Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers

AIMS: Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers. METHODS AND RESULTS: We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF ≥45% with normal LVMD ≤45 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF ≥45% with abnormal LVMD >45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF <45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)]. CONCLUSION: LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction

The effects of golimumab treatment on systolic and diastolic left ventricular function in ankylosing spondylitis

SC Heslinga,1,2 TC Konings,3 IE van der Horst-Bruinsma,1,2 O Kamp,3 VP van Halm,3,4 HACM de Bruin-Bon,4 MJ Peters,5 MT Nurmohamed1,2 1Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands; 2Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands; 3Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands; 4Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands; 5Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands Background: Diastolic left ventricular (LV) dysfunction appears more prevalent in ankylosing spondylitis (AS). The effects of tumor necrosis factor alpha (TNF-&alpha;) blocking therapy, a strong and effective anti-inflammatory drug, on diastolic LV function in AS are unknown. The objective of the study was to find the effects of 1-year treatment with golimumab 50 mg subcutaneously once per month on systolic and diastolic LV dysfunction in AS patients.Methods: Forty consecutive AS patients were treated with TNF-&alpha; blocking therapy for 1 year. Transthoracic echocardiography was performed in all patients at baseline and after 1 year of treatment.Results: Diastolic LV function improved after treatment in four out of six (67%) AS patients who completed follow-up (P=0.125), and did not develop or worsen in any of the other patients. Treatment with TNF-&alpha; blocking therapy had no effect on systolic LV function.Conclusion: These findings give support to the hypothesis that diastolic LV dysfunction improves during treatment with TNF-&alpha; blocking therapy. Keywords: ankylosing spondylitis, cardiovascular disease, anti-TN