Maximal Left Ventricular Outflow Tract Research Articles

AFFECT-HCM: quality of life and costs in hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, characterised by increased wall thickness. Pathogenic DNA variants in sarcomeric genes are identified in about half of HCM patients, enabling pre-symptomatic testing in family members. Since the first description of HCM tremendous progress has been made in the evaluation and management of HCM patients. However, little is known on the impact of HCM on quality of life (QoL) and costs. Purpose The AFFECT-HCM study evaluates the QoL, healthcare and societal costs in HCM patients and genotype-positive phenotype-negative (G+/P-) subjects. Methods The AFFECT-HCM is a multi-centre prospective study including genotyped HCM patients aged 18-80 years and G+/P- subjects. The study cohort is divided into three groups based on phenotype: G+/P- (wall thickness <13 mm), non-obstructive HCM (nHCM, maximal left ventricular outflow tract (LVOT) gradient <30 mmHg) and obstructive HCM (oHCM, LVOT gradient ≥30 mmHg). For QoL, the generic five-domain five-level EQ-5D-5L with the attached visual analogue scale and disease-specific Kansas City Cardiomyopathy Questionnaire are used. Healthcare and societal costs are measured via a bottom-up approach using the cost questionnaires iMCQ and iPCQ and expressed with means (the standard in healthcare cost reporting despite non-normality) in 2023 Euro per patient per year (€ PPPY). QoL and costs are compared between phenotypes. Results Results are summarised in the table. Between November 2022 - December 2023, 506 subjects (mean age 55 years, 39% female) were included in three Dutch hospitals. The study included 84 G+/P-, 307 nHCM and 115 oHCM subjects. Questionnaire response rate was 92%. Compared to G+/P- subjects; HCM patients were older (57 vs 46 yrs), more often male (67% vs 32%) and had more cardiovascular risk factors. Compared to nHCM patients, oHCM patients were more often symptomatic (58% vs 34%), more often in NYHA class III (19% vs 2%) and used more HCM-related medications (79% vs 64%). HCM patients, and particularly oHCM patients, reported decreased QoL with lower QoL-related questionnaire scores (Figure). The utilities (EQ-5D-5L) of HCM patients were lower than G+/P- subjects and the Dutch overall average (0.87±0.17), and for oHCM comparable with another study (0.82±0.18). Costs were higher for HCM patients than G+/P- subjects (€14374 vs €5888 PPPY) and higher in oHCM patients compared to nHCM patients (€19672 vs €12419 PPPY). The leading between-group difference is higher productivity losses in oHCM patients. Conclusion HCM is associated with reduced QoL and increased costs, especially in oHCM patients. The primary cost driver are healthcare costs, but the difference between oHCM and nHCM patients is mainly caused by indirect costs due to productivity losses. These data provide novel insights in the BoD of HCM and can aid in assessing cost-effectiveness analyses of new therapies for HCM in the future.Baseline characteristics and resultsQuality of life-related questionnaires

Long-Term Outcomes After Septal Reduction Therapies in Obstructive Hypertrophic Cardiomyopathy: Insights From the SHARE Registry.

Septal reduction therapy (SRT) provides substantial symptomatic improvement in patients with obstructive hypertrophic cardiomyopathy (HCM). However, long-term disease course after SRT and predictors of adverse outcomes have not been systematically examined. Data from 13 high clinical volume HCM centers from the international SHARE (Sarcomeric Human Cardiomyopathy Registry) were analyzed. Patients were followed from the time of SRT until last follow-up or occurrence of heart failure (HF) composite outcome (cardiac transplantation, implantation of a left ventricular assist device, left ventricular ejection fraction <35%, development of New York Heart Association class III or IV symptoms), ventricular arrhythmias composite outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter defibrillator therapy), or HCM-related death. Cox proportional hazards models were used to identify predictors of outcome. Of the 10 225 patients in SHARE, 1832 (18%; 968 [53%] male) underwent SRT, including 455 (25%) with alcohol septal ablation and 1377 (75%) with septal myectomy. The periprocedural 30-day mortality rate was 0.4% (8 of 1832) and 1499 of 1565 (92%) had a maximal left ventricular outflow tract gradient <50 mm Hg at 1 year. After 6.8 years (range, 3.4-9.8 years; 12 565 person-years) from SRT, 77 (4%) experienced HCM-related death (0.6% per year), 236 (13%) a composite HF outcome (1.9% per year), and 87 (5%) a composite ventricular arrhythmia outcome (0.7% per year). Among adults, older age at SRT was associated with a higher incidence of HCM death (hazard ratio, 1.22 [95 CI, 1.1-1.3]; P<0.01) and the HF composite (hazard ratio, 1.14 [95 CI, 1.1-1.2] per 5-year increase; P<0.01) in a multivariable model. Female patients also had a higher risk of the HF composite after SRT (hazard ratio, 1.4 [95 CI, 1.1-1.8]; P<0.01). De novo atrial fibrillation occurred after SRT in 387 patients (21%). Among pediatric patients followed for a median of 13 years after SRT, 26 of 343 (16%) developed the HF composite outcome, despite 96% being free of recurrent left ventricular outflow tract obstruction. Successful short- and long-term relief of outflow tract obstruction was observed in experienced multidisciplinary HCM centers. A subset of patients progressed to develop HF, but event-free survival at 10 years was 83% and ventricular arrhythmias were rare. Older age, female sex, and SRT during childhood were associated with a greater risk of developing HF.

Analysis of risk factors for complications in echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation

BackgroundThe feasibility of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) has been previously reported. However, limited investigation has been conducted regarding the complications associated with this procedure.ObjectiveThis study aims to analyze the risk factors affecting the occurrence of complications during PIMSRA, such as pericardial effusion, ventricular premature beats, and interventricular septal perforation. In this study, the optimal cut-off values for these risk factors are also explored, and corresponding strategies for prevention are proposed.MethodsA total of 101 patients diagnosed with HOCM who underwent the PIMSRA procedure from 2021 to 2022 were included in this retrospective analysis. Patients were classified into subgroups with or without complications based on procedural records. Univariate and multivariate regression analyses were conducted to identify independent risk factors for complications during the PIMSRA procedure.ResultsThere were 48 patients with complications and 53 patients without complications. The heart rate at the start of the procedure and the maximum left ventricular outflow tract gradient (LVOTG) were independent risk factors related to PIMSRA complications. The optimal cut-off values for predicting complication occurrence were a heart rate > 49 bpm at the start of the procedure (OR: 3.79, 95% CI: 1.64–8.78, p = 0.002) and a maximum LVOTG > 92 mmHg (OR: 2.57, 95% CI: 1.15–5.75, p = 0.022), respectively.ConclusionsThe occurrence of PIMSRA complications is primarily associated with the heart rate at the start of the procedure and the maximum LVOTG. It is recommended to establish a comprehensive control plan to minimize the risk of complications during PIMSRA procedures.

Transapical beating-heart septal myectomy for hypertrophic cardiomyopathy with latent obstruction.

A novel transapical beating-heart septal myectomy (TA-BSM) procedure was performed for patients with latent obstruction through the left intercostal incision and without cardiopulmonary bypass. This study aims to demonstrate the experience of the TA-BSM procedure for patients with latent obstruction and compare outcomes to patients with resting obstruction. We studied 120 symptomatic hypertrophic obstructive cardiomyopathy patients (33 with latent obstruction and 87 with resting obstruction) who underwent TA-BSM. Demographic profiles, echocardiogram-derived ventricular morphology and haemodynamics and clinical outcomes were analysed. There were no important differences in baseline clinical characteristics between patients with latent obstruction and resting obstruction, including age, symptoms, comorbidities and medical history. Patients with latent obstruction had lower basal septum thickness, higher midventricular wall thickness, smaller left atrial chamber size and more frequency of mitral subvalvular anomalies. There was no difference in early (<30 days) deaths (0/33 vs 1/87, P > 0.999) and mid-term survival between patients with latent obstruction and resting obstruction. At 6 months after surgery, 31 (93.9%) patients with latent obstruction and 80 (92.0%) with resting obstruction achieved optimal procedural success, which was defined as a maximal gradient (after provocation) <30 mmHg and mitral regurgitation ≤ grade 1+ without mortality. Maximal left ventricular outflow tract gradient, basal septum thickness, midventricular wall thickness, mitral regurgitation grade and left atrial chamber size were significantly decreased after TA-BSM. In the follow-up, the New York Heart Association class was significantly improved following surgery. TA-BSM preserved favourable gold-standard guideline desired outcomes through real-time echocardiographic-guided resection. Equipoise of outcomes for this procedure regardless of degree of resting left ventricular outflow tract gradients supports operative management with this approach in symptomatic patients with latent obstruction.

Effect of metoprolol in hypertrophic obstructive cardiomyopathy patients after alcohol septal ablation

BackgroundThe use of beta-blockers in hypertrophic obstructive cardiomyopathy (HOCM) patients after alcohol septal ablation (ASA) lacks data support. We aimed to evaluate the effect of metoprolol on exercise capacity, hemodynamic and laboratory parameters, and quality of life in HOCM patients after ASA. MethodsThis was a prospective randomized single-center open-label crossover trial in 21 HOCM patients after ASA. Patients received metoprolol and no beta-blocker for two periods of three months. The endpoints were: peak oxygen uptake (pVO2), maximal left ventricular outflow tract (LVOT) pressure gradient at peak exercise, a ratio of mitral peak velocity of the early filling (E) to early diastolic mitral annular velocity (e′) (E/e′) at rest, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) plasmatic concentration. ResultsNo significant association was found between the treatment and any of the endpoints in the assessed patients: 1) pVO2 (19.5 ± 5.3 ml/kg/min vs. 19.4 ± 4.1 ml/kg/min, p = 0.90), 2) exercise-induced pressure gradient in LVOT 32 ± 37 mmHg vs. 32 ± 30 mmHg, p = 0.84, 3) E/e′ ratio at rest (11 ± 4 vs. 10 ± 4, p = 0.23), 4) KCCQ overall summary score (78 ± 11 vs. 77 te ± 15, p = 0.56), 5) NT-proBNP (215 pg/ml [121–333] vs. 153 pg/ml [102–228], p = 0.19). ConclusionsIn HOCM patients after successful ASA, metoprolol treatment did not improve exercise capacity, hemodynamic and laboratory parameters, or quality of life.

Long-term outcomes of the classic Konno-Rastan procedure in paediatric and adult patients: impact of aortic annulus size on patient outcomes.

The classic Konno-Rastan procedure may yield different outcomes regarding aortic annulus diameters ≤15 mm and larger. Focusing on the effect of the diameter of the aortic annulus, we described the long-term outcomes of our patients. The outcomes of paediatric and adult patients who underwent surgery from 2000 to 2021 were studied retrospectively. The patient population was divided into 2 groups with aortic annulus diameters ≤15 mm and >15, and the outcomes were compared between the 2 groups. A total of 48 patients, with a mean age of 12.24 ± 9.42 years (2-53 years) and a median follow-up duration of 8 years (7 months to 20 years) with an IQR of 5.5, were enrolled. The mean peak instantaneous pressure gradient was 78.97 ± 25.29 mmHg, which decreased to 21.43 mmHg (P-value = 0.012). The maximum left ventricular outflow tract gradient at the last follow-up was 28.21 mmHg, with the exception of 1 case with a gradient of 68.45 mmHg. The mean diameter of the aortic annulus was 15.34 ± 3.87 mm (8-23 mm), and the mean prosthetic valve size was 20.31 mm, which was 5 mm (33%) larger than the native annulus diameter. The overall mortality rate was 6.3%, with 1 death in the hospital and 2 in the first year after the surgery. The major complication rate, including mortality, heart block and reintervention, was higher in patients with ≤15 mm annulus (P-value = 0.028.) However, there was no difference between the 2 groups in follow-up. Four (8%) late cardiac reoperations were performed, none of which were related to our surgeries. Kono-Rastan surgery for patients with aortic valve diameter of ≤15 mm can be performed with acceptable long-term outcomes.

First-in-Human Transapical Beating-Heart Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy

BackgroundTo simplify surgical septal reduction therapy for hypertrophic obstructive cardiomyopathy (HOCM), we developed a novel transapical beating-heart septal myectomy (TA-BSM) procedure. ObjectivesIn this study, we sought to evaluate the clinical utility of TA-BSM in a first-in-human trial. MethodsPatients with HOCM were enrolled if they presented with drug-refractory disabling symptoms. TA-BSM was performed via minithoracotomy with the use of our beating-heart myectomy device under echocardiographic guidance, without the use of cardiopulmonary bypass. Repeated resections were performed to tailor the extent of the septal myectomy for sufficient abolishment of left ventricular outflow tract (LVOT) obstruction and mitral regurgitation (MR). The primary outcome measure was procedural success, defined by resting/provoked LVOT gradient <30/50 mm Hg and residual MR grade ≤1+ (of 4+) at 3-month follow-up. ResultsA total of 47 patients aged 12 to 77 years were enrolled. Of the 46 patients who were followed for 3 months, 42 achieved procedural success. The maximal LVOT gradient decreased from 86 mm Hg (IQR: 67-114 mm Hg) at baseline to 19 mm Hg (IQR: 14-28 mm Hg) at 3 months. MR grade was ≤1+ in 3 patients at baseline and in 45 patients at 3 months. One patient died on postoperative day 10 owing to device-unrelated reasons. Other major adverse events included 1 delayed ventricular septal perforation and 1 intraoperative left ventricular apical tear. ConclusionsTA-BSM is a safe and efficient minimally invasive procedure for septal reduction of heterogeneous HOCM. Compared with conventional septal myectomy, TA-BSM provides real-time evaluation to guide resection while reducing surgical trauma. (Transapical Beating-Heart Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy; NCT05332691)

Septal Myectomy Outcomes in Children and Adolescents With Obstructive Hypertrophic Cardiomyopathy

BackgroundLittle data exist regarding characteristics and outcomes of pediatric patients undergoing septal myectomy. We evaluated this in a large referral population. MethodsSeptal myectomy was performed in 199 consecutive patients aged ≤18 years with obstructive hypertrophic cardiomyopathy from January 1, 1976, to June 30, 2021. ResultsMedian age was 13 years (interquartile range [IQR], 8-15 years). Left ventricular myectomy approaches included transaortic (163 of 198 [82%]), transapical (16 of 198 [8%]), and combined (19 of 198 [10%]). Right ventricular interventions included myectomy (13 of 199 [7%]) and patch reconstruction of the outflow tract (15 of 199 [8%]). Maximum left ventricular outflow tract gradients decreased after myectomy (prebypass: 50 mm Hg [IQR, 31-73 mm Hg] vs postbypass: 4 mm Hg [IQR, 0-9 mm Hg], P < .001), and this was sustained long-term (5 mm Hg [IQR, 5-10 mm Hg] at 10 years). Iatrogenic aortic and mitral valve injuries occurred in 13 of 199 (7%) and 1 of 199 (1%), respectively; however, all were successfully repaired. Operative mortality was 2 of 199 (1%). The cumulative incidence of redo myectomy was low, at 5.8% at 5 and 8.3% at 10 years. Redo myectomy patients had higher maximum left ventricular outflow tract gradients on echocardiography at predischarge and 1 year and were younger at the index operation (8 years [IQR, 2.5-10 years] vs 13 years [IQR, 9-16 years], P < .001). Overall survival at 10 years was 90%, relative to 47% in a previously reported pediatric nonoperative cohort. ConclusionsPediatric septal myectomy provides safe, effective, and durable relief of ventricular outflow tract obstruction. Iatrogenic valve injury remains a low but nonnegligible risk. Recurrent obstruction requiring redo myectomy is infrequent and can be identified early. Long-term survival in this pediatric septal myectomy cohort appears to fare better than pediatric hypertrophic cardiomyopathy cohorts managed nonoperatively.

Primeval outcomes of thoracoscopic transmitral myectomy with anterior mitral leaflet extension for hypertrophic obstructive cardiomyopathy

The transaortic Morrow procedure is the current gold standard for hypertrophic obstructive cardiomyopathy (HOCM) patients who are resistant to maximum drug therapy. It is controversial whether concomitant mitral valve intervention is necessary. Only a few centers apply for concomitant anterior mitral leaflet extension with a bovine or autologous pericardial patch to further decrease systolic anterior motion. Our aim is to assess the primeval outcomes of thoracoscopic transmitral myectomy with anterior mitral leaflet extension (TTM-AMLE) in symptomatic HOCM patients. Between April 2019 and November 2020, 18 consecutive HOCM patients who underwent TTM-AMLE were enrolled in this study. Preoperative, postoperative, and follow-up outcomes were compared and statistically analyzed. The mean age was (50.17 ± 6.18) years and 10 (55.56%) were males. 18 (100%) patients had mitral regurgitation preoperatively, and they all successfully underwent TTM-AMLE with a median cardiopulmonary bypass and aortic cross-clamp time of 200.0 (150.8, 232.0), and 127.5 (116.0, 149.0) min, respectively. The median length of ICU stay was 2.7 (1.4, 5.2) days. The interventricular septum thickness was significantly reduced (from 18.03 ± 3.02 mm to 11.91 ± 1.66 mm, p < .001). There was no perioperative mortality, perforation of ventricular septum, or conversion to sternotomy observed. During a median follow-up of 18 months (IQR, 5-24 months), 1 (5.56%) patient had severe mitral regurgitation due to patch detachment and received reoperation. Moderate degree of mitral regurgitation and more than 50 mmHg in left ventricular outflow tract gradient were found in 2 (11.11%), and 1 (5.56%) patients, respectively. 1 (5.56%) patient who had second-degree atrioventricular block received permanent pacemaker implantation postoperatively. Overall, the maximum left ventricular outflow tract gradient (88.50 [59.50, 112.75] mmHg vs. 10.50 [7.00, 15.50] mmHg, p = .002), left ventricular outflow tract velocity (4.70 [3.86, 5.33] m/s vs. 1.60 [1.33, 1.95] m/s, p < .001) and the degree of mitral regurgitation (6.99 ± 4.47 cm2 vs. 2.22 ± 1.51 cm2 , p = .001) were significantly decreased, with a significant reduction in the proportion of systolic anterior motion (94.44% vs. 16.67%, p < .001). The TTM-AMLE is a safe and effective surgical approach for selected patients with HOCM. In our series, it provides excellent relief of left ventricular outflow tract obstruction, while significantly eliminating mitral regurgitation. The early outcomes of TTM-AMLE are satisfactory, but further studies and longer follow-ups are awaited.

Identification of heart failure with preserved ejection fraction helps risk stratification for hypertrophic cardiomyopathy

BackgroundHeart failure with preserved ejection fraction (HFpEF) is the dominant form of heart failure (HF). We here aimed to investigate the characteristics and prognosis of HFpEF in patients with hypertrophic cardiomyopathy (HCM).MethodsThis was a prospective cohort study and patients with HCM with available NT-proBNP results were enrolled. Patients were categorized into HFpEF [defined as LVEF ≥50%, with symptoms or signs of HF, and N-terminal pro-brain natriuretic peptide ≥800 pg/mL according to American Heart Association (AHA) criteria] and without heart failure (non-HF). The outcomes of interest were all-cause death, cardiovascular death, and sudden cardiac death (SCD).ResultsOf 1178 included patients with HCM, 513 (43.5%) were identified as having HFpEF according to AHA criteria. Compared with non-HF patients, patients with HFpEF had significantly larger maximal wall thickness (P < 0.001), higher maximal left ventricular outflow tract gradient (P < 0.001), higher proportion of atrial fibrillation (P < 0.001), higher incidence of all-cause death (log-rank test, P = 0.002), and cardiovascular death (log-rank test, P = 0.005). Multivariable Cox analysis showed that patients with HFpEF had a nearly two-fold higher risk of all-cause death (adjusted HR = 1.80, 95% CI 1.11–2.90; P = 0.017) and cardiovascular death (adjusted HR =1.82, 95% CI 1.05–3.18; P = 0.033) than non-HF patients.ConclusionsPatients with HCM have a high prevalence of HFpEF and those with HFpEF present greater disease severity and higher mortality than non-HF patients, and thus may require an appropriate and more aggressive treatment for HF management. Identification of patients with HFpEF using AHA criteria can provide guidance on patient risk stratification for patients with HCM.

Perinatal and cardiac outcomes of women with hypertrophic cardiomyopathy

Rationale Pregnancy causes important physiologic stress for women with hypertrophic cardiomyopathy. Data regarding the impact of this condition on obstetrical outcomes is missing. Objectives Our objective was to report obstetrical and cardiac outcomes in pregnant women with hypertrophic cardiomyopathy and to assess the possible adverse effects of left ventricular outflow tract obstruction in pregnancy. Study design This was a retrospective cohort study of pregnant women diagnosed with HCM and followed at single tertiary center between 1995 and 2019. Demographic, medical and surgical data, echocardiographic parameters, and pregnancy outcomes were abstracted through extensive chart review. Patients were divided into 2 groups: obstructive (maximal left ventricular outflow tract gradient over 30 mmHg) versus non-obstructive hypertrophic cardiomyopathy. Outcomes between groups were compared with t-test, Mann-Whitney and Fisher’s exact tests when appropriate. Results Eighteen women with 27 pregnancies were included. The study population was formed of 18 women with a total of 27 pregnancies that reached at least 20 weeks of gestation: 12 pregnancies in women with obstructive hypertrophic cardiomyopathy and 15 pregnancies in women with non-obstructive hypertrophic cardiomyopathy. Among the non-obstructive hypertrophic cardiomyopathy, 5 of them had been treated for their obstruction. One patient with obstructive hypertrophic cardiomyopathy had a medical termination of pregnancy for uncontrolled arrhythmia at 21 weeks. There were no maternal deaths. Left ventricular outflow tract obstruction was associated with increased cardiac events including arrhythmias and heart failure (5/12 versus 0/15; p = .006). Preterm birth occurred in more than 50% of cases, resulting from induced delivery for a maternal (40%) or fetal reason (60%). Most deliveries were late preterm between 34 and 36 6/7 weeks. In both groups, birthweight was mainly distributed below the 50th percentile (89%) and 35% of neonates were born small for gestational age defined as a birthweight below the 10th percentile. Most severe cases of small for gestational age (birthweight under the 5th percentile) were found in patients with treated obstructive hypertrophic cardiomyopathy. Conclusion Hypertrophic cardiomyopathy is associated with prematurity and small for gestational age. Left ventricular outflow tract obstruction is associated with adverse cardiac events including arrythmias or heart failure. Treated obstructive cardiomyopathy constitutes a sub-group of patients at high risk of severe small for gestational age and deserves a close surveillance. Therefore, fetal growth surveillance with ultrasound, early in the third trimester and doppler studies to assess the utero-placental perfusion in the second and third trimesters are warranted in all patients with hypertrophic cardiomyopathy regardless of the severity of their condition.

Predictive value of NT-proBNP in non-obstructive hypertrophic cardiomyopathy

Abstract Background We studied the prognostic value of serum NT-proBNP in nonobstructive hypertrophic cardiomyopathy (nHCM) patients. Methods We studied 777 nHCM patients (55±13 years, 54% men, maximal left ventricular outflow tract gradient [LVOTG] &amp;lt;30 mm Hg) with serum NT-proBNP measured at baseline. We excluded patients with prior septal myectomy (SM) &amp; LV ejection fraction (LVEF) &amp;lt;55%. NT-proBNP was adjusted for age &amp; sex &amp; converted to a log NT-proBNP ratio. Clinical &amp; echo variables were recorded. Primary endpoint was death, appropriate implantable defibrillator (ICD) discharge or heart transplant. Results NT-proBNP ratio was high in 473 and low in 304 patients. Median [interquartile range] LVEF, LVOTG &amp; NT-proBNP were 61% [59, 66], 7 [4, 12] mm Hg &amp; 481 [137–1361] pg/dl. 31% had functional class ≥II &amp; 32% had ≥1 sudden cardiac death risk factor. At 5.3 [3–9] years, 139 (18%) met the primary endpoint (107 deaths). On spline analysis, log NT-proBNP ratio &amp;gt;2.75 was associated with higher events. Cox &amp; Kaplan-Meier survival analyses showed that high NT-proBNP ratio was independently associated with events (Figures 1A-B). In the subgroup of asymptomatic patients, NT-proBNP ratio remained associated with the primary outcome (adjusted HR 1.45, 95% CI 1.10–1.93, P=0.009). Conclusions Higher NT-proBNP ratio (&amp;gt;2.75) is independently associated with adverse outcomes in nHCM, including asymptomatic patients, suggesting risk stratification even in earlier disease stages. Funding Acknowledgement Type of funding sources: None.

Surgical Septal Myectomy for the Treatment of Residual Left Ventricular Outflow Tract Obstruction Following Failed Alcohol Septal Ablation.

The reasons of residual left ventricular outflow tract (LVOT) obstruction following alcohol septal ablation (ASA) remain unclear, and outcomes of myectomy following failed ASA remain underreported.Thirteen symptomatic patients (10 women, a median age of 60.0 years) who underwent septal myectomy following failed ASA were reviewed. The patients were followed up for a median of 6 months. The clinical characteristics and outcomes of these patients were analyzed and were compared with those of 178 patients who underwent isolated myectomy without previous ASA at our institution during the same period.In the first ASA procedure, the median number of septal perforator arteries injected was 1.0 with the median value of peak creatine kinase following ablation of 978.5 U/L.Uncontrollable extent and location of infarcted myocardium caused by ablation and mitral subvalvular anomalies were found in four (30.8%) and seven (53.8%) patients, respectively. No operative or follow-up deaths occurred. The median maximum LVOT gradients fell from preoperative 112.0 to 8.5 mmHg at follow-up (P < 0.001). Compared with controls, patients with failed ASA had a higher proportion of mitral subvalvular anomalies (53.8% versus 13.5%, P = 0.001) and developed a higher incidence of complete atrioventricular block following myectomy (15.4% versus 1.7%, P = 0.038).Low institutional or operator experience with ablation, uncontrollable extent and location of infarcted myocardium caused by ablation, and mitral subvalvular anomalies may be reasons for failed ASA. Surgical myectomy for the treatment of residual LVOT obstruction after unsuccessful ASA may be associated with favorable results.

Characteristics and Outcomes of Elderly Patients With Hypertrophic Cardiomyopathy.

BackgroundWe report characteristics and outcomes of elderly patients with hypertrophic cardiomyopathy (HCM) with basal septal hypertrophy and dynamic left ventricular outflow tract obstruction.Methods and ResultsWe studied 1110 consecutive elderly patients with HCM (excluding moderate or greater aortic stenosis or subaortic membrane, age 80±5 years [range, 75–92 years], 66% women), evaluated at our center between June 2002 and December 2018. Clinical and echocardiographic data, including maximal left ventricular outflow tract gradient, were recorded. The primary outcome was death and appropriate internal defibrillator discharge. Hypertension was observed in 72%, with a Society of Thoracic Surgeons (STS) score (8.6±6); while 80% had no HCM‐related sudden cardiac death risk factors. Left ventricular mass index, basal septal thickness, and maximal left ventricular outflow tract gradient were 127±43 g/m2, 1.7±0.4 cm, and 49±31 mm Hg, respectively. A total of 597 (54%) had a left ventricular outflow tract gradient >30 mm Hg, of which 195 (33%) underwent septal reduction therapy (SRT; 79% myectomy and 21% alcohol ablation). At 5.1±4 years, 556 (50%) had composite events (273 [53%] in nonobstructive, 220 [55%] in obstructive without SRT, and 63 [32%] in obstructive subgroup with SRT). One‐ and 5‐year survival, respectively were 93% and 63% in nonobstructive, 90% and 63% in obstructive subgroup without SRT, and 94% and 84% in the obstructive subgroup with SRT. Following SRT, there were 5 (2.5%) in‐hospital deaths (versus an expected Society of Thoracic Surgeons mortality of 9.2%).ConclusionsElderly patients with HCM have a high prevalence of traditional cardiovascular rather than HCM risk factors. Longer‐term outcomes of the obstructive SRT subgroup were similar to a normal age‐sex matched US population.

Outcomes in Guideline-Based Class I Indication Versus Earlier Referral for Surgical Myectomy in Hypertrophic Obstructive Cardiomyopathy.

BackgroundIn patients with obstructive hypertrophic cardiomyopathy, surgical myectomy (SM) is indicated for severe symptoms. We sought to compare long‐term outcomes of patients with obstructive hypertrophic cardiomyopathy where SM was based on guideline‐recommended Class I indication (Functional Class or FC ≥3 or angina/exertional syncope despite maximal medical therapy) versus earlier (FC 2 and/or impaired exercise capacity on exercise echocardiography with severe obstruction).Methods and ResultsWe studied 2268 consecutive patients (excluding <18 years, ≥ moderate aortic stenosis and subaortic membrane, 56±14 years, 55% men), who underwent SM at our center between June 2002 and March 2018. Clinical data, including left ventricular outflow tract gradient, were recorded. Death and/or appropriate internal defibrillator discharge were primary composite end points. One thousand three hundred eighteen (58%) patients met Class I indication and 950 (42%) underwent earlier surgery; 222 (10%) had a history of obstructive coronary artery disease. Basal septal thickness, and resting and maximal left ventricular outflow tract gradient were 2.0±0.3 cm, 61±44 mm Hg, and 100±31 mm Hg, respectively. At 6.2±4 years after SM, 248 (11%) had composite events (13 [0.6%] in‐hospital deaths). Age (hazard ratio [HR], 1.61; 95% CI, 1.26–1.91), obstructive coronary artery disease (HR, 1.46; 95% CI, 1.06–1.91), and Class I versus earlier SM (HR, 1.61; 95% CI, 1.14–2.12) were associated with higher primary composite events (all P<0.001). Earlier surgery had better longer‐term survival (similar to age‐sex‐matched normal population) versus surgery for Class I indication (76 [8%] versus 193 [15%], P<0.001).ConclusionsIn patients with obstructive hypertrophic cardiomyopathy, earlier versus surgery for Class I indication had a better long‐term survival, similar to the age‐sex‐matched US population.

Edge-to-Edge Repair Versus Secondary Cord Cutting During Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy: A Pilot Randomised Study

To evaluate whether the Alfieri technique improves clinical and haemodynamic results and compare it with transaortic mitral valve secondary cord cutting in patients scheduled for septal myectomy for severely symptomatic hypertrophic obstructive cardiomyopathy. Forty-eight (48) patients with moderate-to-severe systolic anterior motion (SAM)-mediated mitral regurgitation were randomly assigned to the Alfieri or Cutting groups in addition to septal myectomy. The primary endpoint was postoperative mean transmitral pressure gradient (TPG). The secondary endpoints were residual left ventricular outflow tract (LVOT) gradient after procedure, residual mitral regurgitation (MR), postoperative SAM, repeating bypass, and survival. There were no 30-day mortality and ventricular septal defects. The postoperative LVOT gradient was 15.4±7.6 mmHg and 11.1±4.9 mmHg (p=0.078) in the Alfieri and Cutting groups, respectively. The Alfieri technique was associated with higher peak (7.8±3.3 vs 4.7±2.8 mmHg; p=0.014) and mean (3.9±1.7 vs 2.1±1.6 mmHg; p=0.013) TPG. The Cutting group was associated with higher mild MR rate at discharge (six vs no patients; p=0.009). One (1) patient (4.2%) in the Alfieri group required pacemaker implantation owing to conduction disturbances (p=0.312). Two-year (2-year) freedom from late mortality and sudden cardiac death rates were 95.5%±4.4% and 100% for the Alfieri and Cutting groups, respectively (log rank, p=0.317). No patients had New York Heart Association functional class III or IV or moderate or severe MR. The maximum LVOT gradient was 20.4±15.2 mmHg and 16.7±10.4 mmHg, respectively (p=0.330). There were no reoperations during follow-up. Both techniques with septal myectomy effectively eliminated SAM-induced MR and LVOT obstructions in hypertrophic cardiomyopathy patients.

Evaluation of N-terminal prohormone of brain natriuretic peptide and cardiac troponin-I levels in cats with systolic anterior motion of the mitral valve in the absence of left ventricular hypertrophy

ObjectivesTo identify the prevalence of systolic anterior motion of the mitral valve (SAM) in apparently healthy cats in the absence of left ventricular hypertrophy (LVH) and examine the relationship between specific cardiac biomarker concentrations and echocardiographic parameters in these individuals. Animalseighty client-owned cats. Materials and methodsretrospective study; inclusion criteria were the presence of SAM on conscious echocardiography and concurrent measurement of plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and serum cardiac troponin-I (cTnI). Cats were excluded if they had LVH, left atrial enlargement or systemic disease. The percentages of cats with NT-proBNP and cTnI concentrations above the normal reference range were calculated. The correlation between each biomarker concentration and left ventricular myocardial wall thickness, left atrial size and maximum left ventricular outflow tract velocity was evaluated. ResultsThirty-four of 80 patients with SAM showed no evidence of cardiac remodelling (LVH or left atrial enlargement). Of these patients, 30 of 34 had elevated NT-proBNP, and cTnI was elevated in 13 of 27 (48.1%) cats where this biomarker was measured in association with the NT-proBNP assay. A positive correlation was observed between concentration of plasma NT-proBNP and maximum left ventricular outflow tract velocity (rs = 0.67, p<0.0001). No significant correlations were found between the concentration of biomarkers and the remaining echocardiographic parameters. ConclusionsSAM is frequently observed in cats even in the absence of cardiac remodelling, and these individuals often demonstrate elevated plasma NT-proBNP and serum cTnI concentrations. Plasma NT-proBNP elevation is correlated with the severity of the left ventricular outflow obstruction caused by SAM.

Effect of Trimetazidine Dihydrochloride Therapy on Exercise Capacity in Patients With Nonobstructive Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy causes limiting symptoms in patients, mediated partly through inefficient myocardial energy use. There is conflicting evidence for therapy with inhibitors of myocardial fatty acid metabolism in patients with nonobstructive hypertrophic cardiomyopathy. To determine the effect of oral therapy with trimetazidine, a direct inhibitor of fatty acid β-oxidation, on exercise capacity in patients with symptomatic nonobstructive hypertrophic cardiomyopathy. This randomized, placebo-controlled, double-blind clinical trial at The Heart Hospital, University College London Hospitals, London, United Kingdom was performed between May 31, 2012, and September 8, 2014. The trial included 51 drug-refractory symptomatic (New York Heart Association class ≥2) patients aged 24 to 74 years with a maximum left ventricular outflow tract gradient 50 mm Hg or lower and a peak oxygen consumption during exercise of 80% or less predicted value for age and sex. Statistical analysis was performed from March 1, 2016 through July 4, 2018. Participants were randomly assigned to trimetazidine, 20 mg, 3 times daily (n = 27) or placebo (n = 24) for 3 months. The primary end point was peak oxygen consumption during upright bicycle ergometry. Secondary end points were 6-minute walk distance, quality of life (Minnesota Living with Heart Failure questionnaire), frequency of ventricular ectopic beats, diastolic function, serum N-terminal pro-brain natriuretic peptide level, and troponin T level. Of 49 participants who received trimetazidine (n = 26) or placebo (n = 23) and completed the study, 34 (70%) were male; the mean (SD) age was 50 (13) years. Trimetazidine therapy did not improve exercise capacity, with patients in the trimetazidine group walking 38.4 m (95% CI, 5.13 to 71.70 m) less than patients in the placebo group at 3 months after adjustment for their baseline walking distance measurements. After adjustment for baseline values, peak oxygen consumption was 1.35 mL/kg per minute lower (95% CI, -2.58 to -0.11 mL/kg per minute; P = .03) in the intervention group after 3 months. In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited. ClinicalTrials.gov identifier: NCT01696370.

Reduction of left ventricular mass, left atrial size, and N-terminal pro-B-type natriuretic peptide level following alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy.

Alcohol septal ablation (ASA) is an alternative to surgical treatment in patients with hypertrophic obstructive cardiomyopathy (HOCM). Through alcohol-induced necrosis, ASA leads to an increase in left ventricular outflow tract (LVOT) diameter and a decrease in LVOT pressure gradient. We sought to assess the effect of ASA on left ventricular (LV) wall thickness and mass, left atrial (LA) size, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. The study cohort consisted of 50 patients with HOCM (30 in the ASA group, 20 in the optimal pharmacotherapy group [OPG]). Transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and NT-proBNP level analysis were performed at baseline and at six months. All parameters are presented as means. In the ASA group, the maximal LVOT pressure gradient decreased from 122.7 to 54.8 mmHg directly after ASA and to 37.2 mmHg after a further six months (p < 0.0001). The NT-proBNP level decreased from 2174.4 to 1103.4 pg/mL (p < 0.001). On TTE, the interventricular septum (IVS) thickness decreased to from 23.6 to 19.4 mm (p < 0.0001) and the lateral wall (LW) thickness decreased from 15.9 to 14.2 mm (p < 0.007). On CMR, basal IVS thickness decreased from 23.7 to 18.0 mm (p < 0.0001) and the LW thickness decreased from 13.2 to 12.2 mm (p = 0.02). IVS mass reduced from 108.9 to 91.5 g (-16%; p < 0.001). All of the above parameters remained unchanged in the OPG. Successful ASA reduces LV hypertrophy and improves parameters of the LV overload, resulting in LV wall hy-pertrophy regression, and LA size and NT-proBNP level reduction. The above parameters may be as useful in assessing the efficacy of ASA as the LVOT gradient itself.

Clinical and prognostic impact of chronotropic incompetence in patients with hypertrophic cardiomyopathy

BackgroundA blunted heart rate (HR) response is associated with an impaired peak oxygen uptake (pVO2), a powerful outcome predictor in hypertrophic cardiomyopathy (HCM). The present multicenter study sought to determine the prognostic role for exercise-induced HR response in HCM. MethodsA total of 681 consecutive HCM outpatients on optimized treatment were recruited. The heart failure (HF) end-point was death due to HF, cardiac transplantation, NYHA III-IV class progression, HF worsening leading to hospitalization and severe functional deterioration leading to septal reduction. The sudden cardiac death (SCD) end-point included SCD, aborted SCD and appropriate implantable cardioverter defibrillator discharges. ResultsDuring a median follow-up of 4.2 years (25–75th centile: 3.9–5.2), 81 patients reached the HF and 23 the SCD end-point. Covariates with independent effects on the HF end-point were left atrial diameter, left ventricular ejection fraction, maximal left ventricular outflow tract gradient and exercise cardiac power (ECP = pVO2∗systolic blood pressure) (C-Index = 0.807) whereas the HCM Risk-SCD score and the ECP remained associated with the SCD end-point (C-Index = 0.674). When the VO2-derived variables were not pursued, peak HR (pHR) re-entered in the multivariate HF model (C-Index = 0.777) and, marginally, in the SCD model (C-index = 0.656). A pHR = 70% of the maximum predicted resulted as the best cut-off value in predicting the HF-related events. ConclusionsThe cardiopulmonary exercise test is pivotal in the HCM management, however the pHR remains a meaningful alternative parameter. A pHR < 70% identified a HCM population at high risk of HF-related events, thus calling for a reappraisal of the chronotropic incompetence threshold in HCM.