Ventricular Outflow Tract Obstruction Research Articles

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.

Residual mitral leaflet length independently indicates left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Abstract Background Due to its dynamic character, the diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive exercise testing. Mitral valve alterations represent structural parameters that are not affected by load or contractility and influence left ventricular outflow tract (LVOT) gradients. The residual portion of the mitral valve extending past its coaptation (RML) has been postulated as a necessity to exhibit LVOTO. Purpose This study aims to assess the impact of RML length on the likelihood of LVOTO in HCM patients. Methods This is a cross-sectional, multi-center, registry-based analysis conducted at two HCM referral centers. The study included HCM patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses. LVOTO was defined as resting or dynamic peak LVOT gradients ≥30 mmHg. Results Among 270 HCM patients studied (43% women, mean age 58±14 years), 131 patients (49%) exhibited LVOTO, with 76 (28%) having undergone septal reduction therapy (SRT). Patients with obstructive HCM exhibited a more pronounced end-diastolic interventricular septum (IVSd) thickness (2.2±0.4 vs. 1.8±0.5 cm; p<0.001) and higher left ventricular ejection fraction (LVEF) (65±9 vs. 62±10%; p=0.009) compared to those without LVOTO (nHCM). Obstructive HCM patients demonstrated longer anterior (29±4 vs. 26±4 mm; p<0.001), posterior (23±4 vs. 20±4 mm; p<0.001), and residual mitral leaflets (11±3 vs. 7±3 mm; p<0.001) than nHCM patients. Multivariable logistic regression analysis adjusting for age, IVSd thickness, LVEF, anterior, and posterior mitral leaflet length identified RML length as an independent predictor of LVOTO [OR=1.47 (95% CI 1.30-1.66); p<0.001]. The area under the receiver-operating characteristic curve for RML length in identifying LVOTO was 0.82 (95% CI 0.77-0.87). RML length ≥9 mm demonstrated 73% sensitivity and 77% specificity in identifying obstructive HCM patients. Notably, these results remained statistically significant in sensitivity analyses selectively performed in HCM patients who had previously undergone SRT as well as in those who were SRT-naïve, respectively. Conclusions This study indicates RML length as an independent predictor of LVOTO in HCM patients. Moreover, RML length demonstrated high diagnostic accuracy in identifying LVOTO among HCM patients. Prospective studies are warranted to assess the added value of RML length in the diagnostic work-up of HCM patients.Figure:Diagnostic Accuracy of RML

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.

Phenotype progression in pediatric RASopathy-associated hypertrophic cardiomyopathy

Abstract Background RASopathy syndromes represent the second most common cause of hypertrophic cardiomyopathy (HCM) in children. RASopathy associated HCM (Ras-HCM) has been shown to differ both in cardiac phenotype and long-term outcomes from sarcomeric HCM. However, there is a lack of knowledge from large cohort studies of how the cardiac phenotype of Ras-HCM changes over time. Aim To describe cardiac phenotype changes over time in children with Ras-HCM Methods Retrospective data from 148 patients diagnosed with Ras-HCM aged <18 years with ³2 follow-up visits were included. Clinical and echocardiographic data were collected at baseline assessment, 1, 2, and 5 years of follow up. Separate analyses were performed for patients who survived, versus patients who died or had a heart transplant (censoring events). Results One-hundred-and-two (68.9%) patients with Noonan syndrome, 25 (16.9%) with Noonan-syndrome with multiple lentigines, 10 (6.8%) with Costello syndrome, 9 (6.1%) with cardio-facio-cutaneous syndrome and 2 (1.4%) patients with Noonan-like syndrome with a median age of diagnosis 0.16 years (0.01-0.89) were seen at a median baseline age of 1.41 years (0.37-5.71) and followed up for a median of 12.1 years (4.8-17.4). During follow up, 18 patients (12.2%) died at a median age of 1.8 years (0.5-8.7) and 17 (12.5%) had a left ventricular myectomy, at a median age of 7.0 years (3.1-12.7). At baseline evaluation, patients who died compared to those who survived had a lower median age [0.4 years (0.1-0.8) versus 2.3 years (0.5-7.6), p<0.001], a higher proportion of them had a NYHA class>I (54.5% vs 15.1%, p<0.001), a higher maximal left ventricular wall thickness (MLVWT) z-score [13.4 (7.5) vs 9.6 (6.2), p=0.04], a higher proportion of left ventricular outflow tract obstruction (LVOTO) [64.7% vs 43.8%, p=0.087] and a higher proportion of biventricular hypertrophy [75% vs 49.2%, p=0.045]. For survivors, the MLVWT z-score improved over follow up [+9.6(6.2) at baseline vs. +7.9(5.5) at 5 years, p=0.072], and the proportion of patients with LVOTO (43.8% at baseline vs. 27.9% at 5 years, p=0.019) and biventricular hypertrophy (49.2% at baseline vs. 35.5% at 5 years, p=0.012) decreased over follow up. Conclusion While at baseline evaluation Ras-HCM has a high burden of symptoms, biventricular hypertrophy and LVOTO for patients who die or have a heart transplant, we have demonstrated that for survivors, over follow up, the phenotype becomes milder.Table 1

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.

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.

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.

Effect of alcohol septal ablation on exercise hemodynamics, symptoms and quality of life in patients with obstructive hypertrophic cardiomyopathy

Abstract Background The comprehensive impact of septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy (HCM), including exercise hemodynamics and quality of life (QoL), remains poorly understood. Purpose The aim of this study was to evaluate the effect of alcohol septal ablation (ASA) in mitigating left ventricular outflow tract (LVOT) obstruction, reducing filling pressures during exercise, and the effect on QoL in patients with obstructive HCM. Methods This prospective study enrolled 24 patients with obstructive HCM referred for ASA. Evaluations included right-heart catheterization and echocardiography performed at rest and during exercise, before and approximately six months post-ASA. The primary outcome was the difference in filling pressures assessed by pulmonary capillary wedge pressure (PCWP) at 75 Watt (W). Secondary outcome assessed LVOT gradients, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and exercise capacity. Results ASA significantly reduced PCWP at 75 W (24 ± 10 mmHg vs 33 ± 9 mmHg; P = 0.0001) (Figure 1), decreased LVOT gradients at rest (49 mmHg (24-90) vs 17 mmHg (14-27); P=0.002), at peak exercise (45 mmHg (29-90) vs 32 mmHg (21-61); P = 0.02), and post-exercise (96 mmHg (34-161) vs 28 mmHg (21-62); P=0.004). The KCCQ-OSS score was also significantly reduced (75.6 ± 18.8 vs 64.7 ± 16; P = 0.006), without affecting peak oxygen consumption (19.9 ± 4.8 ml/kg/min vs 18.7 ± 3.6 ml/kg/min; P = 0.26). The improvement in the KCCQ score was confirmed by changes in NYHA functional class. Before ASA treatment, 54% of patients were in NYHA functional class III compared to 13% after ASA (P < 0.0005). Conclusion ASA substantially reduces exercise-induced filling pressures, reduces LVOT obstruction, and improves symptoms and QoL in obstructive HCM, without impacting maximal exercise capacity.

Exploring the effects of mavacamten through hemodynamic force analysis in patients with obstructive hypertrophic cardiomyopathy

Abstract Introduction Mavacamten is a first-in-class allosteric myosin inhibitor effective in relieving left ventricular (LV) outflow tract obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). To date, however, its effect on cardiac mechanics is still unclear. Hemodynamic force (HDF) analysis represents the fluid dynamics correlate of deformation imaging, showing a greater sensitivity in detecting early mechanical abnormalities or response to treatment [1]. Purpose To explore the in vivo effect of mavacamten on cardiac mechanics in patients with HCM after a 3 year-treatment, using HDF analysis. Methods LV HDF analysis was performed in 6 patients with oHCM (representing a cohort of the MAVA-LTE study) at baseline and after 3 years of treatment. Apical 4-, 2-, and 3-chamber echocardiographic views were analysed using a dedicated and sofisticated software. Base-apex forces (where positive deflections represent a force directed from the apex to the base of LV, whilst negative ones are directed toward the LV apex) were assessed in terms of timing indexed to cardiac cycle duration. HDF curves from the 6 patients treated with macavamten were compared to those obtained from oHCM patients (n=20), non-obstructive HCM (noHCM) patients (n=20), and healthy controls (n=22). Results Figure 1 shows a different pattern of transition between diastole and systole in HCM patients compared to controls. Specifically, HCM patients exhibited an earlier onset of the systolic phase, expressed as a fusion of late diastolic deceleration and systolic thrust. This was numerically represented as a decrease in diastolic-systolic transition time, which is 0.22 [0.20-0.24] for oHCM, 0.23 [0.21-0.25] for noHCM and 0.26 [0.26-0.30] for controls (p ≤0.001 for control vs oHCM, p ≤0.01 for control vs noHCM). Additionally, HCM patients showed an increased rate of force generation. The time to systolic peak (i.e., time interval from the onset of systole to the maximum force) was reduced in HCM patients compared to controls, and was shorter in oHCM than in noHCM patients (0.13 [0.11-0.15] vs 0.16 [0.14-0.17], p ≤0.01), thus reflecting an increased clinotropism in HCM. After 3 years of mavacamten treatment, the diastolic-systolic transition time and the time to systolic peak returned to a level similar to that of healthy controls (0.30 [0.27-0.30] in mavacamten group vs 0.26 [0.26-0.30], p >0.05, and 0.21 [0.20-0.22] vs 0.19[0.17-0.20], p=0.04, respectively) (Figure 2). Conclusion HDF analysis reveals that mavacamten affects the duration of transition from diastole to systole and prolongs time from the onset to the peak in systole. These findings may explain the removal of the mechanical coupling substrate responsible for the systolic anterior movement of mitralic leaflets and the subsequent resolution of LV outflow tract obstruction by mavacamten.Distribution of time parameters

Intra, short and long-term results of mitral VIV for the degenerated surgical mitral prosthesis from italian VIV registry (MIVIV registry)

Abstract Background/Introduction Reoperation of failed bioprosthetic mitral valves is associated with significant morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) replacement was explored early in the development of THVs with transseptal/transfemoral (TS/TF) and transapical (TA) approaches. Purpose This is the first Italian Registry on mitral VIV and it was designed to explore contemporary MViV outcomes with all types of balloon expandable valves. The present study out of the registry aims to asses the >10 years follow-up outcomes in terms of mortality, gender diversity, and perioperative result. Methods Participating centers used standardized definitions to collect clinical information, including patient demographic characteristics, comorbidities, functional status, quality of life indexes, procedural details, and patient outcomes from consecutive MViV cases. Cohort of 265 patients was available for the primary analysis and follow-up too.The patients were grouped by 11 hospitals in Italy performing VIV for degenerated biological mitral prostheses. Results A total of 265 pts underwent mitral VIV due to bioprosthesis degeneration between January 2010 and January 2023. They have been subdivided by transfemoral (TF) with 117 (44%) pts and transapical (TA) with 148 (55,8%) pts. Most of the patients were of female sex (59,2%) and EuroScore II for surgical re-operation was 16.1%. Mixed disease (48%) was more common than mitral regurgitation (29%) and stenosis (22%). 69,8% of the total cohort was in class NYHA III and the mean LVEF was 54%.Otherwise, there were no significant demographic differences between patients undergoing TS and TA. In TF there was more severe PVL (5%)(p-value: 0,001) and much more cases of severe grade of stenosis (54,7%) and regurgitation (57%)(p-value< 0,0001). Considering intraoperative outcomes, technical success has been established in around 97,7% of the total cohort without difference btw groups. Only 3,3% died during hospitalization without difference between groups (P-value=0,735). LVOT obstruction has been seen in 3,4% in the case of TA and 0 for TF. Only 1,5% of the total cohort underwent surgical conversion as well as embolization in only 1,1%. Overall survival from the total cohort was 91,3% at >10 years, Figure 1. Concerning the freedom from cardiac death (CV death) was 96,6% in the total cohort at 13 years. Concerning the difference between access, the general survival is established at 97,4% in TF while 86,3% in TA (p-value =0,050)(Figure 2). Freedom from CV death was 99,1% in TF and 94,5 in TA (p-value=0,209). In gender analysis differentiation, the general survival in females was 98,5% in TF and 85,6% in TA at 13 years (p-value=0,056). Conclusion(s) Transcatheter MViV using a balloon-expandable valve is associated with high technical success, a low complication rate, and a solid long-term benefit in terms of survival. Transseptal access was associated with lower mortality compared with TA access.Figure 1Figure 2

Changes in mental health and illness perception in patients with hypertrophic cardiomyopathy referred to hybrid cardiac telerehabilitation in comparison to usual care - a randomised-control trial

Abstract Purpose Hypertrophic cardiomyopathy (HCM) is a complex cardiac disorder, that influences patients' physical capacity and quality of life, as well as the risk of sudden cardiac death (SCD). Patients with HCM often experience emotional distress due to the uncertainty of their condition and have a threatening illness perception (the way individuals make sense of their illness, which can have a significant impact on adherence to treatment). Current studies suggest that some HCM patients could benefit from hybrid cardiac telerehabilitation (HCTR) in terms of somatic and psychological status. This study is part of a research project investigating the safety and effectiveness of hybrid cardiac telerehabilitation for HCM patients. The specific focus of this part is to evaluate the changes in mental health status and illness perception of HCM patients who have been referred for cardiac telerehabilitation compared to those receiving usual care. Methods An RCT study was conducted, with the inclusion criteria for the study of being above 18 y.o., HCM without LVOT obstruction, NYHA Class II or III, LVEF ≥ 50%, and having CIED. The study involved telerehabilitation (HCTR) and control (CG) groups. Both groups were completing questionnaires assessing illness perception (Brief IPQ) and overall psychosocial distress (GHQ-28) with its 4 domains: somatic symptoms, anxiety, social impairment, and depression. Psychological assessment was performed at the beginning and at the end of telerehabilitation/outpatient care, and at 3, 6 and 12 months after the end of care (T1/T2/T3/T4/T5). Results There was a significant improvement in the overall distress level in the HCTR group (p=0.003) but not in the CG (p=0.559). It remained significant in the HCTR group for the T2 (p<0.001), T3 (p=0.008), and T4 (p<0.001). The positive change was observed in somatic symptoms only in the HCTR group: for T2 (p=0.025) and T3 (p=0.032) compared to the T1. The gradual decrease in anxiety level was observed in the HCTR group, but not in the CG, with a significant difference for T4 (p=0.013) compared to T1. Although there was an improvement in social impairment in both groups (p=0.049 for the CG, and p=0<0.001 for the HCTR group), only in the HCTR group it held a stable pattern after the intervention (p<0.001 for T2; p=0.013 for T3; p=0.032 for T4). There were no changes in the level of depressive symptoms in either of the compared groups. There were also no significant differences in the illness perception (p=0.200 for the HCTR group and p=0.090 for the CG), although the HCTR group showed short-term improvement after three months of HCTR (T2) (p=0.032). Conclusions There are significant benefits of hybrid cardiac telerehabilitation for mental health, level of distress, and illness perception in HCM patients. It is worth noticing that this improvement is short-term, and prolonged effects might require providing additional support during extended care.overall distress in HCTR vs CGsubscales of GHQ_28 in HCTR vs CG

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.

One-year outcomes of transcatheter mitral valve replacement in patients with severe mitral regurgitation

Abstract Background Mitral valve regurgitation (MR) is a prevalent valvular heart disease, and a subset of patients face challenges in undergoing surgical treatment. Transcatheter mitral valve replacement (TMVR) has emerged as a viable option for selected patients with severe MR deemed unsuitable for traditional valve surgery. Purpose This study aims to evaluate the feasibility, safety, durability, and clinical outcomes of a novel transapical mitral valve system (MitraFix valve) in treating moderate to severe MR patients. Methods The early feasibility study of the MitraFix TMVR transapical system is a multicenter, prospective, nonrandomized study. All patients underwent evaluation by a multidisciplinary heart team and were deemed suitable for mitral valve intervention. Clinical events were adjudicated by an independent clinical events committee. Results From June 2021 to July 2022, 10 patients (mean age: 71.2 ± 7.4 years, 40% male) were enrolled. The mean Society of Thoracic Surgeons(STS) predicted risk of mortality was 7.5 ± 2.7%. All implants were successful, with a mean operational time of 45.2 ± 25.9 min. One patient was converted to open cardiac surgery after successfully implanting the valve due to persistent apical bleeding. At 1-year follow-up, all-cause mortality was 20%, with a cardiovascular mortality at 10.0%. Among survival patients, 87.5% of surviving patients had MR ≤1+ and 75% patients were in NYHA functional class I or II at 1 year. The overall KCCQ score significantly increased from 55.8 (42.9, 72.9) points at baseline to 77.5 (73.7, 88.6) points at 1-year follow up (P = 0.012). Left ventricular ejection fraction showed no significant change from basline (51.5%) to 1 year (50.0%) (P=0.799). No evidence of mitral stenosis or left ventricular outflow tract (LVOT) obstruction was observed. Conclusions The MitraFix TMVR transapical system demonstrated excellent valve function, low mortality, sustained MR elimination and clinical improvement up to one year in this study. Further studies, encompassing a larger cohort of patients and an extended follow-up duration, are needed to confirm these findings.Change in MR and NYHA functional classChange in Quality-of-Life Assessment

Functional capacity by cardiopulmonary exercise testing is not related to health status in obstructive hypertrophic cardiomyopathy

Abstract Background In obstructive hypertrophic cardiomyopathy (HCM), the primary goal of therapy is to improve patient quality of life by decreasing symptom burden. Increasingly, cardiopulmonary exercise testing (CPET), with peak oxygen consumption (pVO2) and ventilator efficacy (VE/VCO2), is used to assess efficacy of novel therapies in clinical studies and selectively in clinical practice to determine treatments. However, the relationship of CPET variables to symptom burden in HCM is not well established. Therefore, we examined the relationship between CPET variables and health status measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional classification in a cohort of obstructive HCM patients. Methods Consecutive patients with HCM and resting left ventricular outflow tract (LVOT) obstruction (≥50 mmHg) underwent CPET between October 2022 to January 2024. Patients with a peak RER <1.0 were excluded (n=4). To investigate distribution of patient reported health status (KCCQ) and NYHA functional classification, patients were stratified into groups for pVO2 (<14, 14-20, and >20 mL/kg/min) to reflect moderate to severe, mild to moderate, and little to no functional limitation, respectively. Results Of 58 patients, clinical evaluation was at 59 ± 13 years of age, 55% male, with LVOT gradient of 83 ± 28 mmHg at rest with 84% NYHA class II or III and 76% with KCCQ overall summary (OS) <75. Both pVO2 and VE/VCO2 had significant but weak correlation with NYHA class and KCCQ scores (Table 1), with the strongest correlation observed with pVO2 and KCCQ-OS (R2= 0.13, p=0.004). In contrast, % predicted pVO2 was not significantly correlated with NYHA or KCCQ. Notably, despite 14 patients being classified as having little to no limitations by pVO2, 29% of these patients had mild to moderate disability and 29% had moderate to severe disability by KCCQ-OS (Figure 1). Conclusion In patients with symptomatic obstructive HCM, objective measures of exercise performance, including pVO2 and VE/VCO2, correlate poorly with measurements of health status. These data suggest that CPET results should not be considered a surrogate marker of heart failure symptom burden in obstructive HCM.

Different microRNA expression in the right ventricular outflow tract myocardium of tetralogy of Fallot

Abstract Background When repairing tetralogy of Fallot (TOF), there are two surgical options according to the size of the pulmonary valve: transannular patch repair and valve-preserving repair. Since the development of the pulmonary valve depends on the degree of obstruction of the right ventricular outflow tract (RVOT), molecular profiles of the RVOT muscles may be associated with the surgical decision. As a recent study shows altered microRNA expression of the right ventricular myocardium even in TOF patients, microRNA expression of the RVOT infundibular muscle may be different between the two procedures. Purpose To evaluate differences in microRNA expression levels of RVOT infundibular muscles between the transannular patch repair and valve-preserving repair groups. Methods Surgically resected infundibular muscles from TOF patients are frozen in liquid nitrogen and stored in our hospital biobank. Nine samples collected between August 2020 and July 2022 were used in this study. Five patients underwent a valve-preserving repair and the others underwent a transannular patch repair. Six patients were female and mean age at operation was 453 ± 240 days. These samples were homogenized and total RNA including microRNAs were extracted. MicroRNA expression levels were measured using a microRNA array capable of detecting over 2000 microRNAs simultaneously. Results 1171 microRNAs were detected in all nine samples. The expression levels of 22 microRNAs were significantly different between the transannular patch repair group and the valve-preserving repair group (P<0.05). The expression levels of 19 microRNAs were significantly higher in the transannular patch repair group and the others were significantly higher in the valve-preserving repair group. More than 2-fold changes were observed in 2 microRNAs between the transannular patch repair and valve-preserving repair groups. Conclusion MicroRNA expression of RVOT infundibular muscle differs between the transannular patch repair and valve-preserving repair groups. Therefore, microRNA analysis will be useful to evaluate the pathophysiology of TOF. In addition, microRNAs may become a useful biomarker for surgical decision making in TOF.

Trans-femoral transcatheter intramyocardial septal radiofrequency ablation: a novel therapeutic approach for obstructive hypertrophic cardiomyopathy

Abstract Background Septal reduction techniques play a pivotal role in mitigating morbidity and mortality among patients with obstructive hypertrophic cardiomyopathy (oHCM). While trans-apical intramyocardial septal radiofrequency ablation (PIMSRA or LIWEN procedure) has shown promise in reducing left ventricular outflow tract (LVOT) gradients and improving symptoms in oHCM patients, it is associated with complications such as cardiac tamponade and atrioventricular block. Objective This study introduces a novel approach for transcatheter radiofrequency ablation of hypertrophic septum via femoral access, utilizing the DragonFire Transcatheter Myocardial Puncture and Radiofrequency Ablation System. We aim to evaluate its safety and medium-term outcomes in patients with oHCM. Methods A prospective, single-center, single-arm study of tf-PIMSRA was conducted in patients with drug-refractory oHCM. Ten patients were enrolled and underwent the procedure under the guidance of transesophageal echocardiography. The primary outcome was 30-day major adverse clinical events, with secondary outcomes including 90-day improvements in outflow obstruction and quality of life. Results All patients, with an average age of 57±10 years, including 4 males, underwent the procedure successfully without any complications, including major adverse clinical events or conduction abnormalities. The average duration of the procedure was 125.2±34.6 minutes, with an average ablation time of 38.69±18.29 minutes and ablation energy of 3.60±1.49KJ. At 90-day follow-up, significant reductions were observed in peak LVOT gradients (resting gradient: from 82.00 [56.00] mmHg to 14.00 [6.25] mmHg; p < 0.001; provoked gradient: from 102.00 [76.25] mmHg to 33.00 [16.50] mmHg; p = 0.002), and interventricular septum thickness (from 22.00 [19.00] mm to 17.00 [15.00] mm; p = 0.002). These improvements were associated with enhancements in NYHA functional classification (from 3.00 [2.75] to 1.00 [1.00]; p < 0.0001), Kansas City Cardiomyopathy Questionnaire scores (from 59.00 [44.50] to 80.00 [77.25]; p < 0.02), 6-minute walk distance (from 441 [400] m to 480 [465] m; p < 0.01), and pro B-type natriuretic peptide levels (from 1738.00 [1113.25] pg/ml to 252.00 [200.00] pg/ml; p = 0.002). All patients achieved New York Heart Association functional class I or II at follow-up. Conclusions Transfemoral PIMSRA appears to be a safe and effective procedure for relieving LVOT obstruction and symptoms in patients with drug-refractory oHCM. These findings support further investigation through randomized clinical trials comparing it with established septal reduction therapies.Patient-Level Outcomes for the trans-fem

Transcatheter mitral replacement: what are the outcomes of un-eligible patients compared to treated?

Abstract Background/Introduction Transcatheter mitral valve replacement (TMVR) is emerging in recent years as a promising tool to treat mitral regurgitation, however its applicability in the real world remains limited. Purpose The aim of the study is to assess the real-world screening success rate of TMVR in native anatomy and the 1-year outcomes of both accepted and refused patients as well as clinical results. Methods Retrospective analysis was performed on all patients screened for TMVR at our Valve Center, eligible for 1-year follow-up. In-hospital data of all patients admitted to our Department are prospectively collected. Follow-up was done through outpatient visits and/or telephone calls. Results Out of 3400 patients referred to mitral treatment at our department between January 2016-January 2022, 92 were submitted to screening for TMVR. Among these, 48 patients (49%) were accepted and treated with TMVR while 44 (44.8%) were refused (RG). The main reasons for rejection were anatomy unfeasibility in 25 patients (59%) and frailty in 5(11%). Main reasons for anatomy unfeasibility were risk LVOT obstruction (n=15; 60%), annular dimension (n=8; 33%) and ventricular dimension (n=2; 8,3%).Major baseline characteristics between groups were similar including age (85 vs 84), STS (12 vs 13), ejection fraction and LVEDD. However, refused patients had higher filtration rate than TMVR (80 vs 45 ml/min respectively (p=0.001)).All patients accepted were treated with TMVR: 7 patients received Tiara and 24 Tendyne. Procedure success in the TMVR group was 96% (46/48). Patients refused from TMVR were treated with Mitraclip in 5(11%) cases, 37(84%) were left in medical therapy and 2 (4,5%) underwent surgery. 1-year overall survival 65.2±51.3 vs 54.8±36.5 in TMVR and refused group respectively (p=0.002)(Figure 1). 6 deaths (2 cardiac, 33%) occurred in the TMVR compared to 37 (32 cardiac, 86%) in the refused group. Freedom from Cardiac death was 98±19% TMVR vs 75±65% (p<0.001)(Figure 2). NYHA class improved in 98% of cases in TMVR group but worsened in 80% in refused group, (p<0.001). TMVR screening failure is associated with increased cardiac death (HR 12 [1,51;95], p<0,019) and death for any causes (HR 17,5 [6,02;51], p<0,001). Conclusion(s) In the present experience, approximately 50% of patients screened for TMVR were accepted. The most frequent reasons for screening failure were anatomical issues. With a baseline similar clinical profile, treatment with TMVR provided significant 1-year survival and symptoms improvement compared to those of patients refused, whose prognosis is indeed remarkably poor. These data underline the importance of proper patient selection for TMVR to achieve good outcomes but also the need for technological improvement of devices to expand the proportion of patients who can be treated. Given the small numbers currently available, more data are needed to confirm the present findings, which must be considered hypothesis-generating.Figure 1Figure 2

A successful surgical repair for supravalvular aortic stenosis with a bicuspid valve and malpositioned coronary orifices by partial Brom’s technique: a case report

BackgroundSupravalvular aortic stenosis (SVAS) is a relatively rare form of left ventricular outflow tract obstruction, often accompanied by other cardiac conditions. However, a standard surgical reparative technique has not been established and repairing SVAS remains challenging.Case presentationWe repaired SVAS of a 3-year-old boy accompanied by a bicuspid aortic valve and malpositioned coronary orifices by partial Brom’s technique with two glutaraldehyde-treated autologous pericardial patches, using recent advanced preoperative information, including geometric and effective heights. Echocardiography after the surgery revealed release of SVAS without aortic regurgitation.ConclusionsIn repair for SVAS, it is important not only to release stenosis but also to make a functional aortic valve, using recent advanced preoperative information. In the case of children, repairing the aortic valve by only using autologous tissue having growth potential, is also important.

Clinical features and surgical outcomes of membranous subaortic stenosis in three siblings: a case series and literature review

Introduction: Subvalvular aortic stenosis (SAS) is a rare heart condition that can cause LVOT obstruction and lead to serious complications. While surgery is the main treatment, recurrence is a concern. This case series highlights the challenges in managing SAS in young patients. Case Series: Three young brothers presented with symptoms of shortness of breath and chest tightness. All were diagnosed with membranous SAS through echocardiography and Doppler ultrasound. Surgical intervention was performed to remove the obstruction, but all three patients experienced recurrence within two years. Discussion: This case series of three brothers suggests a genetic predisposition. Symptoms included exertional dyspnea and chest tightness, diagnosed via echocardiography. Surgical intervention is the primary treatment, but its timing is debated due to recurrence risks and complications. Conclusions: This case series suggests a possible genetic predisposition to SAS. Despite successful initial surgery, the high recurrence rate highlights the need for improved management strategies and long-term follow-up. Further research is crucial to understand the causes of recurrence and optimize treatment for children with SAS.

Transcatheter Myotomy for Hypertrophic Obstructive Cardiomyopathy.

To describe the emerging role of transcatheter septal myotomy in the treatment of hypertrophic obstructive cardiomyopathy. Transcatheter septal myotomy was developed to address risk of LVOT obstruction during TMVR, however it has been performed in patients with LVOT obstruction related to hypertrophic cardiomyopathy, in whom it improves symptoms, reduces LVOT gradients, and is associated with low incidence of procedural complications. Transcatheter myotomy is a novel approach to address LVOT obstruction related to hypertrophic cardiomyopathy in patients who are not favorable surgical candidates. The risk of conduction abnormalities with transcatheter septal myotomy appears low. Research is needed to define optimal patient selection and long-term outcomes.