Non-invasive estimation of left ventricular systolic peak pressure: a prerequisite to calculate myocardial work in hypertrophic obstructive cardiomyopathy.

AIMS: Myocardial work (MyW) is an echocardiographically derived parameter to estimate myocardial performance. The calculation of MyW utilizes pressure strain loops from global longitudinal strain and brachial blood pressure (BP) as a surrogate of left ventricular systolic pressure (LVSP). Since LVSP cannot be equated with BP in hypertrophic obstructive cardiomyopathy (HOCM), we explored whether LVSP can be derived non-invasively by combining Doppler gradients and BP. METHODS AND RESULTS: We studied 20 consecutive patients (8 women, 12 men; mean age 57.0 ± 13.9 years; NYHA 2.1 ± 0.8; maximal septal thickness 24.7 ± 6.3 mm) with indication for first alcohol septal ablation. All measurements were performed simultaneously in the catheterization laboratory (CathLab)-invasively: ascending aortic and LV pressures; non-invasively: BP, maximal (CWmax) and mean (CWmean) Doppler gradients.LVSP was 188.9 ± 38.5 mmHg. Mean gradients of both methods were comparable (CathLab 34.3 ± 13.4 mmHg vs. CW 31.0 ± 13.7 mmHg). Maximal gradient was higher in echocardiography (64.5 ± 28.8 mmHg) compared with CathLab (54.8 ± 24.0 mmHg; P < 0.05). Adding BP (143.1 ± 20.6 mmHg) to CWmax resulted in higher (207.7 ± 38.0 mmHg; P < 0.001), whereas adding BP to CWmean in lower (174.1 ± 26.1 mmHg; P < 0.01) derived LVSP compared with measured LVSP. However, adding BP to averaged CWmax and CWmean resulted in comparable results for measured and derived LVSP (190.9 ± 31.6 mmHg) yielding a favourable correlation (r = 0.87, P < 0.001) and a good level of agreement in the Bland-Altman plot. CONCLUSION: Non-invasive estimation of LVSP in HOCM is feasible by combining conventional BP and averaged CWmean and CWmax gradients. Hereby, a more reliable estimation of MyW in HOCM may be feasible.

Low-grade systemic inflammation and left ventricular dysfunction in hypertensive compared to non-hypertensive hypertrophic cardiomyopathy.

BACKGROUND: Arterial hypertension (HTN) is associated with excess mortality in hypertrophic cardiomyopathy (HCM), but underlying mechanisms are largely elusive. The objective of this study was to investigate the association between HTN and markers of left ventricular (LV) dysfunction and low-grade systemic inflammation in a HCM cohort. METHODS: This was a single-center cross-sectional case-control study comparing echocardiographic and plasma-derived indices of LV dysfunction and low-grade systemic inflammation between 30 adult patients with HCM and HTN (HTN+) and 30 sex- and age-matched HCM patients without HTN (HTN-). Echocardiographic measures were assessed using post-processing analyses by blinded investigators. RESULTS: Mean age of the study population was 55.1 ± 10.4 years, 30% were women. Echocardiographic measures of systolic and diastolic dysfunction, including speckle-tracking derived parameters, did not differ between HTN+ and HTN-. Moreover, levels of N-terminal pro B-type natriuretic peptide were balanced between cases and controls. Compared with HTN-, HTN+ patients exhibited a higher white blood cell count [8.1 ± 1.8 109/l vs. 6.4 ± 1.6 109/l; p < 0.001] as well as higher plasma levels of interleukin-6 [2.8 pg/ml (2.0, 5.4) vs. 2.1 pg/ml (1.5, 3.4); p = 0.008] and high-sensitivity C-reactive protein [2.6 mg/l (1.4, 6.5) vs. 1.1 mg/l (0.9, 2.4); p = 0.004]. CONCLUSION: This study demonstrates that HTN is associated with indices of low-grade systemic inflammation among HCM patients. Moreover, this analysis indicates that the adverse impact of HTN in HCM patients is a consequence of systemic effects rather than alterations of cardiac function, as measures of LV systolic and diastolic dysfunction did not differ between HTN+ and HTN-.

Outcomes of Alcohol Septal Ablation in Patients With Severe Left Ventricular Outflow Tract Obstruction: A Propensity Score Matching Analysis.

BACKGROUND: The current ACC/AHA guidelines on hypertrophic cardiomyopathy (HCM) caution that alcohol septal ablation (ASA) might be less effective in patients with left ventricular outflow tract obstruction (LVOTO) ≥ 100 mm Hg. METHODS: We used a multinational registry to evaluate the outcome of ASA patients according to baseline LVOTO. RESULTS: A total of 1346 ASA patients were enrolled and followed for 5.8 ± 4.7 years (7764 patient-years). The patients with baseline LVOTO ≥ 100 mm Hg were significantly older (61 ± 14 years vs 57 ± 13 years; P < 0.01), more often women (60% vs 45%; P < 0.01), and had a more pronounced HCM phenotype than those with baseline LVOTO < 100 mm Hg. There were no significant differences in the occurrences of 30-day major cardiovascular adverse events in the 2 groups. After propensity score matching (2 groups, 257 pairs of patients), the long-term survival was similar in both groups (P = 0.10), the relative reduction of LVOTO was higher in the group with baseline LVOTO ≥ 100 mm Hg (82 ± 21% vs 73 ± 26%; P < 0.01), but the residual resting LVOTO remained higher in this group (23 ± 29 mm Hg vs 13 ± 13 mm Hg; P < 0.01). Dyspnoea (NYHA functional class) at the most recent clinical check-up was similar in the 2 groups (1.7 ± 0.7 vs 1.7 ± 0.7; P = 0.85), and patients with baseline LVOTO ≥ 100 mm Hg underwent more reinterventions (P = 0.02). CONCLUSIONS: After propensity matching, ASA patients with baseline LVOTO ≥ 100 mm Hg had similar survival and dyspnoea as patients with baseline LVOTO < 100 mm Hg, but their residual LVOTO and risk of repeated procedures were higher.

Spatial relationship between mitral valve and ventricular septum assessed by resting echocardiography to diagnose left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

AIMS: Echocardiographic diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive provocative manoeuvers. We investigated, whether echocardiography-derived parameters obtained at rest can aid to determine the presence of LVOTO in persons with HCM. METHODS AND RESULTS: Consecutive patients with HCM admitted to a referral centre underwent standardized transthoracic echocardiographic examination including provocative manoeuvers. Under resting conditions, the length of mitral leaflets and distances between mitral valve coordinates and ventricular walls were blindly measured in parasternal long axis (PLAX) and apical three-chamber (3ch) views, both at early and late systole. Among 142 patients (mean age 59 ± 13 years, 42% women), 68 (42%) had resting or provocable LVOTO with maximal LVOT gradients ≥30 mmHg. Late-systolic distance between mitral leaflet tip and ventricular septum (TIS) was measurable in 137 participants (96%) in 3ch view and independently associated with LVOTO in multivariable logistic regression analysis. The area under the ROC curve of TIS for the identification of LVOTO was 0.91 [95% confidence interval (CI) 0.87-0.96]. TIS ≤ 14 mm yielded 97% sensitivity and 57% specificity regarding LVOTO. TIS >14 mm ruled out LVOTO with a negative predictive value of 95%. TIS ≤9 mm ruled in LVOTO with a positive predictive value of 92% (sensitivity 73%, specificity 95%). Among 43 patients with TIS between 10 and 14 mm, 35% had LVOTO. CONCLUSION: In our study, the novel echocardiographic parameter TIS showed high negative and positive predictive values for LVOTO in HCM. These exploratory results await confirmation in larger collectives and prospective investigations.

Outcomes of Patients With Hypertrophic Obstructive Cardiomyopathy and Pacemaker Implanted After Alcohol Septal Ablation.

BACKGROUND: Atrioventricular block is a frequent major complication after alcohol septal ablation (ASA). OBJECTIVES: The aim of this study was to evaluate the outcomes of patients with implanted permanent pacemaker (PPM) related to a high-grade atrioventricular block after ASA for hypertrophic obstructive cardiomyopathy. METHODS: We used a multinational registry (the Euro-ASA registry) to evaluate the outcome of patients with PPM after ASA. RESULTS: A total of 1,814 patients were enrolled and followed up for 5.0 ± 4.3 years (median = 4.0 years). A total of 170 (9.4%) patients underwent PPM implantation during the first 30 days after ASA. Using propensity score matching, 139 pairs (n = 278) constituted the matched PPM and non-PPM groups. Between the matched groups, there were no long-term differences in New York Heart Association functional class (1.5 ± 0.7 vs 1.5 ± 0.9, P = 0.99) and survival (log-rank P = 0.47). Patients in the matched PPM group had lower long-term left ventricular (LV) outflow gradient (12 ± 12 mm Hg vs 17 ± 19 mm Hg, P < 0.01), more pronounced LV outflow gradient decrease (81% ± 17% vs 72% ± 35%, P < 0.01), and lower LV ejection fraction (64% ± 8% vs 66% ± 8%, P = 0.02) and were less likely to undergo reintervention (re-ASA or myectomy) (log-rank P = 0.02). CONCLUSIONS: Patients with hypertrophic obstructive cardiomyopathy treated with ASA have a 9% probability of PPM implantation within 30 days after ASA. In long-term follow-up, patients with PPM had similar long-term survival and New York Heart Association functional class but lower LV outflow gradient, a more pronounced LV outflow gradient decrease, a lower LV ejection fraction, and a lower likelihood of reintervention compared with patients without PPM.

Prediction of Sudden Cardiac Arrest After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: ASA-SCARRE Risk Score.

This study aimed to derive a new score, the Alcohol Septal Ablation-Sudden Cardiac ARREst (ASA-SCARRE) risk score, that can be easily used to evaluate the risk of sudden cardiac arrest events (sudden cardiac death, resuscitation, or appropriate implantable cardioverter-defibrillator discharge) after alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy. We analyzed 1,834 patients from the Euro-ASA registry (49% men, mean age 57 ± 14 years) who were followed up for 5.0 ± 4.3 years (9,202 patient-years) after ASA. A total of 65 patients (3.5%) experienced sudden cardiac arrest events, translating to 0.72 events per 100 patient-years. The independent predictors of sudden cardiac arrest events were septum thickness before ASA (hazard ratio 1.09 per 1 mm, 95% confidence interval 1.04 to 1.14, p <0.001) and left ventricular outflow tract (LVOT) gradient at the last clinical checkup (hazard ratio 1.01 per 1 mm Hg, 95% confidence interval 1.01 to 1.02, p = 0.002). The following ASA-SCARRE risk scores were derived and independently predicted long-term risk of sudden cardiac arrest events: "0" for both LVOT gradient <30 mmHg and baseline septum thickness <20 mm; "1" for LVOT gradient ≥30 mm Hg or baseline septum thickness ≥20 mm; and "2" for both LVOT gradient ≥30 mm Hg and baseline septum thickness ≥20 mm. The C statistic of the ASA-SCARRE risk score was 0.684 (SE 0.030). In conclusion, the ASA-SCARRE risk score may be a useful and easily available clinical tool to predict risk of sudden cardiac arrest events after ASA in patients with hypertrophic obstructive cardiomyopathy.

Association between common cardiovascular risk factors and clinical phenotype in patients with hypertrophic cardiomyopathy from the European Society of Cardiology (ESC) EurObservational Research Programme (EORP) Cardiomyopathy/Myocarditis registry.

AIMS: The interaction between common cardiovascular risk factors (CVRF) and hypertrophic cardiomyopathy (HCM) is poorly studied. We sought to explore the relation between CVRF and the clinical characteristics of patients with HCM enrolled in the EURObservational Research Programme (EORP) Cardiomyopathy registry. METHODS AND RESULTS: 1739 patients with HCM were studied. The relation between hypertension (HT), diabetes (DM), body mass index (BMI), and clinical traits was analysed. Analyses were stratified according to the presence or absence of a pathogenic variant in a sarcomere gene. The prevalence of HT, DM, and obesity (Ob) was 37, 10, and 21%, respectively. HT, DM, and Ob were associated with older age (P<0.001), less family history of HCM (HT and DM P<0.001), higher New York Heart Association (NYHA) class (P<0.001), atrial fibrillation (HT and DM P<0.001; Ob p = 0.03) and LV (left ventricular) diastolic dysfunction (HT and Ob P<0.001; DM P = 0.003). Stroke was more frequent in HT (P<0.001) and mutation-positive patients with DM (P = 0.02). HT and Ob were associated with higher provocable LV outflow tract gradients (HT P<0.001, Ob P = 0.036). LV hypertrophy was more severe in Ob (P = 0.018). HT and Ob were independently associated with NYHA class (OR 1.419, P = 0.017 and OR 1.584, P = 0.004, respectively). Other associations, including a higher proportion of females in HT and of systolic dysfunction in HT and Ob, were observed only in mutation-positive patients. CONCLUSION: Common CVRF are associated with a more severe HCM phenotype, suggesting a proactive management of CVRF should be promoted. An interaction between genotype and CVRF was observed for some traits.

Age-related survival after alcohol septal ablation in hypertrophic obstructive cardiomyopathy.

AIMS: Since its introduction, alcohol septal ablation (PTSMA) was discussed as treatment option only in elderly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). We report on long-term follow-up after PTSMA with respect to patient's age. METHODS AND RESULTS: Between May 2000 and June 2017, we treated 952 consecutive HOCM patients with PTSMA; 133 (14.0%) patients were <40 years of age (Group A; mean age 30.3 ± 7.6; 26.3% female), 422 (44.3%) patients were between ≥40 and <60 years of age (Group B; mean age 50.6 ± 5.8; 27.0% female), and 397 (41.7%) patients were ≥60 years of age (Group C; 69.7 ± 6.1; 60.2% female). After PTSMA, need of pacemaker implantation was lowest in Group A (3.8%, P < 0.01 each) compared with Group B (9.2%) and Group C (14.1%) during hospital stay. One patient in Groups A and C died during hospital stay, each. Follow-up was longer in Group A (7.4 ± 5.5 years) compared with Group C (5.6 ± 4.8 years; P < 0.001) and comparable with Group B (6.5 ± 5.1 years). Mortality was highest in Group C (13.1%; P < 0.0001 each) compared with Group A (1.5%) and Group B (4.3%). In Group A, no patient died from cardiac reason, whereas five patients died from cardiac reasons in Group B and seven patients in Group C. Sudden cardiac death was not observed in Group A, whereas three patients in Group B and one patient in Group C suffered sudden cardiac death. CONCLUSIONS: Mortality after PTSMA is predominantly due to non-cardiac reasons and mainly observed in elderly patients. Survival in young patients is not affected by cardiac mortality. In experienced centres with careful patient selection, PTSMA is safe in young patients.

Alcohol dose in septal ablation for hypertrophic obstructive cardiomyopathy.

BACKGROUND: The aim of this study was to evaluate short- and long-term outcomes related to dose of alcohol administered during alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). Current guidelines recommend using 1-3 mL of alcohol administered in the target septal perforator artery, but this recommendation is based more on practical experience of interventionalists rather than on systematic evidence. METHODS: We included 1448 patients and used propensity score to match patients who received a low-dose (1.0-1.9 mL) versus a high-dose (2.0-3.8 mL) of alcohol during ASA. RESULTS: The matched cohort analysis comprised 770 patients (n = 385 in both groups). There was a similar occurrence of 30-day post-procedural adverse events (13% vs. 12%; p = 0.59), and similar all-cause mortality rates (0.8% vs. 0.5%; p = 1) in the low-dose group and the high-dose group, respectively. In the long-term follow-up (5.4 ± 4.5 years), a total of 110 (14%) patients died representing 2.58 deaths and 2.64 deaths per 100 patient-years in the low dose and the high dose group (logrank, p = 0.92), respectively. There were no significant differences in the long-term dyspnea and left ventricular outflow gradient between the two groups. Patients treated with a low-dose of alcohol underwent more subsequent septal reduction procedures (logrank, p = 0.04). CONCLUSIONS: Matched HOCM patients undergoing ASA with a low-dose (1.0-1.9 mL) or a high-dose (2.0-3.8 mL) of alcohol had similar short- and long-term outcomes. A higher rate of repeated septal reduction procedures was observed in the group treated with a low-dose of alcohol.

Sex-related differences in symptomatic patients with hypertrophic obstructive cardiomyopathy - Time for a new definition?

INTRODUCTION: Sex-related differences in diagnosis and treatment of hypertrophic obstructive cardiomyopathy (HOCM) are still unclear. Therefore, we analyzed baseline characteristics of symptomatic patients with indication for alcohol septal ablation (PTSMA) with respect to gender. METHODS AND RESULTS: Between 05/2000 and 06/2017 indication for PTSMA was seen in 1014 patients (420 (41.4%) women and 594 (58.6%) men). Women were older (61.4 ± 15.0 vs. 51.8 ± 13.6 years; p < 0.00001) and suffered more often from dyspnea NYHA III/IV (81.4% vs. 67.7%; p < 0.001), whereas angina pectoris and syncopes were comparable. Echocardiographic gradients were comparable in women (66.4 ± 39.1 mmHg at rest and 106.5 ± 46.6 mmHg at Valsalva) and men (62.7 ± 38.8 mmHg at rest and 103.7 ± 42.7 mmHg at Valsalva). Women had smaller absolute diameter of the left atrium (LA) (44.4 ± 6.9 vs. 47.2 ± 6.5 mm; p < 0.0001), septal thickness (IVS) (20.5 ± 4.1 vs. 21.4 ± 4.5 mm; p < 0.01), and left ventricular posterior wall thickness (LVPW) (12.7 ± 2.8 vs. 13.6 ± 2.9 mm; p < 0.0001). But, indexed for BSA the relationship reversed in LA (25.2 ± 4.3 mm/m2 in women vs. 23.1 ± 3.4 mm/m2), IVS (11.7 ± 2.7 mm/m2 in women vs. 10.6 ± 2.5 mm/m2) and LVPW (7.3 ± 1.7 mm/m2 in women vs. 6.7 ± 1.6 mm/m2), p < 0.00001 each. CONCLUSION: Women with HOCM and indication for PTSMA are older and more symptomatic with advanced disease progression. Reconsideration of disease definition and awareness maybe necessary in order to avoid delayed diagnosis and treatment of HOCM in women.

[Hypertrophic cardiomyopathy]. / Hypertrophe Kardiomyopathie.

Hypertrophic cardiomyopathy is the most common genetically determined cardiac disease with a prevalence of 0.2-0.6%. The most important pathophysiological phenomenon is dynamic obstruction predominantly of the left ventricular outflow tract in 70% of the patients. Clinical symptoms (e.g. dyspnea, angina pectoris and syncope) are extremely variable depending on changes in preload and afterload and an increased risk of sudden cardiac death particularly in younger patients. The diagnostic measures should be carried out with respect to a prognostic and symptomatic treatment with implantation of an implantable cardioverter defibrillator (ICD) in cases of increased risk of sudden cardiac death. When medication treatment fails, first-line treatment consists of septal ablation and surgical myectomy as a supplementary measure, depending on the underlying morphology and experience of the surgeon.

Multidisciplinary evaluation and management of obstructive hypertrophic cardiomyopathy in 2020: Towards the HCM Heart Team.

Patients with hypertrophic cardiomyopathy (HCM) exhibit a variable phenotype with ventricular hypertrophy as the cardinal manifestation and left ventricular (LV) outflow tract obstruction (LVOTO) as a key pathophysiologic determinant. Patients with severe LVOTO usually present with exertional dyspnea, exertional syncope, and heart failure symptoms, while successful relief of LVOTO by pharmacological or invasive interventions leads to a dramatic improvement in clinical status. Proper management of obstructive HCM remains challenging and poses numerous clinical dilemmas. Since the development of surgical myectomy over half a century ago, progress in the management of LVOTO in HCM has paralleled technological advances in genetic testing, cardiac imaging, arrhythmic prophylaxis, cardiac surgery and interventional cardiology. These changes have been incorporated in dedicated scientific guidelines on both sides of the Atlantic. However, either the 2011 American guidelines or the 2014 European guidelines remain largely based on expert consensus for lack of recommendations with level of evidence A regarding any of the treatment options commonly employed in HCM. Consequently, management of obstructive HCM patients remains largely subjective and dependent on clinical judgment, local expertise, and patient preference. Following the trend that has emerged for other cardiac diseases amenable to invasive interventions, adequate evaluation and management of obstruction in HCM today requires a multidisciplinary team capable of optimizing referral, choosing the best available options, minimizing complications and ensuring state-of-the-art results. The concept of an HCM Heart Team is coming of age. This review aims to provide an update of available pharmacologic and invasive options for the management of LVOTO in HCM, either in adulthood or in childhood, highlighting areas for multidisciplinary integration and future development.

Alcohol septal ablation in patients with severe septal hypertrophy.

OBJECTIVE: The current guidelines suggest alcohol septal ablation (ASA) is less effective in hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular hypertrophy, despite acknowledging that systematic data are lacking. Therefore, we analysed patients in the Euro-ASA registry to test this statement. METHODS: We compared the short-term and long-term outcomes of patients with basal interventricular septum (IVS) thickness <30 mm Hg to those with ≥30 mm Hg treated using ASA in nine European centres. RESULTS: A total of 1519 patients (57±14 years, 49% women) with symptomatic HOCM were treated, including 67 (4.4%) patients with IVS thickness ≥30 mm. The occurrence of short-term major adverse events were similar in both groups. The mean follow-up was 5.4±4.3 years and 5.1±4.1 years, and the all-cause mortality rate was 2.57 and 2.94 deaths per 100 person-years of follow-up in the IVS <30 mm group and the IVS ≥30 mm group (p=0.047), respectively. There were no differences in dyspnoea (New York Heart Association class III/IV 12% vs 16%), residual left ventricular outflow tract gradient (16±20 vs 16±16 mm Hg) and repeated septal reduction procedures (12% vs 18%) in the IVS <30 mm group and IVS ≥30 mm group, respectively (p=NS for all). CONCLUSIONS: The short-term results and the long-term relief of dyspnoea, residual left ventricular outflow obstruction and occurrence of repeated septal reduction procedures in patients with basal IVS ≥30 mm is similar to those with IVS <30mm. However, long-term all-cause and cardiac mortality rates are worse in the ≥30 mm group.

Short- and long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy in patients with mild left ventricular hypertrophy: a propensity score matching analysis.

AIMS: Based on European guidelines, alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) is indicated only in patients with interventricular septum (IVS) thickness >16 mm. The aim of this study was to evaluate the short- and long-term outcomes in ASA patients with mild hypertrophy (IVS ≤ 16 mm). METHODS AND RESULTS: We retrospectively evaluated 1505 consecutive ASA patients and used propensity score to match 172 pairs (344 patients) in groups IVS ≤ 16 mm or IVS > 16 mm. There was no occurrence of post-ASA ventriculoseptal defect in the whole cohort (n = 1505). Matched patients had 30-day mortality rate 0% in IVS ≤ 16 mm group and 0.6% in IVS > 16 mm group (P = 1). Patients in IVS ≤ 16 mm group had more ASA-attributable early complications (16% vs. 9%; P = 0.049), which was driven by higher need for pacemaker implantation (13% vs. 8%; P = 0.22). The mean follow-up was 5.4 ± 4.3 years and the annual all-cause mortality rate was 1.8 and 3.2 deaths per 100-patient-years in IVS ≤ 16 group and IVS > 16 group, respectively (log-rank test P = 0.04). There were no differences in symptom relief and left ventricular (LV) gradient reduction. Patients with IVS ≤ 16 mm had less repeated septal reduction procedures (log-rank test P = 0.03). CONCLUSION: Selected patients with HOCM and mild hypertrophy (IVS ≤ 16 mm) had more early post-ASA complications driven by need for pacemaker implantation, but their long-term survival is better than in patients with IVS >16 mm. While relief of symptoms and LV obstruction reduction is similar in both groups, a need for repeat septal reduction is higher in patients with IVS > 16 mm.