients with basal septal hypertrophy > 12 mm (9,486), we remained with 27,498 patients. Demographic, baseline clinical and echocardiographic characteristics were derived from electronic records. Mortality data was validated against the ministry of health national records. A binary logistic regression model for predicting 30-day mortality according to LVOTG dichotomized at each point was used. Then we divided the cohort into 4 LVOTG groups (0-6, 6-10, 10-20 and > 20 mmHg) and the same regression model was used to compare between the groups. Results The mean age in our cohort was 66 ± 17 years and 54% were male. The mean LVOTG was 4.2 ± 2.4 mmHg (Median 4 (IQR=3-5) and the mean left ventricular ejection fraction was 55 ± 9%. A binary logistic regression model showed that when different LVOTG cut-points were used, even a mildly elevated LVOTG predicted short-term survival in this population (figure 1). We then divided our cohort into 4 groups based on LVOTG. There were 24,703 (90%) patients in group 1, 2549 (9%) in group 2, 201 (1%) in group 3 and 25 (0.1%) individuals in group 4. Patients in groups 1 and 2 were younger, had higher hemoglobin levels, lower C-reactive protein (CRP) levels, mildly lower septal thickness, and lower left ventricular ejection fraction compared to the groups with higher LVOTG (table 1). We then applied the same multivariate binary regression model to predict short term mortality with group 1 as a reference. The hazard ratio (HR) for group 2 was 1.3 (CI 95%: 1-1.6, p=0.03), for group 3 HR=2.8 (CI 95%: 1.6-5.1, p<0.001) and for group 4 HR=2.8 (CI 95%: 0.6-12.8, p=0.18). Conclusions We have shown in a large cohort of inpatients without basal septal hypertrophy that a mildly elevated rest LVOTG (6-10 and 10-20 mmHg) predicted all cause 30-day mortality. Patients in the elevated LVOTG groups were older with lower hemoglobin and higher CRP levels, but LVOTG remained an independent predictor in a multivariate regression model. This could potentially aid early detection of at-risk populations.Mortality at different LVOTG cut-pointsBaseline characteristics

Clinical characteristics and outcomes of patients with takotsubo syndrome and dynamic left ventricular outflow tract obstruction

Abstract Background Left ventricular outflow tract obstruction (LVOTO) is recognized as a serious complication of Takotsubo syndrome (TTS). However, its impact on patient prognosis remains insufficiently investigated. Purpose This study aimed to assess clinical characteristics and short- and long-term outcomes of patients with TTS complicated by LVOTO. Methods Patients with TTS were enrolled from the Takotsubo Italian Network (TIN). The primary outcome was the composite of acute heart failure, cardiogenic shock, and mortality during hospitalization. Secondary outcomes included the single components of the primary outcome and the occurrence of death or TTS recurrence during follow-up. Results Overall, 881 patients were included in the study [median age 72.0 (63.0–78.0) years; 91.3% female], with LVOTO detected in 59 patients (6.7%). Low diastolic blood pressure, ST-segment elevation, and moderate-to-severe mitral regurgitation were independently associated with occurrence of LVOTO. Propensity score weighting regression analysis revealed a significant higher risk of the primary outcome (OR, 2.99; 95% CI, 2.22–4.02), acute heart failure (OR, 2.19; 95% CI, 1.59–3.02), cardiogenic shock (OR, 4.56; 95% CI, 3.07–6.78), and in-hospital mortality (OR, 2.42; 95% CI, 1.13–5.21) in patients with TTS complicated by LVOTO. No significant association between LVOTO and long-term mortality or TTS recurrence was observed during follow-up. Conclusions In this real-world evidence study, LVOTO was detected in about 7% of TTS patients and was associated with a significantly higher risk of adverse events during hospitalization, including mortality. Early detection of LVOTO can aid in prognostic assessment and guide therapeutic management in patients with TTS.

Refining risk stratification in hypertrophic cardiomyopathy: the role of late gadolinium enhancement and syncope in predicting adverse outcomes

Abstract Background The presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is recognized as a significant marker of myocardial fibrosis and a predictor of adverse outcomes in hypertrophic cardiomyopathy (HCM). Nevertheless, the specific quantity of LGE that correlates with poor outcomes is still under debate. Therefore, this study sought to assess the combined impact of LGE presence and a history of syncopal events and its association with clinical prognosis. Methods Between May 2018 and June 2023, a total of 230 HCM patients was prospectively enrolled at our Medical University, a tertiary referral center. The primary endpoint was a composite of new-onset ventricular tachycardia (VT), appropriate ICD therapy, and all-cause mortality. Results Median age of enrolled patients was 56 (IQR 44-64) years and 40% (n=94) were female. Median interventricular septal thickness (IVS) was 21 (IQR 18–25) mm and 43 % (n=84) had significant left ventricular outflow tract obstruction (LVOTO). Over a median follow-up of 3.2 years, 30 patients (13%) met the composite endpoint. These patients had a significantly higher LGE quantity compared to the non-event group (1.1 % vs. % 9.0, P=0.012). An LGE threshold of 5.2% was identified as an optimal predictor of the composite endpoint, with an area under the curve of 0.72, which increased to 0.77 when including at least one syncopal event in medical history. LGE > 5.2% and/or syncope were independently associated with adverse outcomes after multivariable adjustment (Adj HR 7.26 [95%CI 2.54-20.72]). Furthermore, NTproBNP and hsTnT were associated with the presence of LGE or syncope (OR for a 1-unit increase in standardized log-transformed biomarker NTproBNP 3.35 [95%CI 1.42-10.85]; hsTnT 3.48 [95%CI 1.48-10.24], respectively). Interestingly, typically used variables for risk stratification, such as age, IVS or LVOT were not significantly associated with these cardiac biomarkers. Conclusion An extent of LGE > 5.2% and the history of at least one syncope are associated with unfavorable clinical outcomes in HCM patients. These findings call for detailed MRI appraisal and suggest adopting a holistic approach to accurately identify high-risk patients.

Mavacamten in a real-world hypertrophic cardiomyopathy population: how many may be eligible?

Abstract Introduction Mavacamten is a newly approved drug for obstructive hypertrophic cardiomyopathy (oHCM) and is currently being studied in non-obstructive HCM (nHCM). Our goal was to evaluate how often patients with oHCM and nHCM in a real-world cohort would be eligible for the main mavacamten trials: EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM. Methods Single-centre retrospective study enrolling consecutive patients with confirmed HCM, as per the 2023 ESC Guidelines, with at least yearly follow-up in our center, from 2017-2023. Key inclusion criteria from the three trials were considered: NYHA class II-III for all; obstructive forms (defined as peak left ventricle outflow tract [LVOT] gradient ≥50 mmHg at rest, after Valsalva manoeuvre or exercise) for EXPLORER-HCM and VALOR-HCM; left ventricular ejection fraction (LVEF) ≥55% for EXPLORER-HCM and MAVERICK-HCM; LVEF ≥60% and formal criteria for septal reduction therapy for VALOR-HCM, and NT-proBNP ≥300pg/mL for MAVERICK-HCM. Key exclusion criteria (estimated glomerular filtration rate [eGFR] <30mL/kg/1.73m2, QTc using the Fridericia’s formula >500ms, paroxysmal or intermittent atrial fibrillation present on screening electrocardiograph) were also considered. Results Overall, 410 patients were diagnosed with HCM, of whom 361 (88%) were alive at follow-up and included in the analysis: mean age of 63 ± 16 years, 196 (54%) were male, 272 (75%) with septal HCM and 60 (17%) with oHCM. According to the criteria of EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM, 35 (10%), 6 (2%) and 27 (7%) patients would be eligible for enrolment, respectively. In patients with oHCM, 35 (58%) would be eligible for the EXPLORER-HCM trial. In the overall cohort, 65 (18%) would have criteria for at least one of the trials. The main reasons for exclusion were as follows: 191 (53%) NYHA I, 43 (12%) with NYHA IV, 12 (3%) had a LVEF <55%, 8 (2%) had both HCM and infiltrative myocardial disease and/or moderate-to-severe aortic stenosis and 8 (2%) had an eGFR <30mL/kg/1.73m2. In patients with nHCM, 16 (5%) would have been excluded due to NT-proBNP <300pg/mL and 8 (3%) due to paroxysmal atrial fibrillation. Conclusion In a real-word HCM cohort, we found that approximately 1 in every 5 patients would have criteria for either of the mavacamten trials, with more than half of oHCM being potential candidates for the EXPLORER-HCM. The main reasons for non-eligibility were NYHA I and LVEF <55%.

Echocardiographic associates of impaired sleep quality in patients with anxiety and depression

Abstract Objective Sleep health, mental health and cardiovascular health are multidimensional constructs that are strongly associated with each other. Anxiety and depression are the most common psychiatric diseases in the community and frequently comorbid in routine clinical practice. This study sought to investigate whether there is an association between sleep quality and echocardiographic parameters in patients with anxiety and/or depression. Methods The clinical and instrumental find­ings of consecutive patients diagnosed with either of anxiety disorders and/or depressive disorders and underwent cardiac examination in our tertiary center on the same day were retrospectively reviewed. The diagnosis was made by a psychiatrist according to the criteria listed in the fifth edition of The Diagnostic and Statistical Manual of Mental Disorders. Afterwards, Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) were applied to patients to assess symptom severity and sleep quality, respectively. Subsequent to psychiatric examination, the patients underwent echocardiographic examination that includes two-dimensional conventional echocardiography, tissue doppler imaging (TDI) echocardiography, atrial conduction times, and left atrium (LA) volumes and functions. Results The final study population consisted of 167 patients and divided into two groups according to their PSQI score: PSQI<5 (normal sleep quality) (n=32) and PSQI≥5 (impaired sleep quality) (n=135). Aortic diameter, left ventricular (LV) end-systolic diameter, LV end-diastolic and -systolic volume, LV stroke volume and LV stroke volume index, LV outflow tract velocity–time integral (LVOT-VTI), and LA conduit volume calculations were significantly lower in patients with impaired sleep quality compared to patients with normal sleep quality. The other echocardiographic parameters including LV systolic functions, doppler and TDI echocardiography indices, atrial conduction times, atrial mechanical functions including LA function index (LAFI) were similar among groups. Correlation analysis yielded a negative, weak but statistically significant correlation between LAFI and PSQI score (r=-0.17, p=.030) (Figure 1A). Left intra-AEMD positively and significantly correlated with PSQI score at a weak level (r=0.16, p=.043) (Figure 1B). Aortic diameter, LV stroke volume index, LVOT-VTI and conduit volume were determined as echocardiographic parameters significantly associated with impaired sleep quality in univariate analysis. Among these parameters, only conduit volume remained as significant and independent associate of impaired sleep quality in multivariate logistic regression analysis (Odds ratio:0.91, 95% Confidence interval:0.85-0.98, p=.018) (Table 1). Conclusion There is an independent association between LA conduit volume and impaired sleep quality in patients suffering from anxiety and/or depressive disorders.Figure 1Table 1

Acute echocardiographic assessment of patients with ST-elevation myocardial infarction in detecting clinically hidden hemodynamic deterioration

Abstract Background Transthoracic echocardiography (TTE) offers an immediate non-invasive assessment of cardiac morphology and function that can be performed bedside. Acute TTE in the catheterization laboratory (cath.lab.) may be helpful to identify markers of subsequent development of cardiogenic shock (CS) in patients with ST-elevation myocardial infarction (STEMI) in addition to the previously validated ORBI risk score. This relationship has not been investigated thoroughly previously. Purpose To investigate the association between acute TTE estimates of left ventricular (LV) function prior to primary percutaneous coronary intervention (pPCI) in STEMI patients and pro-B-type natriuretic peptide (proBNP) as a proxy associated with of CS development. Method From September 2023 all non-CS STEMI patients at one tertiary heart center underwent acute bedside TTE in the cath.lab. and ORBI risk score assessing the risk of CS development aiming for inclusion of 500 patients. The 5 minutes TTE-protocol consisted of LV ejection fraction (EF), LV outflow tract velocity time integral (LVOT VTI), mitral inflow (E and E/A), mitral deceleration time, and mitral annular early diastolic velocity é lateral. The primary endpoint was proBNP measured 24 hours (h) after pPCI (12-36h) stratified in quartiles (Q4 vs. Q1-3). The correlation between proBNP and TTE measurements and proBNP and ORBI risk score was examined using univariate linear regression models. Results Until now 153 STEMI patients (mean age 64 years, 25% female) were studied. Anterior STEMI was present in 36%, and median time from cath. lab. arrival to first wire over the culprit lesion was 28 minutes (IQR 24; 37). Patients with high proBNP level (Q4 vs. Q1-3) had significantly higher heart rate (median 84 bpm vs. 72 bpm) and Killip Class>1 (16% vs. 0%) at admission, but similar lactate levels (1.8mM vs. 1.5mM), systolic blood pressure (130 mmHg vs. 137 mmHg), and out-of-hospital cardiac arrest (11% vs. 12%). Patients with high proBNP levels (Q4 vs. Q1-3) had significantly lower LVEF (35% vs. 50%), higher E/é lateral (median 11.4 vs. 7.9), and higher ORBI risk score (median 8 vs. 4). LVEF, LVOT VTI, E/é lateral, and ORBI risk score were significantly associated with proBNP (Figure 1). Two patients developed CS after the pPCI; one with high proBNP level Q4, and one deceased prior to proBNP measurement. Conclusion Acute TTE is an easy tool for assessment of the acute hemodynamic status in STEMI patients bedside in the cath.lab., and it can be without delaying time to revascularization. LVEF, LVOT VTI, E/é lateral, and ORBI were all parameters associated with increased levels of the hemodynamic biomarker proBNP, and may together with the ORBI risk score improve the assessment and risk stratification of STEMI-patients at risk of CS-development.Figure 1.

Clinical profile of patients undergoing percutaneous stellate ganglion block for electrical storm and association with antiarrhythmic efficacy

Abstract Background Percutaneous stellate ganglion block (PSGB) usage for patients with refractory ventricular arrhythmias (VAs) in form of electrical storm (ES) is in quickly expanding. The clinical profile of patients and the potential association with the antiarrhythmic efficacy of the procedure are mostly unexplored. Purpose To better characterize clinical profile and potential association with antiarrhythmic efficacy of patients undergoing PSGB for ES. Methods Patients undergoing PSGB for ES in our Center from 2/2021 to 2/2024 were enrolled; all the dynamic variables were evaluated in a per procedure analysis. Results 45 patients (93% male, 64 ± 10 years) received a total of 80 PSGB performed with the lateral, ultrasound (US) guided technique; most PSGB consisted of a single bolus anesthetic injection (lidocaine + ropivacaine), 26% in an additional continuous infusion, mostly with ropivacaine. All procedures except for 3 in a single patient who had previously received left cardiac sympathetic denervation, were performed on the left side. Most of the patients (60%) suffered ischemic cardiomyopathy (CMP), including 10 with an acute coronary syndrome; the rest had non-ischemic CMP; 60% had an ICD. The type of VAs was ventricular tachycardia (VTs) only in 86% of the procedures (cycle length 404 ± 143 msec), VT and VF in 10% and VF only in 3 (4%). Most PSGB (81%) were performed in the setting of impending or manifest cardiogenic shock (SCAI classification B or more), including 20% with sepsis. Cardiac US performed before (within 12 hours) each PSGB showed a severely depressed left ventricular (LV) function (mean LVEF 22 ± 10%, mean LV outflow tract velocity time integral 12 ± 4 cm), calculated at a mean heart rate of 81 ± 16 bpm. Mean LVEDV was 252 ± 104 ml, 79% had mitral regurgitation (MR) ≥2+/4+ (including 39% severe MR), 50% had ≥ moderate diastolic dysfunction, 29% had right ventricular dysfunction (mean fractional areal change 33± 7%). Most cases (75%) experienced a complete VAs suppression (sustained or treated) in the 12 hours after PSGB; only 3/80 cases required additional urgent antiarrhythmic strategies (intra-aortic ballon pump in one case, urgent pacing in another one, urgent revascularization in the last one). None of the assessed clinical or echocardiographic characteristics was significantly associated with VT cycle length or the response to PSGB. Only 1 (1%) major complication occurred (respiratory arrest), that was quickly and effectively treated with lipid emulsion. Conclusions PSGB in our Center was mostly performed in the setting of primary impending or manifest cardiogenic shock with severely impaired cardiac function, with an excellent safety profile. None of the assessed clinical or echocardiographic variables were associated with response to PSGB. Our data, despite preliminary and requiring confirmation, suggests always considering PSGB in the urgent/emergent setting independently from patients’ characteristics.

The application of supine bicycle exercise stress echocardiograph for identification of susceptibility to acute mountain sickness

Abstract Background Exposure to high altitude is likely to lead to acute mountain sickness (AMS). At present, there are no definite parameters that can accurately predict the occurrence of AMS. Objectives The purposes of this study are (1) to assess the relationship between stress echocardiographic parameters and AMS, (2) to identify the predictors of AMS at sea level by exercise stress echocardiography. Methods A total of 36 healthy adults were enrolled and underwent resting and exercise stress echocardiography on a supine bicycle at sea level. Heart rate (HR) and blood pressure (BP) were monitored during stress echocardiography. Left ventricular (LV) ejection fraction and E/e’ were calculated at rest and peak stage. Other right ventricular systolic function parameters and pulmonary artery pressure (PAP) were calculated at the same time, which included tricuspid regurgitation velocity (TRV), tricuspid annular peak systolic excursion (TAPSE), systolic PAP (sPAP), right ventricular (RV) dimension by 2D, right ventricular area at the end of diastole (RVAD), right ventricular area at the end of systolic (RVAS),RV fraction of area change (FAC), right ventricular outflow tract velocity time integral (RVOT VTI).Pulmonary vascular resistance (PVR) was calculated. All subjects ascended to 3600m within 24 hours by bus. AMS was identified by 2018 Lake Louise Questionnaire Score. Univariable and multivariable logistic regression analysis assessed independent factors associated with AMS. Results At the altitude of 3600m, 13 of 36 subjects had AMS, which defined as AMS (+) group. And the rest was AMS (-) group. There were no significant differences in HR, BP, and LV systolic and diastolic function between the two groups (P > 0.05). TRV, sPAP, and PVR were much higher at peak stage in AMS (+) group (P < 0.05). No significant differences were found in RV systolic function at rest and peak stage between the two groups. By multivariable logistic regression model, PVR and RVAD at peak stage were significantly associated with AMS occurrence (PVR-OR =1.962,95% CI: 0.689-0.973,p =0.002; RVAD-OR =1.962,95% CI: 0.638-0.967,p =0.005;). The cutoff value to predict AMS were 1.55 for PVR (AUC: 0.831) and 11.45 cm2 for RVAD (AUC: 0.802). Conclusions Supine bicycle exercise stress echocardiography is a useful and noninvasive technique to identify subjects susceptible to AMS. Subjects with higher PVR and RVAD at peak stage were associated with susceptibility to AMS.