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Current methods for predicting adverse events in patients with hypertrophic cardiomyopathy are still limited. Left ventricular global longitudinal strain (GLS) and left atrial volume index (LAVI) have been recently proposed as novel prognostic factors in several cardiovascular diseases. The objective of this study was to evaluate the prognostic value of GLS and LAVI in patients with hypertrophic cardiomyopathy.Two-dimensional echocardiography was performed in 427 patients with hypertrophic cardiomyopathy (66% men, age 52±15 years), and LAVI and GLS were assessed. During follow-up, the primary end point of all-cause mortality, heart transplantation, sudden cardiac death, and appropriate implantable cardioverter defibrillator therapy was noted. A total of 103 patients reached the primary end point during a follow-up of 6.7 (interquartile range, 3.3–10.0) years. Multivariable Cox regression analysis revealed GLS and LAVI to be independently associated with the primary end point (hazard ratio GLS, 1.10 [1.03–1.19], P=0.007; hazard ratio LAVI, 4.27 [2.35–7.74], P<0.001) after correcting for other clinical variables. When applying the pre-specified cut-off values of 34 mL/m2 for LAVI and −15% for GLS, Kaplan–Meier survival curves showed significant better survival for patients with LAVI <34 mL/m2 (P<0.001) and GLS <−15% (P<0.001) as compared with their counterparts. The likelihood ratio test showed a significant incremental prognostic value of LAVI and GLS (P<0.001) as compared with a model with clinical and standard echocardiographic risk factors. The C-statistic for this model increased from 0.68 to 0.73 when adding GLS and LAVI.GLS and LAVI are independently associated with adverse outcome in patients with hypertrophic cardiomyopathy and may help to optimize risk stratification in these patients.