Higher Left Ventricular Outflow Tract Research Articles

Natural history and outcomes in paediatric RASopathy-associated hypertrophic cardiomyopathy.

This study aimed to describe the natural history and predictors of all-cause mortality and sudden cardiac death (SCD)/equivalent events in children with a RASopathy syndrome and hypertrophic cardiomyopathy (HCM). This is a retrospective cohort study from 14 paediatric cardiology centres in the United Kingdom and Ireland. We included children <18years with HCM and a clinical and/or genetic diagnosis of a RASopathy syndrome [Noonan syndrome (NS), NS with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and NS with loose anagen hair (NS-LAH)]. One hundred forty-nine patients were recruited [111 (74.5%) NS, 12 (8.05%) NSML, 6 (4.03%) CS, 6 (4.03%) CFCS, 11 (7.4%) Noonan-like syndrome, and 3 (2%) NS-LAH]. NSML patients had higher left ventricular outflow tract (LVOT) gradient values [60 (36-80) mmHg, P=0.004]. Over a median follow-up of 197.5 [inter-quartile range (IQR) 93.58-370] months, 23 patients (15.43%) died at a median age of 24.1 (IQR 5.6-175.9) months. Survival was 96.45% [95% confidence interval (CI) 91.69-98.51], 90.42% (95% CI 84.04-94.33), and 84.12% (95% CI 75.42-89.94) at 1, 5, and 10years, respectively, but this varied by RASopathy syndrome. RASopathy syndrome, symptoms at baseline, congestive cardiac failure (CCF), non-sustained ventricular tachycardia (NSVT), and maximal left ventricular wall thickness were identified as predictors of all-cause mortality on univariate analysis, and CCF, NSVT, and LVOT gradient were predictors for SCD or equivalent event. These findings highlight a distinct category of patients with Noonan-like syndrome with a milder HCM phenotype but significantly worse survival and identify potential predictors of adverse outcome in patients with RASopathy-related HCM.

Natural history and predictors of all-cause mortality and major arrhythmic cardiac events in pediatric RASopathy associated hypertrophic cardiomyopathy

Abstract The RASopathies are a group of developmental disorders caused by germline variants in components of the RAS-MAPK pathway, commonly associated with hypertrophic cardiomyopathy (HCM). The aim of this study was to describe the natural history and predictors of all-cause mortality and major arrhythmic cardiac events (MACE) in a large, multi-centre cohort of paediatric patients with a RASopathy syndrome and HCM. One-hundred-and-forty-nine patients were included (111 (74.5%) Noonan Syndrome (NS); 12 (8.05%) Noonan Syndrome with Multiple Lentigines (NSML); 6 (4.03%) Costello Syndrome (CS); 6 (4.03%) Cardiofaciocutaneous Syndrome (CFCS); and 14 (9.4%) with Noonan-like syndrome patients). NSML patients had higher maximal left ventricular wall thickness (MLVWT) (z score 17.02 (10.57-32.78), p=0.004] and higher left ventricular outflow tract (LVOT) gradient values (60mmHg, 36-80, p=0.019), with no other significant echocardiographic differences between RASopathy syndromes. Over a median follow up of 197.5 months (93.58-370), 23 patients (15.43%) died, at a median age of 48.94 months (3.29-175.84). Overall survival was 96.45% (91.69-98.51), 90.42% (84.04-94.33) and 84.12 (75.42-89.94) at 1, 5 and 10 years, respectively, but this was varied according to RASopathy syndrome. RASopathy syndrome, specifically Noonan-like syndrome (Hazard ratio 4.18, p=0.032) and congestive cardiac failure admission (Hazard ratio 7.35, p=0.037) were independent predictors of all-cause mortality and LVOT gradient was an independent predictor for MACE (Hazard ratio 1.02, p=0.025). These findings highlight a distinct category of patients with Noonan-like syndrome with a milder HCM phenotype but significantly worse survival and identify predictors of adverse outcome in patients with RASopathy-related HCM.

Abstract 12016: Rare Variants in APOE Gene Are Associated With Disease-Onset and Outcomes of Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease and may lead to tragic outcomes such as sudden cardiac death and heart failure. Previous studies have shown that HCM patients undergo significant lipid-related metabolic reprogramming. But whether lipid gene variants affect the diagnosis and prognosis of HCM patients remains unclear. Methods and Results: Whole-exome sequencing was performed in 985 patients with HCM and 759 non-HCM controls to search for lipid gene variants. The APOE rare variants were more prevalent in patients with HCM than controls (odds ratio, 4.91, P &lt; 0.001). Patients with APOE rare variants have higher left ventricular outflow tract gradient (LVOTG) (71.0 VS 38.0 mmHg, P = 0.035), higher triglycerides (1.59 VS 1.32 mmol/L, P = 0.051) and lower lipoprotein a (65.5 vs 113 mg/L, P = 0.076) in peripheral blood. APOE carriers also had elevated free fatty acids in 290 surgically resected myocardial tissue lipidomics data (P = 0.008). With a median follow-up time of 5.10 years, HCM patients with APOE rare variants were more likely to experience cardiovascular death (adjusted HR 4.8, P = 0.001) and all-cause death (adjusted HR 3.5, P = 0.008). Conclusion: Our cohort data indicated that rare variants of APOE are associated with altered lipid metabolism in peripheral blood as well as myocardial tissue, increased LVOTG, and greater risk of HCM disease-onset as well as poor prognosis. We proposed that APOE might be associated with HCM and that its contribution to myocardial hypertrophy through lipotoxicity may be an emerging mechanism for HCM pathogenesis and progression.

Is There a Sex Difference in the Prognosis of Hypertrophic Cardiomyopathy? A Systematic Review and Meta-Analysis.

Background It is still unclear whether there is a sex difference in the prognosis of patients with hypertrophic cardiomyopathy (HCM). Therefore, we performed a meta-analysis to elucidate the association between sex and adverse outcomes in patients with HCM. Methods and Results The PubMed, Cochrane Library, and Embase databases were used to search for studies on sex differences in prognosis in patients with HCM up to August 17, 2021. Summary effect sizes were calculated using a random effects model. The protocol was registered in PROSPERO (International prospective register of systematic reviews) (registration number- CRD42021262053). A total of 27 cohorts involving 42 365 patients with HCM were included. Compared with male subjects, female subjects had a higher age at onset (mean difference=5.61 [95% CI, 4.03-7.19]), a higher left ventricular ejection fraction (standard mean difference=0.09 [95% CI, 0.02-0.15]) and a higher left ventricular outflow tract gradient (standard mean difference=0.23 [95% CI, 0.18-0.29]). The results showed that compared with male subjects with HCM, female subjects had higher risks of HCM-related events (risk ratio [RR]=1.61 [95% CI, 1.33-1.94], I2=49%), major cardiovascular events (RR=3.59 [95% CI, 2.26-5.71], I2=0%), HCM-related death (RR=1.57 [95% CI, 1.34-1.82], I2=0%), cardiovascular death (RR=1.55 [95% CI, 1.05-2.28], I2=58%), noncardiovascular death (RR=1.77 [95% CI, 1.46-2.13], I2=0%) and all-cause mortality (RR=1.43 [95% CI, 1.09-1.87], I2=95%), but not atrial fibrillation (RR=1.13 [95% CI, 0.95-1.35], I2=5%), ventricular arrhythmia (RR=0.88 [95% CI, 0.71-1.10], I2=0%), sudden cardiac death (RR=1.04 [95% CI, 0.75-1.42], I2=38%) or composite end point (RR=1.24 [95% CI, 0.96-1.60], I2=85%). Conclusions Based on current evidence, our results show significant sex-specific differences in the prognosis of HCM. Future guidelines may emphasize the use of a sex-specific risk assessment for the diagnosis and management of HCM.

Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: A case Report

Alcohol septal ablation (ASA) has shown to be a safe and effective procedure for treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) for more than 20 years with results similar to those of surgical myectomy. The first septal branch of the left anterior descending artery (LAD) is located and 96% alcohol is instilled to induce an artificial myocardial infarction and necrosis at the base of the hypertrophied septum. Now we present our first experience of a patient with HOCM with a very high left ventricular outflow tract gradient who had successful alcohol septal ablation. Cardiovasc j 2022; 15(1): 95-99

A novel risk model to predict all-cause mortality in patients undergoing percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy

Background and purpose: Hypertrophic obstructive cardiomyopathy (HOCM) is a global genetic myocardial disease. In clinical practice, an indicator that could be used to identify suitable patients for percutaneous transluminal septal myocardial ablation (PTSMA) and assess their long-term prognosis is important for cardiologists. HOCM patients undergoing PTSMA, poor long-term prognosis has been associated with higher left ventricular outflow tract gradient (LVOTG) and interventricular septal thickness (IVST). In this retrospective, multicenter study, we aimed to investigate the association between TG (TG = IVS thickness × LVOT gradient) index and acute- or long-term outcomes of HOCM patients after PTSMA and further investigate the interaction effects of LVOTG and IVST. Methods: The study design is based on four tertiary centers from Mid-China, and a total of 284 HOCM patients (132 males, average age 54.80 ± 11.98 years) were treated with PTSMA. A new clinic index (TG = IVS thickness × LVOT gradient) was designed. Both 30-day major cardiovascular adverse events and all-cause mortality of the HOCM patients were analyzed. Cox proportional hazards regression model adjusting for potential risk factors was applied to explore the hazard ratio (HR) for all-cause mortality. Results: Total alcohol injection volume was 2.201 ± 1.025 mL. LVOTG and IVST were reduced to 40.11 ± 24.44 mmHg and 17.68 ± 4.07 mm at the last clinical check-up, respectively. Patients with low IVST (≤20 mm) or low TG index (≤1,683) had a higher rate of PTSMA-contributable complications and a higher need for a permanent pacemaker. Within the 903 patient-years follow-up, a total of 21 (9.8%) deaths occurred. The number of deaths per 100 patient-years was 0.65 and 4.06 in the high versus low TG index groups. The 8-year OS rate was 48.95% (95% CI = 39.07%–57.75%) versus 82.63% (95% CI = 74.99%–86.66%) in the high versus low TG groups, respectively (log-rank P &lt; 0.001). The patients with both high LVOTG (&gt;82 mmHg) and high IVST had the highest risk of all-cause mortality (HR: 18.63 vs low LVOTG, 95% CI = 1.09–319.15). Conclusions: The 8-year OS rate was markedly higher in patients with a low TG index (≤1,683) (48.95%) versus in patients with a high TG index (&gt;1,683 group) (82.63%). The TG index could be a useful tool in the evaluation of HOCM patients for suitability for PTSMA.

Cardiovascular evaluation of pregnant women with hypertrophic cardiomyopathy.

The effect of physiological circulatory changes during pregnancy on hypertrophic cardiomyopathy (HCM) has been reported with limited data. This study aimed to provide information regarding outcomes of pregnant women with HCM and to identify predictors of major adverse cardiac event (MACE). Atotal of 45pregnancies with HCM were retrospectively reviewed. The primary endpoint was aMACE that occurred within an 8‑week period after delivery, including maternal death, heart failure (HF), syncope, and malignant ventricular arrhythmias (VAs). Baseline and outcome data were analyzed for all patients. Patients with and without MACE were compared, and patients with obstructive HCM were compared with those who had non-obstructive HCM. The study population was divided into two subgroups of patients having or not having an implantable cardioverter defibrillator implantation (ICD). At least one MACE occurred in 11patients (24.4%); six patients developed HF (13.3%), six had aventricular tachyarrhythmia (13.3%), and two had syncope (4.4%). New York Heart Association functional class of ≥ II, presence of HF signs before pregnancy, increased left ventricular outflow tract (LVOT) gradient were significantly associated with MACE. Fatal VAs were seen during pregnancy inone of five HCM patients with ICD. In the ROC curve analysis, an LVOT gradient higher than 53.5 mm Hg predicted the presence of MACE with asensitivity of 90.9% and aspecificity of 73.5%. This study is the largest series in the literature representing pregnant women who had HCM and ICD. The current data suggest that HF and high LVOT gradients are important risk factors for the development of cardiac complications.

Application of the proximal isovelocity surface area method for estimation of the effective orifice area in aortic stenosis

Although the echocardiographic effective orifice area (EOA) calculated using the continuity equation is widely used for the assessment of severity in aortic stenosis (AS), the existence of high flow velocity at the left ventricular outflow tract (LVOT) potentially causes its overestimation. The proximal isovelocity surface area (PISA) method could be an alternative tool for the estimation of EOA that limits the influence of upstream flow velocity. EOA was calculated using the continuity equation (EOACont) and PISA method (EOAPISA), respectively, in 114 patients with at least moderate AS. The geometric orifice area (GOA) was also measured using the planimetry method in 51 patients who also underwent three-dimensional transesophageal echocardiography. Patients were divided into two groups according to the median LVOT flow velocity. EOAPISA could be obtained in 108 of the 114 patients (95%). Although there was a strong correlation between EOACont and EOAPISA (r = 0.78, P < 0.001), EOACont was statistically significantly larger than EOAPISA (0.86 ± 0.33 vs 0.75 ± 0.29 cm2, P < 0.001). Both EOACont and EOAPISA similarly correlated with GOA (r = 0.70, P < 0.001 and r = 0.77, P < 0.001, respectively). However, a fixed bias, which is hydrodynamically supposed to exist between EOA and GOA, was not observed between EOACont and GOA. In contrast, there was a negative fixed bias between EOAPISA and GOA with smaller EOAPISA than GOA. The difference between EOACont and GOA was significantly greater with a larger EOACont relative to GOA in patients with high LVOT flow velocity than in those without (0.16 ± 0.25 vs - 0.07 ± 0.10 cm2, P < 0.001). In contrast, the difference between EOAPISA and GOA was consistent regardless of the LVOT flow velocity (- 0.07 ± 0.12 vs - 0.07 ± 0.15 cm2, P = 0.936). The PISA method was applied to estimate EOA in patients with AS. EOAPISA could be an alternative parameter for AS severity grading in patients with high LVOT flow velocity in whom EOACont would potentially overestimate the orifice area.

Geometry and flow in ascending aortic aneurysms are influenced by left ventricular outflow tract orientation: Detecting increased wall shear stress on the outer curve of proximal aortic aneurysms

BackgroundThe geometrical characterization of ascending thoracic aortic aneurysms in clinical practice is limited to diameter measurements. Despite growing interest in hemodynamic assessment, its relationship with ascending thoracic aortic aneurysm pathogenesis is poorly understood. This study examines the relationship between geometry of the ventriculo-aortic junction and blood flow patterns in ascending thoracic aortic aneurysm disease. MethodsThirty-three patients with ascending thoracic aortic aneurysms (exclusions: bicuspid aortic valves, connective tissue disease) underwent 4-dimensional flow magnetic resonance imaging. After image segmentation, geometrical parameters were measured, including aortic curvature, tortuosity, length, and diameter. A unique angular measurement made by the trajectory of the left ventricular outflow tract axis and the proximal aorta was also conducted. Velocity profiles were quantitatively and qualitatively analyzed. In addition, 11 patients (33%) underwent wall shear stress mapping of the ascending thoracic aortic aneurysm region using computational fluid dynamics simulation. ResultsGreater left ventricular outflow tract aortic angles were associated with larger aortic diameters at the levels of the sinus (coefficient = 0.387, P = .014) and ascending aorta (coefficient = 0.284, P = .031). Patients with left ventricular outflow tract aortic angles greater than 60° had marked asymmetric flow acceleration on the outer curvature in the proximal aorta, ascertained from 4-dimensional flow analysis. For patients undergoing computational fluid dynamics assessment, regression analysis found that higher left ventricular outflow tract aortic angles were associated with significantly higher wall shear stress values in the outer curve of the aorta (coefficient 0.07, 95% confidence interval 0.04-0.11, P = .002): Angles greater than 50° yielded time-averaged wall shear stress values greater than 2.5 Pa, exhibiting a linear relationship. ConclusionsOur findings strengthen the hypothesis of flow-mediated ascending thoracic aortic aneurysm disease progression and that left ventricular outflow tract aortic angle may be a predictor of disease severity.

Is anterior mitral valve leaflet length important in outcome of septal myectomy for obstructive hypertrophic cardiomyopathy?

ObjectivesElongation of mitral valve leaflets is a phenotypic feature of hypertrophic cardiomyopathy, and some surgeons advocate plication of the anterior leaflet at the time of septal myectomy. The present study investigates mitral valve leaflet length and outcomes of patients undergoing septal myectomy for obstructive hypertrophic cardiomyopathy. MethodsWe reviewed the records and echocardiograms of 564 patients who underwent transaortic septal myectomy for obstructive hypertrophic cardiomyopathy between February 2015 and April 2018. Extended septal myectomy without plication of the anterior leaflet was the standard procedure. From intraoperative prebypass transesophageal echocardiograms, we measured anterior and posterior mitral valve leaflets and their coaptation length. For comparison, we performed these mitral valve leaflet measurements in 90 patients who underwent isolated coronary artery bypass grafting and 92 patients undergoing aortic valve replacement in the same period. Among patients with hypertrophic cardiomyopathy undergoing septal myectomy, we assessed left ventricular outflow tract gradient relief and 1-year survival in relation to leaflet length. ResultsMedian patient age (interquartile range) was 60.3 (50.2-67.7) years, and 54.1% were male. Concomitant mitral valve repair was performed in 36 patients (6.4%), and mitral valve replacement was performed in 8 patients (1.4%), primarily for intrinsic mitral valve disease. Patients in the hypertrophic cardiomyopathy cohort had significantly longer mitral valve leaflet measurements compared with patients undergoing coronary artery bypass grafting or aortic valve replacement (P < .001 for all 3 measurements). Preoperative resting left ventricular outflow tract gradients were not related to leaflet length (<30 mm, median 49 [21, 81.5] mm Hg vs ≥30 mm, 50.5 [21, 77] mm Hg; P = .76). Further, gradient reduction after myectomy was not related to leaflet length; patients with less than 30 mm anterior leaflet length had a median gradient reduction of 33 (69, 6) mm Hg compared with 36.5 (62, 6) mm Hg for patients with leaflet length 30 mm or more (P = .36). Anterior mitral valve leaflet length was not associated with increased 1-year mortality (P = .758). ConclusionsOur study confirms previous findings that patients with hypertrophic cardiomyopathy have slight (5 mm) elongation of mitral valve leaflets. In contrast to other reports, increased anterior mitral valve leaflet length was not associated with higher left ventricular outflow tract gradients. Importantly, we found no significant relationship between anterior mitral valve leaflet length and postoperative left ventricular outflow tract resting gradients or gradient relief. Thus, in the absence of intrinsic mitral valve disease, transaortic septal myectomy with focus on extending the excision beyond the point of septal contact is sufficient for almost all patients.

Abstract 13481: South Asian-specific MYBPC3 25bp Intronic Deletion Carriers Demonstrate Hypercontractility and Impaired Diastolic Function Under Exercise Stress

Introduction: A 25bp intronic deletion in MYBPC3 ( Δ25bp ), present in 6% of US South Asians, is a risk allele for late onset left ventricular (LV) dysfunction and hypertrophy. Hypothesis: Asymptomatic Δ25bp carriers have detectable subclinical pathology to development of LV hypercontractility and impaired relaxation. Methods: To evaluate Δ25bp carriers for changes in cardiac function with bicycle exercise stress echocardiography and continuous cardiac monitoring, 16 Δ25bp male carriers (51±2 years) and 10 age- and sex-matched non-carrier (NCs) controls (50±3 years) participated in this pilot study. Of 16 Δ25bp carriers, six carried an additional pathogenic variant D389V in MYBPC3 . Included subjects had no uncontrolled comorbidities. Regression analysis and two-way ANOVA were performed, and 95% confidence interval (CI) and p values were reported. Results: Baseline echocardiographic parameters as well as baseline and monitored exercise heart rate and blood pressure were similar in both groups. The estimated effect of exercise stress and genotype showed that Δ25bp carriers had significantly higher ejection fraction (%) (CI: 4.03±1.64; p&lt;0.0001) and higher LV outflow tract peak velocity (m/s) (CI: 0.15±0.06; p&lt;0.0001) in comparison to NCs. Additionally, stress-induced LV end diastolic diameter did not increase in Δ25bp carriers as compared to NCs with a significant difference between the groups (CI: 0.22±0.11; p=0.0002). E/A ratio, a marker of diastolic function, significantly decreased with exercise in Δ25bp carriers (slope: -0.002; p=0.005) but showed non-significant change in the NCs (slope: -0.0006; p=0.428). Right ventricular systolic excursion velocity s' (m/s) as a marker of right ventricle function increased similarly in both groups, although tricuspid annular plane systolic excursion (cm) increased more dramatically in carriers (slope: 0.004; p=0.0002). Sub-analysis of Δ25bp vs Δ25bp + D389V did not reveal any differences. Conclusions: LV hypercontractility under exercise stress conditions with evidence of diastolic impairment at high workloads is evident among asymptomatic carriers of MYBPC3 Δ25bp allele, suggesting MYBPC3 Δ25bp as a risk allele with sub-clinical pathology prior to late onset LV dysfunction in South Asians .

Influence of Gender on Clinical Characteristics and Outcomes in Chinese Patients With Hypertrophic Cardiomyopathy

Gender plays a crucial role in the prevalence, clinical presentation, management and outcomes of various cardiovascular diseases. The aim of this study was to evaluate the impact of gender on clinical manifestations and outcomes in the Chinese patients with hypertrophic cardiomyopathy (HCM). We evaluated 576 Chinese patients (316 males) who were diagnosed with HCM at West China Hospital from 2008 to 2016 and followed over 3.2 ± 2.3 years. Compared to male patients, female patients were older (57.2 ± 16.7 years vs. 53.0 ± 15.7 years, P=0.002) and more symptomatic [New York Heart Association class III-IV symptoms 46.9% vs. 30.7%, P < 0.001] at the time of diagnosis, and had higher left ventricular outflow tract gradient at rest [33 (12-58) mmHg vs. 24 (8-42) mmHg, P=0.007]. During the follow-up period, survival analysis showed no significant differences in the incidences of all-cause mortality (P=0.657) and cardiovascular mortality (P=0.214) but the rate of rehospitalization due to heart failure was higher in females than in males (P=0.015). Multivariable Cox analysis showed that left ventricular ejection fraction (hazard ratio [HR], 0.96 [95% confidence interval [CI], 0.94-0.99]; P=0.003) and New York Heart Association class III-IV (HR, 2.86 [95% CI, 1.38-5.94]; P=0.005) were independently associated with cardiovascular mortality. Compared to males, females were older and more symptomatic at presentation, and had higher risk of progression to heart failure in Chinese HCM patients but there were no differences in cardiovascular mortality.

Inconsistency in aortic stenosis severity between CT and echocardiography: prevalence and insights into mechanistic differences using computational fluid dynamics

ObjectivesThe aims of this study were to evaluate the inconsistency of aortic stenosis (AS) severity between CT aortic valve area (CT-AVA) and echocardiographic Doppler parameters, and to investigate potential underlying...

Alcohol septal ablation in hypertrophic obstructive cardiomyopathy: a case with a very high left ventricular outflow tract gradient

For more than years alcohol septal ablation ASA has shown to be a safe and effective procedure in the treatment of hypertrophic obstructive cardiomyopathy HOCM with results similar to those of surgical myectomy To our knowledge we present the first documented case of a HOCM with a very high left ventricular outflow tract LVOT gradient gt mm Hg managed with ASA with a decrease of gt of gradient after the procedure

Hypertrophic cardiomyopathy with dynamic obstruction and high left ventricular outflow gradients associated with paradoxical apical ballooning.

Acute left ventricular (LV) apical ballooning with normal coronary angiography occurs rarely in obstructive hypertrophic cardiomyopathy (OHCM); it may be associated with severe hemodynamic instability. We searched for acute LV ballooning with apical hypokinesia/akinesia in databases of two HCM treatment programs. Diagnosis of OHCM was made by conventional criteria of LV hypertrophy in the absence of a clinical cause for hypertrophy and mitral-septal contact. Among 1519 patients, we observed acute LV ballooning in 13 (0.9%), associated with dynamic left ventricular outflow tract (LVOT) obstruction and high gradients, 92±37mmHg, 10 female (77%), age 64±7years, LVEF 31.6±10%. Septal hypertrophy was mild compared to that of the rest of our HCM cohort, 15 vs 20mm (P<0.00001). An elongated anterior mitral leaflet or anteriorly displaced papillary muscles occurred in 77%. Course was complicated by cardiogenic shock and heart failure in 5, and refractory heart failure in 1. High-dose beta-blockade was the mainstay of therapy. Three patients required urgent surgical relief of LVOT obstruction, 2 for refractory cardiogenic shock, and one for refractory heart failure. In the three patients, surgery immediately normalized refractory severe LV dysfunction, and immediately reversed cardiogenic shock and heart failure. All have normal LV systolic function at 45-month follow-up, and all have survived. Acute LV apical ballooning, associated with high dynamic LVOT gradients, may punctuate the course of obstructive HCM. The syndrome is important to recognize on echocardiography because it may be associated with profound reversible LV decompensation.

Leukocyte telomere length correlates with hypertrophic cardiomyopathy severity

Telomere length is a marker of biological aging. Short leukocyte telomere length has been associated with various conditions including cardiovascular disorders. Here, we evaluated if patients with hypertrophic cardiomyopathy have altered leukocyte telomere length and whether this is associated with disease severity. A quantitative polymerase chain reaction-based method was used to measure peripheral blood leukocyte telomere length in 59 healthy control subjects and a well-characterized cohort of 88 patients diagnosed with hypertrophic cardiomyopathy: 32 patients with non-obstructive cardiomyopathy (HNCM) and 56 patients with obstructive cardiomyopathy (HOCM). We observed shorter leukocyte telomeres in both HNCM and HOCM patients compared to healthy controls. Furthermore, leukocyte telomere length was inversely associated with HCM even after adjusting for age and sex. Telomere length of HOCM patients was also inversely correlated with left ventricular outflow tract obstruction. Therefore, HOCM patients were categorized by tertiles of telomere length. Patients in the first tertile (shortest telomeres) had a significantly increased left ventricular posterior wall thickness at end-diastole and higher left ventricular outflow tract gradients, whereas the left ventricular end-diastolic diameter was lower compared with patients in the second and third tertile. In summary, telomere length is associated with the severity of the disease in the HOCM subtype.

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

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. 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. 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. 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).

Predictors of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement With the SAPIEN 3.

The aim of this study was to identify predictors of permanent pacemaker implantation (PPMI) following transcatheter aortic valve replacement (TAVR) with a balloon-expandable transcatheter valve (Edwards SAPIEN 3). New-onset conduction disturbances requiring PPMI remain a major concern following TAVR. Predictors are not yet well defined. The influence of angiographic implantation depth, device landing zone calcium volume, oversizing, pre- and post-dilation, and baseline conduction disturbances on PPMI rate was analyzed in 229 patients undergoing TAVR with the SAPIEN 3 device. PPMI was performed in 14.4% of patients. Patients requiring PPMI had higher left ventricular outflow tract (LVOT) calcium volume in the area below the left coronary cusp (LVOTLC) and the area below right coronary cusp (LVOTRC) (LVOTLC median calcium 23.7 mm3 vs. 3.0 mm3; p< 0.001; LVOTRC median calcium 6.6 mm3 vs. 0.3 mm3; p=0.014), a higher prevalence of pre-existing right bundle branch block (15% vs. 2%, p= 0.004), and lower implantation depth (ventricular portion of the stent frame 29 ± 12% vs. 21 ± 5%; p< 0.001). On multivariate regression analysis, LVOTLC calcium volume >13.7 mm3, LVOTRC calcium volume >4.8 mm3, pre-existing right bundle branch block, and implantation depth >25.5% emerged as independent predictors of PPMI. Upon modification of the implantation technique, aiming at a high final valve position, implantation depth decreased from 24% ventricular portion to 21% (p=0.012), accompanied by a decrease in PPMI rate (19.2% vs. 9.2%; p= 0.038). LVOTLC and LVOTRC calcium load, baseline right bundle branch block, and implantation depth were identified as independent predictors of the need for PPMI post-TAVR. Patient groups with different PPMI risk could bestratified using these 4 predictors. A slightly higher valve implantation site may prevent excessive PPMI rates.

Value of Genetic Testing for the Prediction of Long-Term Outcome in Patients With Hypertrophic Cardiomyopathy

Pathogenic gene mutations are found in about 50% of patients with hypertrophic cardiomyopathy (HC). Previous studies have shown an association between sarcomere mutations and medium-term outcome. The association with long-term outcome has not been described. The aim of this cohort study was to assess the long-term outcomes of patients with genotype positive (G+) and genotype negative (G-) HC. The study population consisted of 626 patients with HC (512 probands and 114 relatives) who underwent phenotyping and genetic testing from 1985 to 2014. End points were all-cause mortality, cardiovascular (CV) mortality, heart failure (HF)-related mortality, and sudden cardiac death/aborted sudden cardiac death (SCD/aborted SCD). Kaplan-Meier and multivariate Cox regression analyses were performed. A pathogenic mutation was detected in 327 patients (52%). G+ probands were younger than G- probands (46 ± 15 vs 55 ± 15years, p <0.001), had more non sustained ventricular tachycardia (34% vs 13%; p <0.001), more often a history of syncope (14% vs 7%; p= 0.016), and more extreme hypertrophy (maximal wall thickness ≥30mm, 7% vs 1%; p <0.001). G- probands were more symptomatic (New York Heart Association ≥II, 73% vs 53%, p <0.001) and had higher left ventricular outflow tract gradients (42 ± 39 vs 29 ± 33mm Hg, p= 0.001). During 12 ± 9years of follow-up, G+ status was an independent risk factor for all-cause mortality (hazard ratio [HR] 1.90, 95% CI 1.14 to 3.15; p= 0.014), CV mortality (HR 2.82, 95% CI 1.49 to 5.36; p= 0.002), HF-related mortality (HR 6.33, 95% CI 1.79 to 22.41; p= 0.004), and SCD/aborted SCD (HR 2.88, 95% CI 1.23 to 6.71; p= 0.015). In conclusion, during long-term follow-up, patients with G+ HC are at increased risk of all-cause death, CV death, HF-related death, and SCD/aborted SCD.

First Experience With Percutaneous Mitral Valve Plication as Primary Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy

BackgroundFew therapeutic options exist for patients with severe heart failure due to obstructive hypertrophic cardiomyopathy (HCM) who are at unacceptable surgical risk. We hypothesized that percutaneous plication of the mitral valve could reduce left ventricular outflow tract (LVOT) obstruction and associated mitral regurgitation, thereby leading to amelioration of heart failure symptoms. ObjectivesThis study sought to evaluate the potential effectiveness of percutaneous mitral valve plication as a therapy for patients with symptomatic, obstructive HCM. MethodsSix patients (age 83 ± 8 years; 5 women), judged as not optimal candidates for septal myectomy, were referred for management of severe, drug-refractory heart failure symptoms due to obstructive HCM (New York Heart Association functional class III). Each underwent percutaneous mitral valve leaflet plication to reduce systolic anterior motion (SAM) and mitral regurgitation using the transcatheter mitral clip system. ResultsThe procedure was completed in 5 patients with placement of a single clip at the A2-P2 segments of the mitral valve. One other patient experienced cardiac tamponade, leading to termination of the procedure. Among the 5 treated patients, percutaneous plication with the eliminated SAM and consequently decreased the intraoperative LVOT gradient (91 ± 44 mm Hg to 12 ± 6 mm Hg; p = 0.007), left atrial pressure (29 ± 11 mm Hg to 20 ± 8 mm Hg; p = 0.06), and mitral regurgitation grade (3.0 ± 0 vs. 0.8 ± 0.4; p = 0.0002) associated with improved cardiac output (in n = 4; 3.0 ± 0.6 l/min to 4.3 ± 1.2 l/min; p = 0.03). Over follow-up of 15 ± 4 months, symptom improvement to New York Heart Association functional class I or II occurred in all patients. Follow-up echocardiography after 15 ± 4 months demonstrated continued absence of SAM and significant reduction in mitral regurgitation, although high systolic LVOT velocities (i.e., >4 m/s) were evident in 3 of the 5 treated patients. ConclusionsThis is a report of percutaneous mitral valve plication as a primary therapy in the management of severely symptomatic, obstructive HCM patients. This initial experience suggests that percutaneous mitral valve plication may be effective for symptom relief in such patients via reduction of SAM and mitral regurgitation. The significance of persistent elevations of LVOT velocities in some patients requires further study.