322 Atrial morphological and functional parameters in hypertrophic cardiomyopathy: cardiovascular outcome implication

Aims The impact of atrial function measured by standard and advanced echocardiographic techniques is emerging in various clinical settings but remains poorly explored in patients with hypertrophic cardiomyopathy (HCM). Methods and results Consecutive patients with HCM referred to the heart failure outpatient clinic were prospectively enrolled. Complete clinical and echocardiographic evaluation was performed, including fully automated 2D speckle tracking analysis software (AutoStrain, TomTec). Atrial function was assessed by means of left atrial (LA) volume, LA diameter, a’-TDI, and global peak atrial longitudinal strain (PALS). The primary endpoint was a composite of cardiovascular (CV) events (cardiovascular death or hospitalization, new-onset atrial fibrillation, surgical myectomy, sustained ventricular tachycardia or ventricular fibrillation) during the follow-up. A total of 40 patients with confirmed HCM diagnoses and complete follow-up were included, mean age was 61 ± 14 years, 62% male, ejection fraction 64 ± 8%. LA was frequently enlarged (indexed LA volume 43 ± 14 ml/m2, LA diameter 39 ± 7 mm), and dysfunctional (a’-TDI 7.1 ± 2.2 cm/s, PALS 21 ± 7%). During a mean follow-up of 460 ± 300 days, seven patients had a CV event. Among LA parameters, septal a’-TDI seems to characterize patients with events the most (5.5 ± 2.1 vs. 7.5 ± 2.3, P = 0.03). This was confirmed in an age-adjusted survival model [HR: 0.62 (0.39–0.92), P = 0.03]. The spline curve in the Figure illustrates the relationship between a’-TDI and the age-adjusted probability of CV events; the association began at about 7 cm/s and increased steeply for lower values. Of note, the association between PALS and CV events was highly significant in younger patients (<70 years, P < 0.001). Conclusions According to our pilot study, a’-TDI can be considered a simple, feasible, and routinely available parameter of left atrial function, which can help to identify HCM patients at higher risk of CV events.

Plasma metabolomic profiling of hypertrophic cardiomyopathy patients before and after surgical myectomy suggests postoperative improvement in metabolic function

Background Hypertrophic cardiomyopathy (HCM) is a common inherited heart disorder complicated by left ventricle outflow tract (LVOT) obstruction, which can be treated with surgical myectomy. To date, no reliable biomarkers for LVOT obstruction exist. We hypothesized that metabolomic biomarkers for LVOT obstruction may be detectable in plasma from HCM patients. Methods We conducted metabolomic profiling on plasma samples of 18 HCM patients before and after surgical myectomy, using a commercially available metabolomics platform. Results We found that 215 metabolites were altered in the postoperative state (p-value < 0.05). 12 of these metabolites were notably significant after adjusting for multiple comparisons (q-value < 0.05), including bilirubin, PFOS, PFOA, 3,5-dichloro-2,6-dihydroxybenzoic acid, 2-hydroxylaurate, trigonelline and 6 unidentified compounds, which support improved organ metabolic function and increased lean soft tissue mass. Conclusions These findings suggest improved organ metabolic function after surgical relief of LVOT obstruction in HCM and further underscore the beneficial systemic effects of surgical myectomy.

Extended myectomy for apical hypertrophic cardiomyopathy: a case report

Background Apical hypertrophic cardiomyopathy is a variant of hypertrophic cardiomyopathy that predominantly affects the apex of the left ventricle and rarely involves the right ventricular apex or both apexes. Heart transplantation is the traditional treatment for apical hypertrophic cardiomyopathy. Although surgical myectomy approaching the apex has been available for decades, its safety and accuracy greatly depend on the surgeon’s skills and experience. Case presentation The first case involved a 63-year-old man with apical hypertrophic cardiomyopathy, wherein preoperative contrast computed tomography findings revealed apical hypertrophy and complete apical cavity obliteration. The patient underwent extended myectomy, which revealed the apex cavity filled with abnormal muscles. Using the transaortic approach, the location of the bilateral papillary muscle was confirmed, thereby providing the required orientation. The abnormal muscle mass was successfully resected, and the postoperative end-diastolic volume was extremely increased. The second case involved a 43-year-old man with an apical left ventricular aneurysm and mid-hypertrophic cardiomyopathy obstruction. The thin-walled apical aneurysm contained a large apical-basal band. Upon detecting the bilateral papillary muscle, mid-ventricular myectomy was performed from the apex. During postoperative catheterization, there was no pressure gradient between the left ventricle and aorta. Conclusions We reviewed two cases of apical hypertrophic cardiomyopathy, efficiently treated using extended apical myectomy. Although it is an uncommon procedure, the cases presented show how it can be used to successfully manage cases of apical hypertrophic cardiomyopathy. However, it is important to secure the postoperative left ventricular end-diastolic volume.

Selective Interventricular Septal Radiofrequency Ablation in Patients With Hypertrophic Obstructive Cardiomyopathy: Who Can Benefit?

Introduction: Septal mass reduction is beneficial for hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow (LVOT) gradient and symptoms, with surgical myectomy or alcohol septal ablation (ASA) currently recommended in selected patients. Radiofrequency (RF) ablation of hypertrophied septum has been published as a novel method to alleviate LVOT obstruction in small populations. This study aims to investigate factors influencing clinical outcomes of radiofrequency septum ablation.Methods and Results: In this study, 20 patients with HOCM who underwent endocardial ablation were included. Echocardiography and cardiac MRI (CMR) data was collected and analyzed pre- and (or) post- procedure. Nineteen patients underwent ablation successfully, while ablation was aborted in one patient with prior RBBB due to transient complete atrioventricular block (AVB). After 6 months of follow-up, NYHA heart functional class improved from III (2 - 3) to II (1 - 2) (p &lt; 0.001), and resting LVOT gradient was significantly reduced (87.6 ± 29.5 mmHg vs. 48.1 ± 29.7, p &lt; 0.001). LVOT gradient reduction was significantly higher in patients with limited basal septal hypertrophy (60.9 ± 8.3 vs. 27.9 ± 7.1, p = 0.01), shorter anterior mitral leaflet (56.1 ± 6.4 vs. 20.4 ± 5.0, p &lt; 0.01), and normally positioned papillary muscle (36.9 ± 7.1 vs. 75.0 ± 6.3, p &lt; 0.05).Conclusions: Endocardial septal ablation appears to be a safe and effective procedure for alleviating LVOT gradient in patients with HOCM, especially in those with limited basal septal hypertrophy, shorter anterior mitral leaflet, and normal positioned papillary muscle.

Cellular determinants of arrhythmic rysk in hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiac disease, with a prevalence of 1/500 in the general population. The most devastating consequence of HCM is sudden cardiac death (SCD) due to ventricular fibrillation, particularly common in children and young adults (age &lt;30 years). The positive correlation between the extent of late gadolinium enhancement (LGE, reflecting myocardial fibrosis) and the arrhythmic risk in HCM suggests that ventricular arrhythmias are held to originate from the fibrotic regions, by a mechanism of electrical re-entry. However, recent data suggest that enhanced cellular automaticity (i.e. early- or delayed-afterdepolarizations, EADs or DADs-), rather than macro-reentry, may be clinically relevant in promoting ventricular arrhythmias in patients. Purpose Aiming to better understand the cellular and molecular mechanisms of arrhythmogenesis in HCM and to establish a reliable arrhythmic risk stratification in patients, we performed a translational study in HCM patients who underwent surgical myectomy, by combining a clinical follow-up study with in vitro assessments of cellular arrhythmogenicity in ventricular cardiomyocytes. Methods We retrospectively studied 61 HCM patients who underwent surgical interventricular-septum myectomy to relieve refractory obstruction-related symptoms. At the time of surgery, fresh ventricular tissue was collected and used to isolate single ventricular cardiomyocytes (CMs), which were used for patch-clamp measurements to assess the occurrence of EADs and DADs. Patients were followed up for a median time of 8 years and the occurrence of non-sustained ventricular tachycardia (NSVT) or life-threatening arrhythmic events (LAE) was monitored. Moreover, data from ECG and contract cardiac magnetic-resonance studies were collected. Results EADs occurred in CMs from 36% of patients and were associated with prolonged action potential duration. DADs occurred in 24% of patients and were associated with abnormalities of CM intracellular Ca2+ handling. The occurrence of NSVT/ LAE in patients was strongly associated with the presence of DADs in cardiomyocytes but not with the presence of EADs. Patients with NSVT/LAE were more likely to show specific “pro-arrhythmic” pathological ECG-patterns. Among patients with LGE, the presence of DADs in cells behaved as a necessary pre-requisite for NSVT/LAE, as none of the patients with evidence of fibrosis who were negative for DADs had arrhythmic events. Conclusions The presence of pro-arrhythmic changes appears to be necessary for arrhythmia generation in HCM and seems to be related with specific alterations at ECG level, that might be used as clinical arrhythmia predictors in HCM patients. Fibrosis per se is not a major predictor of arrhythmias in HCM but may contribute to generate sustained arrhythmias in the presence of substantial cellular triggers (DADs). FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Horizon 2020. Grant number 777204 (silico FCM).

Outcomes in Patients With Obstructive Hypertrophic Cardiomyopathy and Concomitant Aortic Stenosis Undergoing Surgical Myectomy and Aortic Valve Replacement

Background Hypertrophic cardiomyopathy (HCM) and aortic stenosis can cause obstruction to the flow of blood out of the left ventricular outflow tract into the aorta, with obstructive HCM resulting in dynamic left ventricular outflow tract obstruction and moderate or severe aortic stenosis causing fixed obstruction caused by calcific degeneration. We sought to report the characteristics and longer‐term outcomes of patients with severe obstructive HCM who also had concomitant moderate or severe aortic stenosis requiring surgical myectomy and aortic valve replacement. Methods and Results We studied 191 consecutive patients (age 67±6 years, 52% men) who underwent myectomy and aortic valve (AV) replacement (90% bioprosthesis) at our center between June 2002 and June 2018. Clinical and echo data including left ventricular outflow tract gradient and indexed AV area were recorded. The primary outcome was death. Prevalence of hypertension (63%) and hyperlipidemia (75%) were high, with a Society of Thoracic Surgeons score of 5±4, and 70% of participants had no HCM‐related sudden death risk factors. Basal septal thickness and indexed AV area were 1.9±0.4 cm and 0.72±0.2 cm 2 /m 2 , respectively, while 100% of patients had dynamic left ventricular outflow tract gradient >50 mm Hg. At 6.5±4 years, 52 (27%) patients died (1.5% in‐hospital deaths). One‐, 2‐, and 5‐year survival in the current study sample was 94%, 91%, and 83%, respectively, similar to an age‐sex–matched general US population. On multivariate Cox survival analysis, age (hazard ratio [HR], 1.65; 95% CI, 1.24–2.18), chronic kidney disease (HR, 1.58; 95% CI, 1.21–2.32), and right ventricular systolic pressure on preoperative echocardiography (HR, 1.28; 95% CI, 1.05–1.57) were associated with longer‐term mortality, but traditional HCM risk factors did not. Conclusions In symptomatic patients with severely obstructive HCM and moderate or severe aortic stenosis undergoing a combined surgical myectomy and AV replacement at our center, the observed postoperative mortality was significantly lower than the expected mortality, and the longer‐term survival was similar to a normal age‐sex–matched US population.

CMR derived ventricular arterial coupling in hypertrophic cardiomyopathy

Funding Acknowledgements Type of funding sources: None. Introduction Ventriculoarterial coupling (VAC) is an important surrogate measurement of global cardiovascular efficiency. However, up till recently, this measurement has been rarely used in clinical practice. This could be due to its invasive nature, and the relatively complex methods required for acquisition and interpretation. We here describe a noninvasive method of measuring VA coupling using cardiac magnetic resonance (CMR) in a cohort of hypertrophic cardiomyopathy (HCM). Methods Cardiac MRI was performed in 61 patients with hypertrophic obstructive cardiomyopathy (HOCM) before and after undergoing extended surgical myectomy. Cardiac MRIs from 15 patients with non-obstructive HCM were also included for comparison. Hypertensive patients were excluded from this study. Vitals signs were recorded during each MRI study. Arterial end-systolic pressure (AESP) was determined non-invasively as previously described (0.9x brachial blood pressure). Left ventricular end-systolic pressure (LVESP) was calculated by adding the echo-derived peak systolic gradient across the left ventricular outflow tract to the arterial end-systolic pressure. Indexed stroke volume (SVI) in the ascending aorta as well as indexed end systolic volume (ESVI) were calculated from CMR. Indexed arterial (Ea) and ventricular (Ev) elastance were calculated as AESP/SVI and LVESP/ESVI. VA coupling was then calculated as Ea/Ev. Results Compared to the baseline measurements, VAC increased significantly post myectomy (mean VAC pre-myectomy and post-myectomy 0.38 vs. versus 0.62 respectively, p= 0.00001). VAC in non-obstructive HCM patients (mean = 0.64) was statistically similar to that in post-myectomy (p = 0.82) and statistically different from pre-myectomy (p = 0.00016). The mean of LVOTO gradients post- and pre-myectomy were significantly different (p = 0.00001). Significant correlation of the delta-VAC with the delta gradient in the LVOTO was found (r= 0.35, p = 0.005). Conclusion Non-invasive assessment of VA coupling using CMR is feasible and could be a useful tool in the evaluation of patients with various cardiovascular disorders. Further studies with larger numbers of patients are required to establish the utility of this method in clinical practice.