Gender Disparities in Clinical Outcome After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy in the Chinese Han Population: A Cohort Study.

BACKGROUND: Sex differences in the long-term prognosis of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing alcohol septal ablation (ASA) remain unclear, especially in the Chinese Han population. METHOD: This cohort study included 320 HOCM Chinese Han patients who underwent ASA because of symptomatic left ventricular outflow tract (LVOT) obstruction. Patients were grouped according to sex: females (mean±standard deviation age [SD] 50.7±6.8 years) and males (mean±SD age 52.6±7.3 years). Individuals were followed over the long term. RESULTS: Pre-procedure, women had more symptoms (New York Heart Association [NYHA] class III-IV 67.3% vs 56.3%, p=0.03), more atrial fibrillation (23.5% vs 14.6%, p=0.047) than men. Transient complete atrioventricular block after ASA was more common in woman than in men (34.0 vs 23.4%; p=0.048). Residual LVOT gradient, post-procedural residual left ventricular wall thickness, NYHA functional class, and adverse arrhythmic events were comparable between the two groups. The 10-year survival rate (77% vs 89%, p=0.037) and the annual adverse arrhythmic event rate (1.3% vs 0.4%, p<0.01) following ASA were significantly worse in women compared with men. Kaplan-Meier analysis showed a significantly lower survival in women compared with men (p=0.023). In multivariable modelling, female sex remained independently associated with higher all-cause mortality (hazard ratio, 1.12; 95% confidence interval, 1.08-1.27; p=0.03) when adjusted for age, NYHA class III-IV symptoms, and other cardiovascular comorbidities. CONCLUSIONS: Female patients with HOCM undergoing ASA tended to have more severe symptoms and adverse arrhythmic events. The 10-year survival rate after ASA was significantly worse in women compared with men with HOCM. Sex may need to be considered as an important factor in the clinical management of patients with symptomatic HOCM.

Choice of Septal Reduction Therapies and Alcohol Septal Ablation.

In patients with resting or provoked gradients and symptoms refractory to optimal medical therapy, alcohol septal ablation or surgical septal myectomy may be considered. Given the overall comparable outcomes after ablation and myectomy, there is, for many patients, equipoise between the two procedures. Septal ablation is performed with standard angioplasty guiding catheters, guidewires, and balloon catheters. In the Euro-ASA registry, NYHA functional class fell from 2.9 ± 0.5 to 1.6 ± 0.7 and gradient from 67 ± 36 to 16 ± 21 mm Hg at mean 3.9-year follow-up after septal ablation.

Transcatheter septal ablation in hypertrophic obstructive cardiomyopathy: a technical guide and review of published results.

Transcatheter alcohol septal ablation (ASA) treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) is based on the existence and degree of intraventricular obstruction. Patients with significant gradient and symptoms who do not respond to optimal medical therapy are eligible to gradient reduction through a surgical (septal myectomy) or a transcatheter (alcohol septal ablation) septal reduction. The latter encompasses occlusion of a septal branch perfusing the hypertrophied septum, which is involved in the generation of obstruction, by injecting ethanol into the supplying septal branch(es). ASA has been established as a highly effective and safe method and has outnumbered the surgical gold standard. Although the technique is straightforward, patient selection and some technical details may influence the efficacy and safety of the procedure. The technique is based on echocardiographic contrast guidance, which allows accurate target septal branch selection and optimisation of the result. Published long-term results from high-volume centres have confirmed the effectiveness of ASA and have shown excellent survival, which is comparable to that in the general population. Choice and performance of the surgical or interventional treatment should be implemented in highly specialised centres in terms of a heart-team approach, taking notice of anatomic characteristics as well as comorbidities. Involvement of all cases in international registries may reveal the individual merits and indications for the surgical and interventional treatment in HOCM.

Cystamine slows but not inverses the progression of monocrotaline-induced pulmonary arterial hypertension in rats.

Tissue transglutaminase (TG2) plays an important role in pulmonary arterial hypertension (PAH). Previous research indicate that TG2 and protein serotonylation catalyzed by TG2 are upregulated in PAH. Serotonin transporter inhibitor fluoxetine ameliorates PAH via inhibition of protein serotonylation. It is still unknown whether PAH is inhibited through direct inhibition of TG2. Therefore, the present study aimed to investigate the effects of TG2 inhibitor cystamine on monocrotaline-induced PAH in rats. Rats were treated with monocrotaline (60 mg·kg-1, i.p.) in combination with or without cystamine (20, 40 mg·kg-1·day-1, p.o.). The results showed that compared with monocrotaline alone, combination of monocrotaline with cystamine (40 mg·kg-1·day-1, p.o.) relieved right ventricle hypertrophy, inhibited pulmonary arteriolar remodeling, and downregulated protein expression of TG2, phosphorylated protein kinase B (Akt), and extracellular regulated protein kinase (ERK) at day 21. However, except for TG2 expression, these changes were not significantly inhibited by cystamine at day 35. In addition, cystamine dose-dependently enhanced the survival rate of rats injected with monocrotaline at day 35. The findings suggest that cystamine slows but not reverses monocrotaline-induced PAH in rats, which was largely associated with the inhibition of TG2 protein expression and Akt and ERK activation.

Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: A 16-Year Australian Single Centre Experience.

BACKGROUND: Alcohol septal ablation (ASA), is a well-established treatment for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). We report the acute, short and long-term clinical and echocardiographic outcomes of our experience in a single Australian centre over 16 years. METHODS: We retrospectively analysed consecutive patients presenting to our centre for ASA between March 2000 and July 2016. Local databases were interrogated along with direct patient or physician contact occurred where required. RESULTS: Alcohol septal ablation was performed in 80 patients with symptomatic, medication refractory HOCM (mean age 61±15 years; range 22-84 years; 50% male). All patients had transthoracic echocardiography prior to the procedure, within 48hours of the procedure, 6 weeks, 6 months, 1 year and yearly thereafter to a median follow-up of 80±40months. At baseline, mean resting and provoked LVOT gradients were 80±49mmHg and 97±40mmHg respectively. Compared with baseline, ASA led to a reduction in resting LVOT gradients at all time points, particularly at 2 days-52±41mmHg, p<0.001; 12 months-29±34mmHg, p<0.001; and last follow-up 12±21mmHg, p<0.001. Provoked LVOT gradients were also reduced at 2 days-64±44mmHg and last follow-up of 19±29mmHg, p<0.001. Compared to baseline (19.8±4.2mm), ASA was associated with a reduction in interventricular septal (IVS) thickness at all time intervals with last echocardiographic follow-up at 80 months being 16.0±4.9mm, (

Procedural complication and long term outcomes after alcohol septal ablation in patients with obstructive hypertrophic cardiomyopathy: data from China.

Data on procedural complications and long term survival after alcohol septal ablation (ASA) in Chinese patients with obstructive hypertrophic cardiomyopathy (HOCM) are lacking. We aimed to investigate long-term survival of HOCM patients after ASA and compared to the non-obstructive hypertrophic cardiomyopathy(NOHCM). A total of 233 patients with HOCM and a peak pressure gradient of ≥50 mm Hg at rest or with provocation were consecutively enrolled from Fuwai Hospital in China between 2000 and 2012. Another 297 patients without left ventricular outflow tract obstruction were regarded as control group. Periprocedural mortality of ASA were low (0.89%). Periprocedural lethal ventricular arrhythmia occurred in 9 patients (4.0%). Alcohol volume (RR 1.44, 95% CI: 1.03-2.03, P = 0.034) and age ≤40 years old (RR 4.63, 95% CI: 1.07-20.0, P = 0.040) were independent predictors for periprocedural lethal ventricular arrhythmia. The 10- year overall survival was 94.6% in the ASA group, similar with 92.9% in the NOHCM group (P = 0.930). In conclusion, periprocedural mortality and complications were rare in ASA. Long term survival after ASA were satisfactory and comparable to NOHCM. Patients under 40 years old should be more cautious undergoing ASA, for these patients were more likely to endure lethal ventricular arrhythmia during periprocedural period of ASA.

Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy: A Word of Balance.

The management of drug-refractory symptoms of obstructive hypertrophic cardiomyopathy has long been debated and is primarily centered on the choice between surgical myectomy and alcohol septal ablation. Decision making in these patients requires consideration of procedural risk, expertise and efficacy, and the long-term impact on patients' survival. Although there have been numerous reports on these procedures that may help guide decision making, these data continue to be self-reported and voluntary. Greater insight into the real-world experience for these therapies and how they should be applied in practice would be gained from mandatory reporting, akin to other multidisciplinary, transcatheter-based therapies.

Alcohol Septal Ablation to Reduce Heart Failure.

Hypertrophic cardiomyopathy is a commonly encountered inheritable cardiac disorder with variable phenotypic expression. Although most patients will have no or mild symptoms, 10% will develop heart failure symptoms refractory to medical management. This article discusses the mechanisms through which hypertrophic cardiomyopathy induces heart failure and how alcohol septal ablation can reverse each of these mechanisms to lead to clinical improvement.

Usefulness of Non-Anteroseptal Region Left Ventricular Hypertrophy Using Cardiac Magnetic Resonance to Predict Repeat Alcohol Septal Ablation for Refractory Obstructive Hypertrophic Cardiomyopathy.

We evaluated a cohort of patients treated with alcohol septal ablation (ASA) to identify predictive factors for repeat ASA. We compared 15 patients who underwent repeat ASA procedures (group R) with 69 patients not requiring repeat procedures (group S) in terms of clinical parameters and morphologic cardiac magnetic resonance. Group R showed higher number of hypertrophic segments (thickness ≥15 mm) in the basal left ventricular level (2.8 ± 1.7 vs 1.7 ± 0.8, p = 0.009) than group S. In the multivariate analysis, diuretics use (adjusted odds ratio 5.8, 95% confidential interval [CI] 1.04 to 32.2, p = 0.045) and the number of non-anteroseptal extended hypertrophy segments at the basal level were independent predictors of a repeat ASA procedure (adjusted odds ratio 3.64/segment, 95% CI 1.40 to 9.4, p = 0.008). One repeat ASA among 21 patients without non-anteroseptal hypertrophy and 1 repeat ASA among 29 patients without posteroseptal hypertrophy were observed; however, 7 of the 14 patients with ≥2 segments of non-anteroseptal hypertrophy received repeat ASA. In conclusion, cardiac magnetic resonance-based cross-sectional investigation elucidated non-anteroseptal hypertrophy (≥2 segments) to be a crucial predictor of repeat ASA. ASA is useful for patients with regional hypertrophy in the basal anteroseptal, but not posteroseptal region, and without heart failure requiring diuretics.

Alcohol septal ablation in hypertrophic cardiomyopathy utilizing a longitudinal 17-year study (mean 10.8). Observation follow-ups taken at a single medical centre.

BACKGROUND: Alcohol septal ablation (ASA) is a method of treatment in obstructive hypertrophic car-diomyopathy (HOCM), but there is little data on the long-term results of ASA and the natural course after treatment. The aim of the study was to evaluate the results of ASA in HOCM in multiannual observation, and its impact on patient survival, exercise capacity, electrical complications, and changes in the anatomy and function of the heart. METHODS: The study evaluated 47 patients with HOCM with a high left ventricular outflow tract (LVOT gradient) treated between 1997 and 2014 with ASA. Annual examinations evaluated the clinical condi-tion, at rest and with exercise electrocardiogram, Holter monitoring, echocardiography, the evolution of HOCM towards the dilated form, and the frequency of pacemaker implantation. RESULTS: The analysis included data from 34 patients under observation for 3 to 17 (mean 10.8) years. Their age at procedure was 21-65, a mean of 47 years. All patients had permanently reduced LVOT gradient with a mean of 77.36 ± 35.46 to 11.40 ± 10.85 and showed improvement in the performance I to II New York Heart Association. Two out of five deaths had possible cardiac etiology. Fifteen patients received a pacemaker or cardioverter implants. In 4 subjects the long-term observation revealed new wall contractility abnormalities, interpreted as a shift of HOCM to the dilated form. CONCLUSIONS: Alcohol septal ablation permanently eliminated the gradient in LVOT and improved the performance of patients, however it did not prevent a shift of HOCM to the dilated form. Pacemaker implantations are relatively frequent. (Cardiol J 2017; 24, 2: 125-130).

Conservative versus invasive treatment in hypertrophic obstructive cardiomyopathy: an echocardiography study.

AIM AND METHODS: The aim of our study was to compare the development of echocardiographic parameters and functional status of patients with hypertrophic obstructive cardiomyopathy (HOCM) treated conservatively (n = 41) or by alcohol septal ablation (ASA; n = 39). RESULTS: Left ventricular outflow tract gradient (LVOTG) decreased in the first year by 53.7±36.4 mmHg in ASA group versus 5.5±47.1 mmHg in conservatively treated group (p<0.001), in the third year by 53.1±41.4 mmHg versus 23.9±42.7 mmHg (p = NS) and in the fifth year, the reduction of LVOTG was 52.1±44.5 mmHg in ASA group and 3.0±63.2 mmHg in conservatively treated group (p<0.05).Change in NYHA class in the first year was -1.1±0.4 versus 0.1±0.5, in the third year -1.0±0.6 versus 0.1±0.4 and in the fifth year -0.8±0.5 versus 0.1±0.4 (all p<0.001). CONCLUSION: Our results showed for the first time that decline of LVOTG after ASA creates a favorable left ventricle remodeling and leads to significant improvement of functional status of HOCM patients in comparison with conservative treatment (Tab. 3, Fig. 2, Ref. 42).

Role of endocardial septal ablation in the treatment of hypertrophic obstructive cardiomyopathy.

Septal reduction therapy is accepted as a first therapeutic option for symptomatic drug-resistant hypertrophic obstructive cardiomyopathy (HOCM). Although, surgical septal myectomy is the gold standard method, alcohol septal ablation is a well-studied alternative approach in the patients with suitable anatomy. Endocardial septal ablation (ESA) therapy was relatively new defined modality and outcomes of the procedure were not clearly elucidated yet. We aimed to review the clinical aspects of ESA procedure and provide some historical background.

Prevalence of Non-Left Anterior Descending Septal Perforator Culprit in Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation.

Identifying the coronary branch that supplies the basal septum is the cornerstone for successful alcohol septal ablation (ASA). The basal septum is often supplied by septal perforator artery/arteries (SPA/SPAs) not originating from the left anterior descending (LAD) coronary artery. We aim to investigate the prevalence and significance of non-LAD septal "culprit" in patients undergoing ASA. A retrospective review of patients who underwent ASA from 2006 to 2014 was conducted. Procedural and midterm outcomes of patients who had ASA of LAD and non-LAD culprit SPA were reported. A total 89 patients were included in the analysis; 13 patients (15%) had ASA of non-LAD SPA. These patients were more likely to have a history of failed ASA, more than one SPA treated, more ethanol dose injected, longer procedures, and higher contrast use compared with those who had ASA of LAD-SPA. In-hospital outcomes, residual gradient, symptom improvement, and midterm mortality were similar in the 2 groups. In conclusion, in a cohort of patients undergoing ASA, 15% had ablation of SPA culprit that did not originate from the LAD. Half of these patients had previous unsuccessful ASA. Systematic screening for the ideal culprit SPA with nonselective coronary injection of echo contrast should be used to avoid incomplete or failed ASA.

Subclinical Myocardial Impairment Occurred in Septal and Anterior LV Wall Segments After Anthracycline-Embedded Chemotherapy and did not Worsen During Adjuvant Trastuzumab Treatment in Breast Cancer Patients.

In a previous study of breast cancer patients, we found changes in cardiac function and size during the early stages of adjuvant trastuzumab (Herceptin(®)) therapy. Here we present a subgroup analysis of this patient cohort. This subgroup received a anthracycline-embedded chemotherapy followed by at least 3 months up to 6 months of adjuvant Herceptin(®) therapy. Twenty-seven female breast cancer patients with Her-2/-neu overexpression were studied using conventional echocardiography and 2D speckle tracking. These methods were done before anthracycline-embedded chemotherapy, before adjuvant trastuzumab therapy, and both 3 and 6 months after the start of the therapy (T3, T6). The LV-EF (Simpson biplane) decreased significantly from before the chemotherapy to after the chemotherapy and further decreased after 3 months of trastuzumab therapy (66.2 ± 1.5 vs. 58.7 ± 1.2 vs. 55.6 ± 1.3 vs. 55.9 ± 1.5 %; p < 0.05). The stroke volume index remained constant after chemotherapy (22.0 ± 0.8 vs. 22.6 ± 1.3 ml/m(2); p = 0.9), but increased significantly during trastuzumab therapy (26.7 ± 1.1 and 27.3 ± 1.0 ml/m(2); p < 0.01). Global longitudinal strain exclusively decreased during chemotherapy (-21.0 ± 0.5 vs. -18.9 ± 0.5 %, p < 0.001). Regional longitudinal strain decreased significantly after chemotherapy in septal, anteroseptal, anterolateral, and apex segments. Mitral valve regurgitation increased during the whole treatment, but especially during trastuzumab. Right ventricular function decreased exclusively during chemotherapy. Anthracycline-embedded chemotherapy in patients with breast cancer led to a decrease in LV function, especially of the septal and anterior segments, and did not worsen during adjuvant trastuzumab treatment.

Crystal Structure of G Protein-coupled Receptor Kinase 5 in Complex with a Rationally Designed Inhibitor.

G protein-coupled receptor kinases (GRKs) regulate cell signaling by initiating the desensitization of active G protein-coupled receptors. The two most widely expressed GRKs (GRK2 and GRK5) play a role in cardiovascular disease and thus represent important targets for the development of novel therapeutic drugs. In the course of a GRK2 structure-based drug design campaign, one inhibitor (CCG215022) exhibited nanomolar IC50 values against both GRK2 and GRK5 and good selectivity against other closely related kinases such as GRK1 and PKA. Treatment of murine cardiomyocytes with CCG215022 resulted in significantly increased contractility at 20-fold lower concentrations than paroxetine, an inhibitor with more modest selectivity for GRK2. A 2.4 Å crystal structure of the GRK5·CCG215022 complex was determined and revealed that the inhibitor binds in the active site similarly to its parent compound GSK180736A. As designed, its 2-pyridylmethyl amide side chain occupies the hydrophobic subsite of the active site where it forms three additional hydrogen bonds, including one with the catalytic lysine. The overall conformation of the GRK5 kinase domain is similar to that of a previously determined structure of GRK6 in what is proposed to be its active state, but the C-terminal region of the enzyme adopts a distinct conformation. The kinetic properties of site-directed mutants in this region are consistent with the hypothesis that this novel C-terminal structure is representative of the membrane-bound conformation of the enzyme.

Survival after alcohol septal ablation versus conservative therapy in obstructive hypertrophic cardiomyopathy.

BACKGROUND: The impact of alcohol septal ablation (ASA) on the survival of patients with drug-refractory obstructive hypertrophic cardiomyopathy (HCM) remains unresolved. The aim of this study was to compare survival after ASA vs. conservative therapy. METHODS: We studied a consecutive cohort of 274 patients with severe drug-refractory obstructive HCM, 229 in ASA group and 45 in conservative group. The primary endpoint was a composite of all-cause mortality and aborted cardiac arrest. RESULTS: With a median follow-up of 4.3 years, primary endpoint occurred in 13 (5.7%) patients in the ASA group, and 8 (17.8%) patients in the conservative group. The 5- and 10-year survival free from primary endpoint of the ASA group (94.5% and 93.0%, respectively) was significantly better than that of the conservative group (78.3% and 72.2%, respectively, log-rank p = 0.009). Independent determinants of primary endpoint were ASA therapy (hazard ratio [HR] 0.22; 95% confidence interval [CI] 0.08-0.60; p = 0.003) and maximal septal thickness (HR 1.14; 95% CI 1.03-1.27; p = 0.011). CONCLUSIONS: In patients with severe drug-refractory obstructive HCM, survival after ASA is favorable and better than that of conservative therapy. ASA seems to improve survival.

Biventricular reverse remodeling after successful alcohol septal ablation for obstructive hypertrophic cardiomyopathy.

The aim of the present study was to investigate the long-term effects of alcohol septal ablation (ASA) on left ventricular (LV) and right ventricular (RV) remodeling in patients with obstructive hypertrophic cardiomyopathy (HC) using cardiovascular magnetic resonance (CMR). CMR was performed at baseline and 16 months after ASA in 38 patients with obstructive HC (mean age 48 ± 9 years) despite optimal medical treatment. ASA resulted in significant reductions of LV outflow tract gradient (mean 89 ± 22 vs 24 ± 12 mm Hg, p <0.001) and improvements in New York Heart Association functional class (p <0.001) during the follow-up period. LV remote mass and septal mass decreased from 98.34 ± 37.02 to 84.23 ± 34.71 g and from 77.56 ± 16.40 to 68.43 ± 14.02 g, respectively (p <0.001 for both) at 16-month follow-up. There were significant reductions of RV mass (mean 53.69 ± 7.12 vs 47.49 ± 6.17 g, p <0.001) and improvements in RV end-diastolic volume (mean 110.58 ± 22.47 vs 124.22 ± 24.17 ml, p <0.001) and the RV ejection fraction (p <0.001) during 16-month follow-up. Linear regression analysis showed that LV outflow tract gradient reduction was correlated significantly with LV remote mass reduction (r = 0.475, p = 0.003) and RV mass reduction (r = 0.535, p = 0.001) at 16-month follow-up. In conclusion, successful ASA can lead to positive biventricular reverse remodeling, showing significant reductions of RV and LV mass as well as increased RV and LV end-diastolic volumes during follow-up.

Unjailing of the septal perforator using a rotational atherectomy device prior to alcohol septal ablation in a patient with symptomatic hypertrophic obstructive cardiomyopathy.

We report a novel approach in which successful unjailing of the septal perforator was performed through the side branch of a coronary stent using a rotational atherectomy device for the purpose of alcohol septal ablation in a patient with symptomatic hypertrophic obstructive cardiomyopathy.

Inaccuracy of transthoracic echocardiography for the identification of right-sided vegetation in patients with no history of intravenous drug abuse or cardiac device insertion.

OBJECTIVE: The use of transthoracic echocardiography (TTE) to identify right-sided infective endocarditis (RSIE) vegetation is controversial. Data are scarce for patients with no history of intravenous drug abuse (IVDA) or cardiac device insertion. This study analysed the consistency of presurgical echocardiographic results with surgical findings for vegetation identification, and the factors that influence accuracy of echocardiography. METHODS: This retrospective trial divided infective endocarditis (IE) patients into three subgroups according to the results of their presurgical TTE: left-sided native IE (LSNIE), left-sided prosthetic valve IE (LSPIE) and RSIE. The accuracy of TTE was tested by comparing vegetation (number and location), detected presurgery by TTE, with actual findings during surgery. RESULTS: In total, 416 patients were analysed, 322 with LSNIE, 31 with LSPIE and 63 with RSIE. Consistency between TTE findings and surgical results was lower in the RSIE group compared with the LSPIE and LSNIE groups. Consistency was lowered by the presence of vegetation in multiple locations and atypical distribution--both of which were increased in the RSIE group. The chance of vegetation in both sides of the heart rose with increased numbers of vegetation locations in RSIE patients. A high proportion of RSIE patients had congenital heart defects, mostly ventricular septal defects. CONCLUSIONS: TTE may be unsuitable for RSIE patients with no history of IVDA or cardiac device insertion, because multifocal and atypically distributed vegetation may influence detection accuracy.