The prognostic impact of right ventricular-pulmonary arterial coupling in heart failure: a systematic review and meta-analysis.

The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling which corresponds well with the respective invasively derived index. Recently, a wealth of observational data has arisen, outlining its prognostic value in heart failure (HF) patients. To systematically appraise and quantitatively synthesize the evidence of the prognostic value of TAPSE/PASP ratio in left-sided HF regardless of etiology or left ventricular ejection fraction. A systematic literature review was conducted in electronic databases to identify studies reporting the association of TAPSE/PASP ratio with outcomes in patients with HF and, when appropriate, a random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome of all-cause death or HF hospitalization. Eighteen studies were deemed eligible encompassing 8,699 HF patients. The applied cut-off value for RV-PA uncoupling varied substantially from 0.27 to 0.58 mm/mmHg, and in most studies values lower than the applied cutoff conveyed dismal prognosis. Eleven studies reported appropriate data for meta-analysis. TAPSE/PASP reduction by 1 mm/mmHg was independently associated with all-cause death (pooled aHR=1.32 [1.06-1.65]; p=0.01; I2=56%) and the composite outcome (pooled aHR=3.48 [1.67-7.25]; p<0.001; I2=0%). When a TAPSE/PASP cutoff value of 0.36 mm/mmHg was applied it yielded independent association with all-cause death (pooled aHR=2.84 [2.22-3.64]; p<0.001; I2=82%). RV-PA coupling assessed by echocardiographic TAPSE/PASP ratio appears to be an independent outcome predictor for HF patients.

Prescription Rates and Prognostic Implications of Optimally Targeted Guideline-Directed Medical Treatment in Heart Failure and Atrial Fibrillation: Insights From The MISOAC-AF Trial.

ABSTRACT: Heart failure (HF) and atrial fibrillation (AF) commonly coexist in real-life clinical practice. Among patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF), guidelines call for evidence-based target doses of renin-angiotensin-aldosterone system inhibitors and beta-blockers. However, target doses of guideline-directed medical treatment (GDMT) are often underused in real-world conditions, including HF-AF comorbidity. This retrospective cohort study of a randomized trial (Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with nonvalvular AF) included hospitalized patients with AF and HFrEF or HFmrEF. Optimally targeted GDMT was defined as intake of evidence-based target doses of renin-angiotensin-aldosterone system and beta-blockers at 3 months after discharge. Rates of optimally targeted GDMT achievement across the baseline estimated glomerular filtration rate (eGFR) were assessed. Independent predictors of nontargeted GDMT and its association with all-cause mortality and the composite of cardiovascular death or HF hospitalization were assessed by regression analyses. In total, 374 patients with AF and HFrEF or HFmrEF were studied. At 3 months after discharge, 30.7% received target doses of GDMT medications. The rate of optimally targeted GDMT was reduced by 11% for every 10 mg/min/1.73 m 2 decrease in baseline eGFR [adjusted ß = 0.99; 95% confidence interval (CI), 0.98-0.99] levels. After a median 31-month follow-up period, 37.8% patients in the optimally targeted GDMT group died, as compared with 67.8% (adjusted hazard ratio: 1.49; 95% CI, 1.05-2.13) in the nontargeted GDMT group. The risk of cardiovascular death or HF hospitalization was also higher in these patients (adjusted hazard ratio: 1.60; 95% CI, 1.17-2.20). Target doses of all HF drugs were reached in roughly one-third of patients with AF and HFrEF or HFmrEF 3 months after hospital discharge. Nontargeted GDMT was more frequent across lower eGFR levels and was associated with worse outcomes.

Left Atrial Myopathy is Associated With Exercise Incapacity and Ventilatory Inefficiency in Hypertrophic Cardiomyopathy.

BACKGROUND: Left atrial (LA) myopathy is an established component of hypertrophic cardiomyopathy (HCM); however, the data about its association with exercise incapacity or ventilatory inefficiency that may be seen in HCM patients are limited. This study aimed to explore the association between LA myopathy, evaluated by echocardiography LA strain, and exercise capacity and ventilatory efficiency, evaluated by cardiopulmonary exercise testing (CPET), in HCM patients. METHODS: This study included 241 consecutive HCM patients (aged 51.2±15.7 years 67.2% male) in sinus rhythm who underwent CPET and transthoracic echocardiography at the same visit. Exercise incapacity (maximal/predicted oxygen consumption [%peakVO2] <80%) and ventilatory inefficiency (ventilation/carbon dioxide output [VE/VCO2] slope >34) were assessed by CPET. Left atrial myopathy was examined by speckle-tracking myocardial deformation parameters: LA reservoir, conduit and booster strain. RESULTS: All three LA strain values were univariate predictors of exercise capacity and ventilatory efficiency. Among them, LA reservoir strain had the higher r correlation coefficient for predicting both %peakVO2 and VE/VCO2 slope. Left atrial reservoir strain, presence of angina and family history of HCM were independent predictors of exercise capacity. Left atrial reservoir strain, male gender and non-sustained ventricular tachycardia were independent predictors of ventilatory efficiency. Left atrial reservoir strain was a significant predictor of %peakVO2<80% with an optimal cut-off value of 27% (sensitivity 87% and specificity 31%) and VE/VCO2>34 with an optimal cut-off value of 18% (sensitivity 71% and specificity 83%). CONCLUSION: Left atrial myopathy, as reflected by the LA strain values, was associated with exercise incapacity and ventilatory inefficiency in HCM individuals. Left atrial reservoir strain was the only common independent predictor of %peakVO2 and VE/VCO2 slope.

A critical approach for successful use of circulating microRNAs as biomarkers in cardiovascular diseases: the case of hypertrophic cardiomyopathy.

MicroRNAs (miRNAs) are small noncoding RNA molecules that act as major regulators of gene expression at the post-transcriptional level. As the potential applications of miRNAs in the diagnosis and treatment of human diseases have become more evident, many studies of hypertrophic cardiomyopathy (HCM) have focused on the systemic identification and quantification of miRNAs in biofluids and myocardial tissues. HCM is a hereditary cardiomyopathy caused by mutations in genes encoding proteins of the sarcomere. Despite overall improvements in survival, progression to heart failure, stroke, and sudden cardiac death remain prominent features of living with HCM. Several miRNAs have been shown to be promising biomarkers of HCM; however, there are many challenges to ensuring the validity, consistency, and reproducibility of these biomarkers for clinical use. In particular, miRNA testing may be limited by pre-analytical and analytical caveats, making our interpretation of results challenging. Such factors that may affect miRNA testing include sample type selection, hemolysis, platelet activation, and renal dysfunction. Therefore, researchers should be careful when developing appropriate standards for the design of miRNA profiling studies in order to ensure that all results provided are both accurate and reliable. In this review, we discuss the application of miRNAs as biomarkers for HCM.

Deciphering hypertrophic cardiomyopathy with electrocardiography.

The comprehensive assessment of patients with hypertrophic cardiomyopathy is a complex process, with each step concurrently focusing on confirmation of the diagnosis, differentiation between sarcomeric and non-sarcomeric disease (phenocopy), and prognostication. Novel modalities such as genetic testing and advanced imaging have allowed for substantial advancements in the understanding of this condition and facilitate patient management. However, their availability is at present not universal, and interpretation requires a high level of expertise. In this setting, electrocardiography, a fast and widely available method, still retains a significant role in everyday clinical assessment of this population. In our review, we follow a stepwise approach for the interpretation of each electrocardiographic segment, discussing clinical implications of electrocardiographic patterns in sarcomeric disease, their value in the differential diagnosis from phenocopies, and impact on patient management. Outlining the substantial amount of information to be obtained from a simple tracing, we exhibit how electrocardiography is likely to remain an integral diagnostic tool in the future as well.

Mitral regurgitation impact on left atrial myopathy in hypertrophic cardiomyopathy.

BACKGROUND: Recent studies have shown that mitral regurgitation (MR) represents a major determinant of left atrial (LA) function in patients with heart failure with preserved ejection fraction. The role of MR in determining LA myopathy in hypertrophic cardiomyopathy (HCM) is unknown. The aim of this study was to examine the association of MR with LA myopathy, assessed by LA strain values in HCM patients. METHODS: In total 250 consecutive patients (mean age 51 ± 16 years, 67.2% male) with an established diagnosis of HCM and with sinus rhythm at index echocardiography evaluation were included. LA reservoir, conduit and booster strain were analyzed, besides LA size, left ventricular (LV) systolic and diastolic function. The predictors of LA strain values were identified with linear regression analysis. RESULTS: Significant (more than mild) MR was a significant univariate predictor of all the three LA strain values. In multivariate linear regression analysis, independent predictors of LA reservoir strain were more than mild MR (r = -.23), LV global longitudinal strain (r = -.49), LA volume index (r = -.27) and patient age (r = -.23). Significant MR was also an independent determinant of LA conduit (r = -.17) and booster strain (r = -.12). In patients with LA volume index < 34 ml/m2 more than mild MR was an independent predictor of LA reservoir (r = -.32) and conduit strain (r = -.27), but not LA booster strain. CONCLUSION: Significant MR is associated with LA myopathy independently of the LV diastolic and systolic function and LA size.

A novel quantitative method for assessing the therapeutic response to Tafamidis therapy in patients with cardiac TTR amyloidosis. A preliminary report.

OBJECTIVE: Cardiomyopathy is a common manifestation of transthyretin amyloidosis (ATTR), leading to heart failure, associated with high morbidity and mortality. The aim of this study was to investigate the effect of Tafamidis treatment by means of cardiac radiotracer uptake on myocardial scintigraphy. SUBJECTS AND METHODS: Five male patients, mean age 76.2 years, with wild-type ATTR were included in the protocol. Total body scanning using technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) (in four patients) and technetium-99m-hydroxymethylene diphosphonate (99mTc-HMDP) (in one) was performed pre- and one year post-Tafamidis therapy. A novel quantitation method for assessing radiotracer cardiac uptake was employed. The geometric mean was computed for both cardiac and thigh region of interest (ROI) and the heart-to-thigh (HtT) ratio was assessed by dividing the corresponding geometric mean counts. RESULTS: Heart-to-thigh ratio was improved (decreased) in four of the patients receiving Tafamidis, in keeping with lower uptake to the cardiac region. These patients also demonstrated a relatively favorable clinical response to Tafamidis. The patient evaluated by 99mTc-HMDP exhibited minimal HtT ratio reduction and stable clinical and echocardiographic characteristics. CONCLUSION: Sequential HtT ratio measurements could potentially identify patients with a favorable response to Tafamidis treatment at earlier stages, compared to other imaging modalities or serological biomarkers.

Emerging concepts in arrhythmogenic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) represents one of the primary cardiomyopathies and may lead to heart failure and sudden death. Until recently, ventricular arrhythmias were considered to be a direct consequence of the systolic dysfunction of the left ventricle (LV) and guidelines for implantable cardioverter defibrillator implantation were established on this basis. However, the identification of heritable dilated cardiomyopathy phenotypes that presented with mildly impaired or moderate LV dysfunction, with or without chamber dilatation, and ventricular arrhythmias exceeding the degree of the underlying morphological abnormalities lead to the identification of the arrhythmogenic phenotypes and genotypes of DCM. This subset of DCM patients presents phenotypic and in many cases genotypic overlaps with left dominant arrhythmogenic cardiomyopathy (LDAC). LMNA, SCN5A, FLNC, TTN, and RBM20 are the main genes responsible for arrhythmogenic DCM. Moreover, desmosomal genes such as DSP and other non-desmosomal such as DES and PLN have been associated with both LDAC and arrhythmogenic DCM. The aim of this review is to highlight the importance of genetic profiling among DCM patients with disproportionate arrhythmic burden and the significance of the electrocardiogram, cardiac magnetic resonance, Holter monitoring, detailed family history, and other assays in order to identify red flags for arrhythmogenic DCM and proceed to an early preventive approach for sudden cardiac death. A special consideration was given to the phenotypic and genotypic overlap with LDAC. The role of myocarditis as a common disease expression of LDAC and arrhythmogenic DCM is also analyzed supporting the premise of their phenotypic overlap.

Practical recommendations for the diagnosis and management of transthyretin cardiac amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by accumulation in the heart interstitium of amyloid fibrils formed by misfolded proteins. Most common CA types are light chain amyloidosis (AL) caused by monoclonal immunoglobulin light chains and transthyretin amyloidosis (ATTR) caused by either mutated or wild-type transthyretin aggregates. Previously considered a rare disease, CA is increasingly recognized among patients who may be misdiagnosed as undifferentiated heart failure with preserved ejection fraction (HFPEF), paradoxical low-flow/low-gradient aortic stenosis, or otherwise unexplained left ventricular hypertrophy. Progress in diagnosis has been due to the refinement of cardiac echocardiographic techniques (speckle tracking imaging) and magnetic resonance (T1 mapping) and mostly due to the advent of bone scintigraphy that has enabled noninvasive diagnosis of ATTR, limiting the need for endomyocardial biopsy. Importantly, proper management of CA starts from early recognition of suspected cases among high prevalence populations, followed by advanced diagnostic evaluation to confirm diagnosis and typing, preferentially in experienced amyloidosis centers. Differentiating ATTR from other types of amyloidosis, especially AL, is critical. Emerging targeted ATTR therapies offer the potential to improve outcomes of these patients previously treated only palliatively.

Evaluation of mitral regurgitation by cardiac magnetic resonance and transthoracic echocardiography: a systematic review and meta-analysis.

Transthoracic echocardiography (TTE) and Cardiac Magnetic Resonance (CMR) have complementary roles in the severity grading of mitral regurgitation (MR). Our objective was to systematically review the correlation of MR severity as assessed by TTE and CMR. We searched MEDLINE and Cochrane Library for original series published between January 1st, 2000 and March 23rd, 2020. We used Cohen's kappa coefficient to measure agreement between modalities. We plotted a hierarchical summary receiver operator characteristic (HSROC) curve and estimated the area under the curve (AUC) to assess the concordance between the two imaging modalities for the detection of severe MR. We identified 858 studies, of which 65 underwent full-text assessment and 8 were included in the meta-analysis. A total of 718 patients were included (425 males, 59%) in the final analysis. There was significant heterogeneity in the methods used and considerable variation in kappa coefficient, ranging from 0.10 to 0.48. Seven out of eight studies provided the necessary data to plot HSROC curves and calculate the AUC. The AUC for detecting severe MR was 0.83 (95% CI 0.80 to 0.86), whereas the AUC for detecting moderate to severe MR was 0.83 (95% CI 0.79 to 0.86). The agreement between TTE and CMR in MR severity evaluation is modest across the entire spectrum of severity grading. However, when focusing on patients with at least moderate MR the concordance between TTE and CMR is very good. Further prospective studies comparing hard clinical endpoints based on the CMR and TTE assessment of MR severity are needed.

Prognostic implications of valvular heart disease in patients with non-valvular atrial fibrillation.

BACKGROUND: Valvular heart disease (VHD) in non-valvular atrial fibrillation (AF) is a puzzling clinical entity. The aim of this study was to evaluate the prognostic effect of significant VHD (sVHD) among patients with non-valvular AF. METHODS: This is a post-hoc analysis of the MISOAC-AF trial (NCT02941978). Consecutive inpatients with non-valvular AF who underwent echocardiography were included. sVHD was defined as the presence of at least moderate aortic stenosis (AS) or aortic/mitral/tricuspid regurgitation (AR/MR/TR). Cox regression analyses with covariate adjustments were used for outcome prediction. RESULTS: In total, 983 patients with non-valvular AF (median age 76 [14] years) were analyzed over a median follow-up period of 32 [20] months. sVHD was diagnosed in 575 (58.5%) AF patients. sVHD was associated with all-cause mortality (21.6%/yr vs. 6.5%/yr; adjusted HR [aHR] 1.55, 95% confidence interval [CI] 1.17-2.06; p = 0.02), cardiovascular mortality (16%/yr vs. 4%/yr; aHR 1.70, 95% CI 1.09-2.66; p = 0.02) and heart failure-hospitalization (5.8%/yr vs. 1.8%/yr; aHR 2.53, 95% CI 1.35-4.63; p = 0.02). The prognostic effect of sVHD was particularly evident in patients aged < 80 years and in those without history of heart failure (p for interaction < 0.05, in both subgroups). After multivariable adjustment, moderate/severe AS and TR were associated with mortality, while AS and MR with heart failure-hospitalization. CONCLUSION: Among patients with non-valvular AF, sVHD was highly prevalent and beared high prognostic value across a wide spectrum of clinical outcomes, especially in patients aged < 80 years or in the absence of heart failure. Predominantly AS, as well as MR and TR, were associated with worse prognosis.

An Overview of Pharmacotherapy in Hypertrophic Cardiomyopathy: Current Speculations and Clinical Perspectives.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Its clinical course is variable, ranging from a benign asymptomatic or mildly symptomatic course throughout life, to severe symptoms (dyspnea, angina, palpitations) or cardiovascular events (syncope and thromboembolism). Sudden cardiac death (SCD) remains the most striking manifestation of the disease, affecting a minority of patients. This review focuses on the medical treatments applied according to the symptomatology in obstructive and nonobstructive HCM; a special reference is made to atrial fibrillation and arterial hypertension, which often coexist with the disease. Current literature about the pharmaceutical prevention of SCD is also analyzed and novel pharmacologic agents and approaches that may represent the future management of HCM are critically reviewed. The analysis of interventional techniques that are used in cases of medical treatment failure is avoided. Rather than enumerating clinical studies and guidelines, this review provides a concise and contemporary analysis of HCM pharmacotherapy, developing applicable algorithms for clinicians and highlighting promising future drug regimens.

Multiorgan Congestion Assessment by Venous Excess Ultrasound Score in Acute Heart Failure.

BACKGROUND: This study sought to explore the prevalence and clinical utility of different patterns of multiorgan venous congestion as assessed by the venous excess ultrasound (VExUS) score in hospitalized patients with acute heart failure (HF). METHODS: Consecutive patients admitted for acute HF were prospectively enrolled. Inferior vena cava diameter, hepatic vein, portal vein, and renal vein Doppler waveforms were assessed at admission, and patients were stratified based on VExUS score from 0 to 3, with higher values indicating worse congestion. The clinical score Get with the Guidelines (GWTG)-HF for predicting in-hospital mortality in HF was evaluated. In-hospital mortality was recorded. RESULTS: Two hundred ninety patients admitted with acute HF were included, and 114 (39%) of them were classified as VExUS score 3, which was the most prevalent group. Patients with VExUS score 3 suffered more frequently from chronic atrial fibrillation, chronic kidney disease, and anemia. Parameters independently associated with VExUS score 3 were higher mean E/e' ratio, larger right ventricular size, severe tricuspid regurgitation, and impaired right atrial function. A VExUS score of 3 was associated with in-hospital mortality (odds ratio, 8.03; 95% CI [2.25-28.61], P = .001). The addition of VExUS score on top of the GWTG-HF score improved the predictability of the model (Δx2 = +8.44, P = .03) for in-hospital mortality, whereas other indices of venous congestion (right atrial function, inferior vena cava size) did not. CONCLUSIONS: Patients admitted with acute HF commonly had severe venous congestion based on the VExUS score. The VExUS score improved the prediction of in-hospital mortality compared with other indices of venous congestion.

Clinical characteristics and natural history of hypertrophic cardiomyopathy with midventricular obstruction.

BACKGROUND: The prevalence, clinical characteristics and natural history of patients with hypertrophic cardiomyopathy (HCM) and midventricular obstruction (MVO) have not been adequately studied. METHODS AND RESULTS: A single-center cohort consisting of 423 patients (mean age, 49.3±17.2 years; 66.2% male) was thoroughly followed up for a median of 84 months (7 years; range, 6-480 months). MVO, characterized by the echocardiographic appearance of midventricular muscular apposition with a simultaneous mid-cavitary gradient ≥30mmHg, was identified in 34 patients (8%). Patients with MVO tended to be more symptomatic during their initial evaluation (>90% presented with NYHA class ≥II) compared to the rest of the HCM cohort. Apical aneurysm formation was identified in more than one-fourth of patients with MVO (26.5%), being a characteristic of the group. On multivariate Cox regression hazard analysis, presence of MVO strongly predicted progression to end-stage (burnt out) HCM and related heart failure (HF) deaths (hazard ratio, [HR], 2.62; 95% confidence interval [CI]: 1.2-8.8; P=0.047), as well as sudden death and associated lethal arrhythmic events (HR, 3.3; 95% CI: 1.26-8.85; P=0.016). CONCLUSIONS: MVO is a distinct phenotype of HCM associated with unfavorable prognosis in terms of end-stage HCM, sudden death and lethal arrhythmic events. The high adverse outcome rate necessitates early recognition of MVO and appropriate therapeutic interventions.

Efficacy of various "classic" echocardiographic and laboratory indices in distinguishing the "gray zone" between athlete's heart and hypertrophic cardiomyopathy: a pilot study.

Left ventricular hypertrophy (LVH) with intraventricular septum thickness (IVST) between 1.2 and 1.5 cm in athletes represents a "gray zone" between physiologic adaptation and mild hypertrophic cardiomyopathy (HCM). Various echo and laboratory parameters have been reported till now in the literature to discriminate the "gray zone" entities. Aim of this study was to assess the efficacy of these "classic" parameters in differentiating physiologic LVH in athletes from mild HCM in a highly selected population. Nine highly trained athletes with IVST (1.28 ± 0.07 cm), 9 patients with mild HCM (1.38 ± 0.11 cm), and 26 athletes without LVH (1.06 ± 0.09 cm; P < 0.0005) underwent echocardiographic study, cardiopulmonary treadmill exercise stress test, and brain natriuretic peptide (BNP) measurement before and after exercise. Among all parameters tested, 7 were found to significantly differ between "gray zone" groups. After bootstrapping analysis, it was found that athletes with left ventricular end-diastolic diameter <4.74 cm, mitral deceleration time >200 ms, isovolumic relaxation time >94 ms, tricuspid E/A < 1.63, septum Em < 9.5 cm/sec, relative wall thickness >0.445, and a BNP value at rest >9.84 pg/mL had a greater possibility for having underlying cardiomyopathy. A 10-point score based on these parameters showed accuracy (area under the curve = 0.958 [95%CI: 0.738-1.0; P = 0.00005, standard error = 0.0342]) for revealing HCM in a gray zone athletic population. Differentiation of adaptive LVH versus HCM in a gray zone population could be facilitated by recognition of certain features referring to LV dimensions, diastolic function, and BNP.

Wild-Type Transthyretin Amyloid Cardiomyopathy: The Gordian-Knot of Novel Therapeutic Regimens.

Wild-type TTR amyloidosis (wtATTR) represents a disease difficult to diagnose with poor prognosis. Increased clinical suspicion is key, allowing for timely diagnosis. Until recently, only off-label therapies were available but recent introduction of disease specific therapy has shown potential to alter the natural history of the disease. Tafamidis, the only currently approved drug for the therapy of wtATTR, provided significantly better survival and quality of life. However, not all subgroups of patients derived equal benefit. This, along with the increased cost of treatment raised question on whether treatment should be invariably administered through the wtATTR population. This review aims to summarize current evidence on the natural history and staging systems for wtATTR, as well as available treatment options. Special consideration is given to the selection process of patients who would be expected to gain maximum benefit from tafamidis treatment, based on an ethical and cost-effective point of view.

Quantitative Late Gadolinium Enhancement Cardiac Magnetic Resonance and Sudden Death in Hypertrophic Cardiomyopathy: A Meta-Analysis.

BACKGROUND: Quantitative late gadolinium enhancement (LGE) cardiac magnetic resonance provides important prognostic information for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). However, it has not been fully integrated into clinical practice. OBJECTIVES: To assess the prognostic value of LGE extent in predicting SCD in adults with HCM across different methods of quantification, thresholds, and patients' clinical profile. METHODS: The authors searched PubMed, Web of Science, and Cochrane Library for studies investigating the prognostic value of LGE% in predicting SCD in HCM. Pooled odds ratios were calculated with 95% CIs. The optimal threshold was determined using a multiple cutoffs model. RESULTS: Eleven studies were included in the meta-analysis with a total of 5,550 patients and a median follow-up time of 5.2 years. Two studies quantified LGE manually, 7 studies used the 6 SD technique, 1 study used the 4 SD technique, and 1 study the 2 SD technique. There was no statistically significant difference in predicting SCD between these 4 methods (P = 0.443). Optimal cutoff could be determined only for the 6 SD technique. LGE 10% was the optimal threshold of the 6 SD technique with sensitivity 0.73 and specificity 0.67. CONCLUSIONS: The different LGE quantification techniques have comparable accuracy in predicting SCD. When the more extensively studied 6 SD technique is used, LGE 10% is the optimal cutoff and can effectively restratify intermediate-risk patients. LGE extent can improve HCM risk stratification, but it is unlikely to become a standalone tool.