Cardiac Remodeling in Subclinical Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial.

Importance: Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a subclinical stage who could benefit from therapies that prevent disease progression. Objective: To explore the potential for valsartan to modify disease development, and to characterize short-term phenotypic progression in subclinical HCM. Design, Setting, and Participants: The multicenter, double-blind, placebo-controlled Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) randomized clinical trial was conducted from April 2014 to July 2019 at 17 sites in 4 countries (Brazil, Canada, Denmark, and the US), with 2 years of follow-up. The prespecified exploratory VANISH cohort studied here included sarcomere variant carriers with subclinical HCM and early phenotypic manifestations (reduced E' velocity, electrocardiographic abnormalities, or an increased left ventricular [LV] wall thickness [LVWT] to cavity diameter ratio) but no LV hypertrophy (LVH). Data were analyzed between March and December 2022. Interventions: Treatment with placebo or valsartan (80 mg/d for children weighing <35 kg, 160 mg/d for children weighing ≥35 kg, or 320 mg/d for adults aged ≥18 years). Main Outcomes and Measures: The primary outcome was a composite z score incorporating changes in 9 parameters of cardiac remodeling (LV cavity volume, LVWT, and LV mass; left atrial [LA] volume; E' velocity and S' velocity; and serum troponin and N-terminal prohormone of brain natriuretic peptide levels). Results: This study included 34 participants, with a mean (SD) age of 16 (5) years (all were White). A total of 18 participants (8 female [44%] and 10 male [56%]) were randomized to valsartan and 16 (9 female [56%] and 7 male [44%]) were randomized to placebo. No statistically significant effects of valsartan on cardiac remodeling were detected (mean change in composite z score compared with placebo: -0.01 [95% CI, -0.29 to 0.26]; P = .92). Overall, 2-year phenotypic progression was modest, with only a mild increase in LA volume detected (increased by 3.5 mL/m2 [95% CI, 1.4-6.0 mL/m2]; P = .002). Nine participants (26%) had increased LVWT, including 6 (18%) who developed clinically overt HCM. Baseline LA volume index (LAVI; 35 vs 28 mL/m2; P = .01) and average interventricular septum thickness (8.5 vs 7.0 mm; P = .009) were higher in participants who developed HCM. Conclusions and Relevance: In this exploratory cohort, valsartan was not proven to slow progression of subclinical HCM. Minimal changes in markers of cardiac remodeling were observed, although nearly one-fifth of patients developed clinically overt HCM. Transition to disease was associated with greater baseline interventricular septum thickness and LAVI. These findings highlight the importance of following sarcomere variant carriers longitudinally and the critical need to improve understanding of factors that drive disease penetrance and progression. Trial Registration: ClinicalTrials.gov Identifier: NCT01912534.

A data-driven quality-score system for rating drug products and its implications for the health care industry.

The quality of drug products in the United States has been a matter of growing concern. Buyers and payers of pharmaceuticals have limited insight into measures of drug-product quality. Therefore, a quality-score system driven by data collection is proposed to differentiate between the qualities of drug products produced by different manufacturers. The quality scores derived using this proposed system would be based upon public regulatory data and independently-derived chemical data. A workflow for integrating the system into procurement decisions within health care organizations is also suggested. The implementation of such a quality-score system would benefit health care organizations by including the consideration of the quality of products while also considering price as a part of the drug procurement process. Such a system would also benefit the U.S. health care industry by bringing accountability and transparency into the drug supply chain and incentivizing manufacturers to place an increased emphasis on the quality and safety of their drug products.

Ventricular Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy (Analysis Spanning 60 Years Of Practice): AJC Expert Panel.

Surgical myectomy remains the time-honored primary treatment for hypertrophic cardiomyopathy patients with drug refractory limiting symptoms due to LV outflow obstruction. Based on >50 years experience, surgery reliably reverses disabling heart failure by permanently abolishing mechanical outflow impedance and mitral regurgitation, with normalization of LV pressures and preserved systolic function. A consortium of 10 international currently active myectomy centers report about 11,000 operations, increasing significantly in number over the most recent 15 years. Performed in experienced multidisciplinary institutions, perioperative mortality for myectomy has declined to 0.6%, becoming one of the safest currently performed open-heart procedures. Extended myectomy relieves symptoms in >90% of patients by ≥ 1 NYHA functional class, returning most to normal daily activity, and also with a long-term survival benefit; concomitant Cox-Maze procedure can reduce the number of atrial fibrillation episodes. Surgery, preferably performed in high volume clinical environments, continues to flourish as a guideline-based and preferred high benefit: low treatment risk option for adults and children with drug refractory disabling symptoms from obstruction, despite prior challenges: higher operative mortality/skepticism in 1960s/1970s; dual-chamber pacing in 1990s, alcohol ablation in 2000s, and now introduction of novel negative inotropic drugs potentially useful for symptom management.

Prognostic value of age-sex adjusted NT-proBNP ratio in obstructive hypertrophic cardiomyopathy.

BACKGROUND: We sought to determine the incremental prognostic value of age-sex adjusted N-terminal prohormone brain natriuretic peptide (NT-pro BNP) ratio in obstructive hypertrophic cardiomyopathy (oHCM) patients. METHODS: The study included 2119 consecutive oHCM patients (age 55 ± 13 years, 53% men, maximal LVOT ≥30 mmHg) evaluated between 6/2002-12/2018 with BNP or NT-pro BNP measured at baseline. NT-pro BNP ratio was calculated as: NT-proBNP/ upper limit of normal NT-proBNP derived from age-sex matched controls. Septal reduction therapy (SRT) during follow-up was recorded. Primary endpoint was death, need for cardiac transplantation or appropriate internal cardioverter defibrillator (ICD) discharge. RESULTS: Median NT-proBNP ratio was 5.4 (IQR 2.1-12.3). Using spline analysis, log-transformed NT-pro BNP ratio of 2 (corresponding to NT-pro BNP ratio of 6) was the optimal value where primary endpoint hazards crossed 1; there were 966 patients with high and 1153 patients with low NT-pro BNP ratio. 1665 (79%) patients underwent SRT at 47 days (IQR 7-128 days). At 5.4 years of follow-up (IQR 2.8-9.2 years), the primary outcome occurred in 315 (15%) patients (deaths = 270). High NT-pro BNP ratio was associated with higher risk of primary outcome in unadjusted (30.1 vs. 17.2 events/1000 person-year, hazard ratio or (HR) 1.73, 1.37-2.17, P < 0.001) and adjusted analysis (aHR 1.69, 95% 1.19-2.38, P = 0.003) vs. low NT-pro BNP ratio. Even in asymptomatic patients, NT-pro BNP ratio remained associated with primary outcome (aHR 1.28, 95% CI 1.06-1.54, P = 0.01). CONCLUSIONS: Age-sex adjusted NT-pro BNP ratio is independently associated with long-term outcomes in oHCM patients, including in a subgroup of asymptomatic patients.

Impact of left atrial strain mechanics on exercise intolerance and need for septal reduction therapy in hypertrophic cardiomyopathy.

AIMS: We sought to assess the relationship between left atrial (LA) strain mechanics and exercise intolerance, and to evaluate the prognostic impact of LA strain mechanics on clinical deterioration necessitating septal reduction therapy in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Consecutive HCM patients who underwent exercise stress echocardiography and cardiopulmonary exercise testing on the same day between October 2015 and April 2019 were enrolled prospectively. LA strain mechanics were analysed using speckle tracking echocardiography. LA stiffness was calculated as the ratio of E/e' ratio to LA reservoir strain. The study cohort was divided into four groups based on the quartile of percent-predicted peak VO2, and exercise intolerance was defined as the lowest quartile (≤51%). Of 532 patients studied (mean age: 51 ± 15 years, 42% female), 138 patients demonstrated exercise intolerance. As exercise capacity worsened, LA strain mechanics worsened along a continuum (P < 0.001). LA contractile strain with a cut-off of -13.9% was optimal at identifying exercise intolerance. On multivariable analysis, worse LA contractile strain was an independent predictor for exercise intolerance (P = 0.002). Of patients with left ventricular outflow tract obstruction, patients with LA stiffness worse than the median value (≥0.41) were significantly more likely to require septal reduction therapy than those with better LA stiffness (P = 0.026). CONCLUSION: Worse LA contractile strain was an independent predictor for exercise intolerance in HCM. Patients with worse LA stiffness had a higher probability of clinical deterioration necessitating septal reduction therapy.

Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial.

Hypertrophic cardiomyopathy (HCM) is often caused by pathogenic variants in sarcomeric genes and characterized by left ventricular (LV) hypertrophy, myocardial fibrosis and increased risk of heart failure and arrhythmias. There are no existing therapies to modify disease progression. In this study, we conducted a multi-center, double-blind, placebo-controlled phase 2 clinical trial to assess the safety and efficacy of the angiotensin II receptor blocker valsartan in attenuating disease evolution in early HCM. In total, 178 participants with early-stage sarcomeric HCM were randomized (1:1) to receive valsartan (320 mg daily in adults; 80-160 mg daily in children) or placebo for 2 years ( NCT01912534 ). Standardized changes from baseline to year 2 in LV wall thickness, mass and volumes; left atrial volume; tissue Doppler diastolic and systolic velocities; and serum levels of high-sensitivity troponin T and N-terminal pro-B-type natriuretic protein were integrated into a single composite z-score as the primary outcome. Valsartan (n = 88) improved cardiac structure and function compared to placebo (n = 90), as reflected by an increase in the composite z-score (between-group difference +0.231, 95% confidence interval (+0.098, +0.364); P = 0.001), which met the primary endpoint of the study. Treatment was well-tolerated. These results indicate a key opportunity to attenuate disease progression in early-stage sarcomeric HCM with an accessible and safe medication.

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

Background Hypertrophic cardiomyopathy (HCM) and aortic stenosis can cause obstruction to the flow of blood out of the left ventricular outflow tract into the aorta, with obstructive HCM resulting in dynamic left ventricular outflow tract obstruction and moderate or severe aortic stenosis causing fixed obstruction caused by calcific degeneration. We sought to report the characteristics and longer-term outcomes of patients with severe obstructive HCM who also had concomitant moderate or severe aortic stenosis requiring surgical myectomy and aortic valve replacement. Methods and Results We studied 191 consecutive patients (age 67±6 years, 52% men) who underwent myectomy and aortic valve (AV) replacement (90% bioprosthesis) at our center between June 2002 and June 2018. Clinical and echo data including left ventricular outflow tract gradient and indexed AV area were recorded. The primary outcome was death. Prevalence of hypertension (63%) and hyperlipidemia (75%) were high, with a Society of Thoracic Surgeons score of 5±4, and 70% of participants had no HCM-related sudden death risk factors. Basal septal thickness and indexed AV area were 1.9±0.4 cm and 0.72±0.2 cm2/m2, respectively, while 100% of patients had dynamic left ventricular outflow tract gradient >50 mm Hg. At 6.5±4 years, 52 (27%) patients died (1.5% in-hospital deaths). One-, 2-, and 5-year survival in the current study sample was 94%, 91%, and 83%, respectively, similar to an age-sex-matched general US population. On multivariate Cox survival analysis, age (hazard ratio [HR], 1.65; 95% CI, 1.24-2.18), chronic kidney disease (HR, 1.58; 95% CI, 1.21-2.32), and right ventricular systolic pressure on preoperative echocardiography (HR, 1.28; 95% CI, 1.05-1.57) were associated with longer-term mortality, but traditional HCM risk factors did not. Conclusions In symptomatic patients with severely obstructive HCM and moderate or severe aortic stenosis undergoing a combined surgical myectomy and AV replacement at our center, the observed postoperative mortality was significantly lower than the expected mortality, and the longer-term survival was similar to a normal age-sex-matched US population.

Characteristics and Outcomes of Elderly Patients With Hypertrophic Cardiomyopathy.

Background We report characteristics and outcomes of elderly patients with hypertrophic cardiomyopathy (HCM) with basal septal hypertrophy and dynamic left ventricular outflow tract obstruction. Methods and Results We 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%). Conclusions Elderly 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.

Background In 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 Results We 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). Conclusions In 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.

Characteristics and Longer-Term Outcomes of Contemporary Patients <18 Years of Age With Hypertrophic Cardiomyopathy.

We describe characteristics and outcomes of contemporary pediatric hypertrophic cardiomyopathy (PHC) patients. We studied 398 consecutive pediatric HC patients (<18 years, median 14 years, 65% boys) seen at our center between 2002 and 2018. Baseline clinical and pediatric echocardiographic data was collected. Left ventricular outflow tract gradient (LVOTG), LV fractional shortening and Z-score for left ventricular (LV) wall thickness were calculated. Sudden cardiac death (SCD), appropriate internal defibrillator discharge (ICD), myectomy, and orthotopic heart transplant (OHT) were composite primary endpoint. A total of 133 (33%) had symptoms (71 [18%] dyspnea, 77 [19%] angina, and 19 [5%] syncope), 109 (27%) were on beta-blockers; 179 (45%) had family history of HC. A total of 146 (37%) underwent genetic testing (of which 91 (62%) were HC-gene positive). Basal septal LV thickness, septal LV z-score and fractional shortening were 1.2 ± 0.6 cm, 4.8 ± 5.6, and 42% ± 8, whereas 23% had extreme LV hypertrophy (z-score > 6) and 8% had LVOTG >30 mm Hg (range 0 to 139 mm Hg). At a median of 5.9 years (interquartile range 2.4, 9), there were 23 (6%) ICD's placed, and 47 (12%) primary composite events (9 [2%] deaths, 3 [1%] appropriate ICD discharge, 29 [7%] myectomy, and 8 [2%] OHT). There were no in hospital deaths following myectomy/OHT. Presence of symptoms (Hazard ratio or HR 2.45), ventricular tachycardia (HR 1.52), and higher basal septal LV z-score (HR 1.10) were independently associated with primary composite outcomes. LV septal z-score >4 was independently associated with events on spline analysis. Rate of SCD/appropriate ICD discharge was 0.5%/year. In conclusion, contemporary PHC patients seen at an experienced center have excellent outcomes with presence of symptoms and higher LV septal thickness associated with primary composite events.

A Physician's Perspective on Generic Drug Quality.

DISCLOSURES: No funding supported the writing of this article. The author has nothing to disclose.

Prognostic Value of Global Longitudinal Strain in Hypertrophic Cardiomyopathy: A Systematic Review of Existing Literature.

OBJECTIVES: The association of left ventricular global longitudinal strain (LV-GLS) with clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) has been examined in multiple studies. The authors conducted a systematic review aimed at summarizing and critically appraising the current evidence. BACKGROUND: HCM is a common genetic cardiovascular disease with an estimated prevalence of 1 in 500 patients. LV-GLS derived from speckle tracking echocardiography is a sensitive noninvasive method of assessing regional left ventricular function. Several studies have suggested association of abnormal LV-GLS with outcomes in HCM patients. METHODS: A computerized literature search of all English language publications in the PubMed and EMBASE databases was made looking at all randomized and nonrandomized studies conducted on patients with HCM where association of LV-GLS with clinical outcomes was studied. We then manually searched the reference lists of included articles. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA) of reporting systematic reviews was used. RESULTS: Our search yielded a total of 14 observational studies published between 2009 and 2017 with a total of 3,154 patients with HCM. Eleven of the 14 studies included a composite cardiac outcome which included mortality as their primary outcome of interest and 3 of the 14 studies looked at association of LV-GLS with ventricular arrhythmias and/or implantable cardiac defibrillator discharge. We noted wide variability in inclusion, methodology, follow-up, and consequently effect estimates, which was not conducive to performing a meta-analysis. However, despite the variation, all studies revealed a degree of association of abnormal LV-GLS with poor cardiac outcomes. CONCLUSIONS: Our systematic review of more than 3000 HCM patients suggests an association of abnormal LV-GLS with adverse composite cardiac outcomes and ventricular arrhythmias.

Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and Preserved Systolic Function.

BACKGROUND: A high proportion of patients with hypertrophic cardiomyopathy (HCM) have evidence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). OBJECTIVES: This study sought to assess the incremental prognostic utility of LGE in patients with HCM. METHODS: We studied 1,423 consecutive low-/intermediate-risk patients with HCM (age ≥18 years) with preserved left ventricular (LV) ejection fraction (mean age 66 ± 14 years, 60% men) who underwent transthoracic echocardiography (TTE) (including dimensions and LV outflow tract gradients) and CMR (including LGE as a % of LV mass) at our center between January 2008 and December 2015. The primary composite endpoint was sudden cardiac death (SCD) and appropriate implantable cardioverter-defibrillator discharge. The percent 5-year SCD risk score was calculated. RESULTS: The mean 5-year SCD risk score was 2.3 ± 2.0. Mean maximal LV outflow tract gradient (TTE) was 70 ± 55 mm Hg (median 74 mm Hg [interquartile range (IQR): 10 to 67 mm Hg]); indexed LV mass and LGE (both on CMR) were 91 ± 10 g/m2 and 8.4 ± 12% (IQR: 0% to 19%); 50% had LGE on CMR. Of these, 458 were nonobstructive and 965 were obstructive (of which 686 were underwent myectomy). At 4.7 ± 2.0 years of follow-up, 60 (4%) met the composite endpoint. On quadratic spline analysis, LGE ≥15% was associated with increased risk of composite events. In the obstructive subgroup, on competing risk regression analysis, ≥15% LGE (subhazard ratio: 3.04 [95% confidence interval: 1.48 to 6.10]) was associated with a higher rate and myectomy (subhazard ratio: 0.44 [95% confidence interval: 0.20 to 0.76]) was associated with a lower rate of composite endpoints (both p < 0.01). Similarly, sequential addition of LGE ≥15% and myectomy to % 5-year SCD risk score improved the log likelihood ratios from -227.85 to -219.14 (chi-square 17) and to -215.14 (chi-square 8; both p < 0.01). Association of %LGE with composite events was similar even in myectomy and nonobstructive subgroups. CONCLUSIONS: In low-/intermediate-risk adult patients with HCM (obstructive, myectomy, and nonobstructive subgroups) with preserved systolic function, %LGE was significantly associated with a higher rate of composite endpoint, providing incremental prognostic utility.

Prediction of sudden death risk in obstructive hypertrophic cardiomyopathy: Potential for refinement of current criteria.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), the use of an implantable cardioverter defibrillator (ICD) can prevent sudden cardiac death (SCD). In patients with obstructive HCM, we sought to determine the prognostic utility of European Society of Cardiology (ESC) SCD risk score and to evaluate whether additional factors modulate SCD risk. METHODS: We studied 1809 consecutive patients with obstructive HCM (mean age, 50 ± 14 years; 63% males; mean maximal outflow tract gradient, 93 ± 40 mm Hg). Major SCD risk factors were recorded (0, 1, or ≥2) and % 5-year ESC SCD risk score was calculated. The need for surgical myectomy and a composite endpoint (SCD and/or appropriate ICD discharge) were recorded. RESULTS: The distribution of major SCD risk factors was 0 in 65% of the patients, 1 in 26%, and ≥2 in 8%. The 5-year ESC risk was low (<4%) in 65% of the patients, intermediate (4%-6%) in 18%, and high (>6%) in 17%. Surgery was performed in 1160 patients (64%), and 361 (20%) had AF. At a mean of 8.8 ± 4 years, 169 patients had a composite event (154 SCDs). At 5 years, despite a wide range of expected events (2.5%-9%), the observed events ranged from 4.6% to 5% across 3 SCD risk categories (Hosmer-Lemeshow P = .32). On multivariable competing-risk analysis, myectomy (subdistribution hazard ratio [sHR], 0.69; 95% confidence interval [CI], 0.47-0.83) was associated with lower risk of longer-term composite events (P < .01), whereas ESC SCD risk score was not (sHR, 1.31; 95% CI, 0.75-2.25; P = .36). CONCLUSIONS: In patients with obstructive HCM, despite a wide range of expected 5-year primary event rate, the observed primary events were similar across the 3 ESC SCD risk categories, with myectomy mitigating SCD risk. In patients with obstructive HCM, SCD risk may need to be refined for patients following myectomy.

Incremental Prognostic Utility of Left Ventricular Global Longitudinal Strain in Hypertrophic Obstructive Cardiomyopathy Patients and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: In obstructive hypertrophic cardiomyopathy patients with preserved left ventricular (LV) ejection fraction, we sought to determine whether LV global longitudinal strain (LV-GLS) provided incremental prognostic utility. METHODS AND RESULTS: We studied 1019 patients with documented hypertrophic cardiomyopathy (mean age, 50±12 years; 63% men) evaluated at our center between 2001 and 2011. We excluded age <18 years, maximal LV outflow tract gradient <30 mm Hg, bundle branch block or atrial fibrillation, past pacemaker/cardiac surgery, including myectomy/alcohol ablation, and obstructive coronary artery disease. Average resting LV-GLS was measured offline on 2-, 3-, 4-chamber views using Velocity Vector Imaging (Siemens, Malvern, PA). Outcome was a composite of cardiac death and appropriate internal defibrillator (implantable cardioverter defibrillator) discharge. Maximal LV thickness, LV ejection fraction, indexed left atrial dimension, rest and maximal LV outflow tract gradient, and LV-GLS were 2.0±0.2 cm, 62±4%, 2.2±4 cm/m2, 52±42 mm Hg, 103±36 mm Hg, and -13.6±4%. During 9.4±3 years of follow-up, 668 (66%), 166 (16%), and 122 (20%), respectively, had myectomy, atrial fibrillation, and implantable cardioverter defibrillator implantation, whereas 69 (7%) had composite events (62 cardiac deaths). Multivariable competing risk regression analysis revealed that higher age (subhazard ratio, 1.04 [1.02-1.07]), AF during follow-up (subhazard ratio, 1.39 [1.11-1.69]), and worsening LV-GLS (subhazard ratio, 1.11 [1.05-1.22]) were associated with worse outcomes, whereas myectomy (subhazard ratio, 0.44 [0.25-0.72]) was associated with improved outcomes (all P<0.01). Sixty-one percent of events occurred in patients with LV-GLS worse than median (-13.7%). CONCLUSIONS: In obstructive hypertrophic cardiomyopathy patients with preserved LV ejection fraction, abnormal LV-GLS was independently associated with higher events, whereas myectomy was associated with improved outcomes.

A Comprehensive Review of Stress Testing in Hypertrophic Cardiomyopathy: Assessment of Functional Capacity, Identification of Prognostic Indicators, and Detection of Coronary Artery Disease.

Hypertrophic cardiomyopathy is a heterogeneous condition that may present with functional limitation due to dyspnea on exertion, angina, or symptoms of heart failure. Although angina is a common symptom, it is thought to be multifactorial, including abnormal microvasculature and epicardial coronary artery disease. The role of stress testing in the detection of coronary artery disease and its limitations are discussed in this review. Stress testing yields additional information beyond the detection of ischemia, which is prognostic independent of the presence of coronary artery disease and can be beneficial in defining the presence of provocable left ventricular outflow tract obstruction, symptoms, response of heart rate and blood pressure to exercise, and functional capacity. Additional noninvasive imaging techniques, including speckle-tracking echocardiography and coronary flow velocity reserve, positron emission tomographic myocardial blood flow, delayed enhancement on cardiac magnetic resonance imaging, and computed tomographic angiography, are also discussed.

Comparison of Ventricular Septal Measurements in Hypertrophic Cardiomyopathy Patients Who Underwent Surgical Myectomy Using Multimodality Imaging and Implications for Diagnosis and Management.

Accurate and reproducible quantification of ventricular septal (VS) thickness in hypertrophic cardiomyopathy (HC) is essential for diagnosis, surgical planning, and risk stratification. We sought to compare VS thickness measurements using transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and cardiac magnetic resonance (CMR) in patients with HC. Prospectively reported measurements of VS thickness were compared using analysis of variance and Bland-Altman plots in 90 consecutive patients with HC who underwent a TTE, TEE, and CMR within 3 months. A subset was re-measured on 2 separate occasions by 2 readers to assess inter- and intraobserver variability. There was modest correlation between modalities, with CMR and TTE measurements of VS thickness showing the greatest correlation (CMR vs TTE, r = 0.70; CMR vs TEE, r = 0.60; TTE vs TEE, r = 0.56). Smaller measurements were seen using CMR versus either echocardiographic technique (13% smaller vs TEE, 8% smaller vs TTE, p <0.001 for both). The variability of measurement between modalities was not correlated with the degree of VS thickness. There was significantly lower intraobserver variability with CMR versus echocardiography (p = 0.01 for both), but no difference in interobserver variability. CMR delineated a different area of maximal VS thickness other than the basal anteroseptum more frequently than echocardiography (44% of cases vs 24% for TTE and 11% for TEE). In conclusion, CMR assessment of VS thickness differs significantly from echocardiography in patients with HC, with a systemic bias toward lower measurements seen with CMR.