Usefulness of Left Atrial Emptying Fraction to Predict Ventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillators
2017; Elsevier BV; Volume: 120; Issue: 2 Linguagem: Inglês
10.1016/j.amjcard.2017.04.015
ISSN1879-1913
AutoresMischa T. Rijnierse, Mehran Sadeghian, Sophie Schuurmans Stekhoven, P. Stefan Biesbroek, Anne‐Lotte C.J. van der Lingen, Peter M. van de Ven, Albert C. van Rossum, Robin Nijveldt, Cornelis P. Allaart,
Tópico(s)Cardiac Imaging and Diagnostics
ResumoImpaired left atrial emptying fraction (LAEF) is an important predictor of mortality in patients with heart failure. As it may reflect increased LV wall stress, it might predict ventricular arrhythmia (VA) specifically. This study evaluated the predictive value of LAEF assessed with cardiovascular magnetic resonance (CMR) imaging with respect to appropriate device therapy (ADT) for VA and compared its role with CMR assessed scar size and other risk factors. In total, 229 patients (68% male, 63 ± 10 years, 61% ischemic cardiomyopathy) with LV ejection fraction ≤35% who underwent CMR and implantable cardioverter defibrillator (ICD) implantation for primary prevention in 2005 to 2012 were included. CMR was used to quantify LV volumes and function. LV scar size was quantified when late gadolinium enhancement was available (n = 166). Maximum and minimum left atrial volumes and LAEF were calculated using the biplane area-length method. The occurrence of ADT and mortality was assessed during a median follow-up of 3.9 years. Sixty-two patients (27%) received ADT. Univariable Cox analysis showed that male gender, creatinine level, minimum left atrial volume, LAEF, and total scar size were significant predictors of ADT. In multivariable Cox analysis, LAEF (hazard ratio 0.75 per 10%, p median and scar size < median were at low risk (13% ADT at 5 years), whereas those with LAEF < median and scar size > median experienced 40% ADT at 5 years (log-rank p = 0.01). In conclusion, LAEF independently predicts ADT in patients with primary prevention ICDs. Combined assessment of LAEF and scar size identifies a group with low risk of ADT. Therefore, LAEF assessment could assist in risk stratification for VA to select patients with the highest benefit from ICD implantation. Impaired left atrial emptying fraction (LAEF) is an important predictor of mortality in patients with heart failure. As it may reflect increased LV wall stress, it might predict ventricular arrhythmia (VA) specifically. This study evaluated the predictive value of LAEF assessed with cardiovascular magnetic resonance (CMR) imaging with respect to appropriate device therapy (ADT) for VA and compared its role with CMR assessed scar size and other risk factors. In total, 229 patients (68% male, 63 ± 10 years, 61% ischemic cardiomyopathy) with LV ejection fraction ≤35% who underwent CMR and implantable cardioverter defibrillator (ICD) implantation for primary prevention in 2005 to 2012 were included. CMR was used to quantify LV volumes and function. LV scar size was quantified when late gadolinium enhancement was available (n = 166). Maximum and minimum left atrial volumes and LAEF were calculated using the biplane area-length method. The occurrence of ADT and mortality was assessed during a median follow-up of 3.9 years. Sixty-two patients (27%) received ADT. Univariable Cox analysis showed that male gender, creatinine level, minimum left atrial volume, LAEF, and total scar size were significant predictors of ADT. In multivariable Cox analysis, LAEF (hazard ratio 0.75 per 10%, p median and scar size < median were at low risk (13% ADT at 5 years), whereas those with LAEF < median and scar size > median experienced 40% ADT at 5 years (log-rank p = 0.01). In conclusion, LAEF independently predicts ADT in patients with primary prevention ICDs. Combined assessment of LAEF and scar size identifies a group with low risk of ADT. Therefore, LAEF assessment could assist in risk stratification for VA to select patients with the highest benefit from ICD implantation. The implantable cardioverter defibrillator (ICD) implantation is the first choice therapy in patients with heart failure and left ventricular ejection fraction (LVEF) ≤35% for the primary prevention of sudden cardiac death (SCD).1Zipes D.P. Camm A.J. Borggrefe M. Buxton A.E. Chaitman B. Fromer M. Gregoratos G. Klein G. Moss A.J. Myerburg R.J. Priori S.G. Quinones M.A. Roden D.M. Silka M.J. Tracy C. Smith Jr., S.C. Jacobs A.K. Adams C.D. Antman E.M. Anderson J.L. Hunt S.A. Halperin J.L. Nishimura R. Ornato J.P. Page R.L. Riegel B. Blanc J.J. Budaj A. Dean V. Deckers J.W. Despres C. Dickstein K. Lekakis J. McGregor K. Metra M. Morais J. Osterspey A. Tamargo J.L. Zamorano J.L. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for practice guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.Circulation. 2006; 114: e385-e484Crossref PubMed Scopus (994) Google Scholar However, follow-up studies report an ICD discharge rate of only 9% to 35% after 30 to 36 months in patients treated with ICDs for primary prevention.2Sabbag A. Suleiman M. Laish-Farkash A. Samania N. Kazatsker M. Goldenberg I. Glikson M. Beinart R. Contemporary rates of appropriate shock therapy in patients who receive implantable device therapy in a real-world setting: from the Israeli ICD Registry.Heart Rhythm. 2015; 12: 2426-2433Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 3Moss A.J. Greenberg H. Case R.B. Zareba W. Hall W.J. Brown M.W. Daubert J.P. McNitt S. Andrews M.L. Elkin A.D. Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator.Circulation. 2004; 110: 3760-3765Crossref PubMed Scopus (493) Google Scholar Enhanced risk prediction of ventricular arrhythmia (VA) beyond LVEF assessment, therefore, is needed. Previous studies have demonstrated that enlarged left atrial (LA) volumes (LAVs) and impaired LA emptying fraction (LAEF) predict the risk of heart failure progression and mortality.4Gulati A. Ismail T.F. Jabbour A. Ismail N.A. Morarji K. Ali A. Raza S. Khwaja J. Brown T.D. Liodakis E. Baksi A.J. Shakur R. Guha K. Roughton M. Wage R. Cook S.A. Alpendurada F. Assomull R.G. Mohiaddin R.H. Cowie M.R. Pennell D.J. Prasad S.K. Clinical utility and prognostic value of left atrial volume assessment by cardiovascular magnetic resonance in non-ischaemic dilated cardiomyopathy.Eur J Heart Fail. 2013; 15: 660-670Crossref PubMed Scopus (78) Google Scholar, 5Gupta S. Matulevicius S.A. Ayers C.R. Berry J.D. Patel P.C. Markham D.W. Levine B.D. Chin K.M. de Lemos J.A. Peshock R.M. Drazner M.H. Left atrial structure and function and clinical outcomes in the general population.Eur Heart J. 2013; 34: 278-285Crossref PubMed Scopus (163) Google Scholar, 6Pellicori P. Zhang J. Lukaschuk E. Joseph A.C. Bourantas C.V. Loh H. Bragadeesh T. Clark A.L. Cleland J.G. Left atrial function measured by cardiac magnetic resonance imaging in patients with heart failure: clinical associations and prognostic value.Eur Heart J. 2015; 36: 733-742Crossref PubMed Scopus (95) Google Scholar, 7Rossi A. Temporelli P.L. Quintana M. Dini F.L. Ghio S. Hillis G.S. Klein A.L. Marsan N.A. Prior D.L. Yu C.M. Poppe K.K. Doughty R.N. Whalley G.A. Independent relationship of left atrial size and mortality in patients with heart failure: an individual patient meta-analysis of longitudinal data (MeRGE Heart Failure).Eur J Heart Fail. 2009; 11: 929-936Crossref PubMed Scopus (125) Google Scholar As the prognosis in patients with heart failure is partially driven by SCD, markers of LA dysfunction may also relate to VA in particular. Impaired LA function might reflect increased LV filling pressure and wall stress which may contribute to the formation of fatal arrhythmias due to modulation of action potential duration, calcium handling, and conduction.8Tomaselli G.F. Zipes D.P. What causes sudden death in heart failure?.Circ Res. 2004; 95: 754-763Crossref PubMed Scopus (461) Google Scholar, 9Nuss H.B. Kaab S. Kass D.A. Tomaselli G.F. Marban E. Cellular basis of ventricular arrhythmias and abnormal automaticity in heart failure.Am J Physiol. 1999; 277: H80-H91PubMed Google Scholar, 10Hoit B.D. Left atrial size and function: role in prognosis.J Am Coll Cardiol. 2014; 63: 493-505Crossref PubMed Scopus (581) Google Scholar, 11Calkins H. Maughan W.L. Weisman H.F. Sugiura S. Sagawa K. Levine J.H. Effect of acute volume load on refractoriness and arrhythmia development in isolated, chronically infarcted canine hearts.Circulation. 1989; 79: 687-697Crossref PubMed Scopus (116) Google Scholar Data on the value of markers for LA dysfunction in predicting VA, however, are lacking. Using cardiovascular magnetic resonance (CMR) imaging, LA volumes and function can be accurately evaluated. In addition, LV scar tissue, which is known to be associated with the occurrence of VA, can be quantified.12Perazzolo M.M. De L.M. Zorzi A. Migliore F. Zilio F. Calore C. Vettor G. Tona F. Tarantini G. Cacciavillani L. Corbetti F. Giorgi B. Miotto D. Thiene G. Basso C. Iliceto S. Corrado D. Impact of the presence and amount of myocardial fibrosis by cardiac magnetic resonance on arrhythmic outcome and sudden cardiac death in nonischemic dilated cardiomyopathy.Heart Rhythm. 2014; 11: 856-863Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 13Klem I. Weinsaft J.W. Bahnson T.D. Hegland D. Kim H.W. Hayes B. Parker M.A. Judd R.M. Kim R.J. Assessment of myocardial scarring improves risk stratification in patients evaluated for cardiac defibrillator implantation.J Am Coll Cardiol. 2012; 60: 408-420Crossref PubMed Scopus (244) Google Scholar, 14de Haan S. Meijers T.A. Knaapen P. Beek A.M. van Rossum A.C. Allaart C.P. Scar size and characteristics assessed by CMR predict ventricular arrhythmias in ischaemic cardiomyopathy: comparison of previously validated models.Heart. 2011; 97: 1951-1956Crossref PubMed Scopus (86) Google Scholar This study aimed to evaluate the predictive value of LA function with respect to appropriate device therapy (ADT) for VA and to compare its role with scar size and other risk factors. This study included consecutive patients with ischemic and dilated cardiomyopathy (ICMP and DCMP) and LVEF ≤35% who received an ICD for primary prevention of SCD according to the American College of Cardiology/American Heart Association/European Society of Cardiology 2006 guidelines from January 2005 to December 2012 in the VU University Medical Center.1Zipes D.P. Camm A.J. Borggrefe M. Buxton A.E. Chaitman B. Fromer M. Gregoratos G. Klein G. Moss A.J. Myerburg R.J. Priori S.G. Quinones M.A. Roden D.M. Silka M.J. Tracy C. Smith Jr., S.C. Jacobs A.K. Adams C.D. Antman E.M. Anderson J.L. Hunt S.A. Halperin J.L. Nishimura R. Ornato J.P. Page R.L. Riegel B. Blanc J.J. Budaj A. Dean V. Deckers J.W. Despres C. Dickstein K. Lekakis J. McGregor K. Metra M. Morais J. Osterspey A. Tamargo J.L. Zamorano J.L. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for practice guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.Circulation. 2006; 114: e385-e484Crossref PubMed Scopus (994) Google Scholar The patient population has been described in a previous study.15Rijnierse M.T. van der Lingen A.L. Weiland M.T. de Haan S. Nijveldt R. Beek A.M. van Rossum A.C. Allaart C.P. Clinical impact of cardiac magnetic resonance imaging versus echocardiography-guided patient selection for primary prevention implantable cardioverter defibrillator therapy.Am J Cardiol. 2015; 116: 406-412Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar For the present study, patients were included when CMR was performed within 6 months before ICD implantation. CMR was typically performed for LVEF assessment, detection of LV thrombus, guiding of LV lead placement by scar assessment in resynchronization therapy, or as part of other study protocols. Exclusion criteria were chronic atrial fibrillation, atrial flutter, or when no follow-up data were available. Primary prevention was defined as no history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF; >48 hours after acute myocardial infarction). Patient characteristics before device implantation were collected from medical records. The Medical Ethics Review Committee of the VU University Medical Center approved the data collection and management of this study. CMR studies were performed on a 1.5-T whole body scanner (Magnetom Sonata/Avanto; Siemens, Erlangen, Germany) using a dedicated phased array body coil as described previously.15Rijnierse M.T. van der Lingen A.L. Weiland M.T. de Haan S. Nijveldt R. Beek A.M. van Rossum A.C. Allaart C.P. Clinical impact of cardiac magnetic resonance imaging versus echocardiography-guided patient selection for primary prevention implantable cardioverter defibrillator therapy.Am J Cardiol. 2015; 116: 406-412Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Cine imaging was performed using a retrospectively electrocardiogram-gated, steady-state free precession sequence during breath holds in mild expiration. Standard long-axis slices were acquired from the 4-, 3-, and 2-chamber views. Subsequently, consecutive short-axis slices were acquired, fully covering the LV. Late gadolinium enhanced (LGE) images were acquired approximately 10 to 15 minutes after the administration of 0.2 mmol kg−1 gadolinium diethylenetriamine penta-acetate in the similar orientations as used in the cine images, using a 2-dimensional (2D) segmented inversion-recovery gradient echo sequence. Images were analyzed using the dedicated software package MASS (Mass v.5.1 2010-EXP beta; Medis, Leiden, the Netherlands). Endocardial LA contours and length were drawn manually in both the apical 2- and 4-chamber views in the frames just before mitral valve opening to obtain maximum LA volume (LAVmax) and immediately after mitral valve closure for minimum LA volume (LAVmin; Figure 1). LA length (L) was defined as the distance from the center of the mitral annulus to the posterior border of the LA area, perpendicular to the mitral annular plane. The LA appendage and pulmonary veins were excluded from the LA measurements. LA volumes were calculated using the biplane area-length formula: LAV=8(A1)(A2)3π(L), according to the guidelines of the American Society of Echocardiography and European Association of Cardiovascular Imaging, where A1 and A2 represent the planimetered LA areas in the 2- and 4-chamber views, whereas for L, the shortest length of both views was used.16Lang R.M. Badano L.P. Mor-Avi V. Afilalo J. Armstrong A. Ernande L. Flachskampf F.A. Foster E. Goldstein S.A. Kuznetsova T. Lancellotti P. Muraru D. Picard M.H. Rietzschel E.R. Rudski L. Spencer K.T. Tsang W. Voigt J.U. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular imaging.Eur Heart J Cardiovasc Imaging. 2015; 16: 233-270Crossref PubMed Scopus (4331) Google Scholar LAEF was calculated as LAVmax−LAVminLAVmax×100. LV end-systolic and end-diastolic volumes (LVEDV and LVESV) were measured using a standard method, and LVEF was calculated. Finally, LGE short-axis images were outlined manually at the endocardial and epicardial borders. Myocardial scar size was quantified automatically using the full width at half-maximum method.17Flett A.S. Hasleton J. Cook C. Hausenloy D. Quarta G. Ariti C. Muthurangu V. Moon J.C. Evaluation of techniques for the quantification of myocardial scar of differing etiology using cardiac magnetic resonance.JACC Cardiovasc Imaging. 2011; 4: 150-156Crossref PubMed Scopus (429) Google Scholar Scar size was expressed as total grams and percentages of LV mass. All CMR images were analyzed by experienced observers who were blinded to clinical follow-up data. Clinical follow-up with device interrogation was routinely performed with regular intervals of 6 months. The ICDs were typically programmed according to the PREPARE study with detection rates of > ∼180 beats/min (VT zone) and > ∼250 beats/min (VF zone), extended detection intervals of 30/40 ventricular beats or 8/10 ventricular beats plus a 5 to 8 seconds delay, depending on the device manufacturer, and appropriate utilization of antitachycardia pacing (ATP).18Cantillon D.J. Wilkoff B.L. Antitachycardia pacing for reduction of implantable cardioverter-defibrillator shocks.Heart Rhythm. 2015; 12: 1370-1375Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 19Wilkoff B.L. Williamson B.D. Stern R.S. Moore S.L. Lu F. Lee S.W. Birgersdotter-Green U.M. Wathen M.S. Van Gelder I.C. Heubner B.M. Brown M.L. Holloman K.K. Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study.J Am Coll Cardiol. 2008; 52: 541-550Crossref PubMed Scopus (464) Google Scholar Event transmissions of patients connected with home monitoring were reviewed instantly when they occurred. All recorded events and ADT were reviewed by specialized cardiac technicians or by electrophysiologists. ADT was defined as an episode of ATP and/or defibrillation shock to terminate VT or VF. The primary end point was defined as the occurrence of first ADT. The secondary end point was defined as either the occurrence of ADT or all-cause mortality. Continuous data were expressed as means ± SD and were compared using the Student t test or Mann-Whitney U test when appropriate. Dichotomous and categorical data were expressed as frequencies and percentages and were compared using the chi-square test or, when appropriate, the Fisher's exact test. Univariable and multivariable Cox proportional hazard regression analyses were performed to identify predictors of the primary and secondary end points. Multivariable Cox proportional hazards models were performed using backward elimination with inclusion of variables with a p value below 0.10 in univariable Cox analysis. Scar size was evaluated in a separate multivariable model (model 2) for the subgroup with LGE available (n = 166). Both LAVmax index and LVESV index were not entered in multivariable analyses due to significant collinearity with LAVmin index and LVEDV index, respectively (correlation coefficients >0.90). Patients were categorized into low- and high-risk groups according to the median of LAEF (38.7%). In addition, patients with ICMP were categorized into low- and high-risk groups using the median of scar size (15.5 g), whereas DCMP patients were separately divided according to the presence or absence of scar size (median 0 g). Finally, a combined risk factor score was generated consisting of LAEF and scar size: 0 risk factors (both LAEF > median and scar size < median), 1 risk factor (LAEF < median or scar size > median), and 2 risk factors (both LAEF < median and scar size > median). Time to the primary and secondary end points were compared between risk groups using Kaplan-Meier curves and the log-rank test. A p value of 0.05 or less was considered statistically significant. All statistical analyses were performed using SPSS software package, version 20.0 (IBM SPSS Statistics, Chicago, Illinois). In total, 240 patients were evaluated. Eleven patients showed insufficient CMR image quality due to severe motion artifacts or irregularity in heart rhythm and were excluded from the analysis. Therefore, 229 patients were included in the present study. Clinical baseline characteristics are presented in Table 1. Total median follow-up time was 3.9 years (interquartile range 2.5 to 5.7 years). The primary end point ADT was reached in 62 patients (27%). The VA was terminated by ATP in 40 of 62 patients (65%) and by a primary defibrillation shock in 13 of 62 patients (21%). In addition, in 9 of 62 patients (15%), ATP was unsuccessful and followed by a successful shock. The defibrillation shocks were delivered in the VF zone in 12 of 22 patients and VT zone in 10 of 22 patients. Patients who experienced ADT were more likely to be men and showed a trend toward a higher creatinine level (p = 0.06) compared with patients without ADT.Table 1Baseline characteristicsVariableN(%), median (interquartile range), or mean ± standard deviationStudy population(n=229)Appropriate device therapyP-value(ADT vs. no ADT)Yes(n=62)No(n=167)Men156 (68%)51 (82%)105 (63%)0.005Age (years)63 ± 1061 ± 1064 ± 100.13Body mass index (kg/m2)26 ± 427 ± 426 ± 40.48Ischemic cardiomyopathy140 (61%)41 (66%)99 (59%)0.35Percutaneous coronary intervention/coronary arterial bypass grafting112 (49%)34 (55%)78 (47%)0.27Resynchronization therapy107 (47%)29 (47%)78 (47%)0.99Paroxysmal atrial fibrillation19 (8%)2 (3%)17 (10%)0.09Non-sustained ventricular tachycardia27 (12%)8 (13%)19 (11%)0.75New York heart association functional class:∗Data available for n = 178.0.79†Compared using the chi-square test for trend. I31 (17%)12 (24%)19 (15%) II73 (41%)12 (24%)61 (47%) III74 (42%)25 (51%)49 (38%)Medication: Beta blockers179 (78%)46 (74%)133 (80%)0.38 Angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers197 (86%)50 (81%)147 (88%)0.15 Diuretics160 (70%)42 (68%)118 (71%)0.67 Digoxin6 (3%)2 (3%)4(2%)0.66 Amiodarone10 (4%)3 (5%)7 (4%)1.00 Sotalol4 (2%)1 (2%)3 (2%)1.00 Statins148 (65%)42 (68%)106 (64%)0.55Creatinine (μmol/L)89 (75-111)98 (79-118)88 (73-107)0.06§Compared using the Mann-Whitney U test.QRS duration (ms)‡Data available for n = 218.128 ± 32124 ± 29130 ± 330.24Diuretics include mineralocorticoid receptor antagonists.ADT = appropriate device therapy.∗ Data available for n = 178.† Compared using the chi-square test for trend.‡ Data available for n = 218.§ Compared using the Mann-Whitney U test. Open table in a new tab Diuretics include mineralocorticoid receptor antagonists. ADT = appropriate device therapy. CMR characteristics compared between patients with ADT and without ADT are presented in Table 2. Median time between CMR and ICD implantation was 56 days (interquartile range 8 to 92). No differences were observed in (indexed) LAVmin or LAVmax. However, patients who received ADT showed significant lower LAEF (p = 0.003). In addition, a trend was observed toward a larger LVEDV in patients who received ADT (p = 0.06), although LVEF did not differ. LGE data were available in 166 patients. Main reasons for missing LGE data were impaired renal function, LGE assessment not requested, or LGE assessment during a previous CMR assessment > 6 months before ICD implantation. Total scar size, quantified in grams, was significantly larger in patients who experienced ADT (n = 41). Supplementary Table 1 lists a comparison of CMR characteristics between patients with ICMP and DCMP. Mean LAEF did not differ between both CMP groups. Patients with DCMP showed significant larger (indexed) LV volumes and lower LVEF compared with patients with ICMP (all p <0.001). LGE assessment was available in 104 of 140 patients (74%) with ICMP and 62 of 89 patients with DCMP (70%; p = 0.45). LGE was more often observed and of greater extent in patients with ICMP.Table 2Cardiovascular magnetic resonance imaging characteristics according to appropriate device therapyVariableN(%), median (interquartile range), or mean ± standard deviationStudy population(n=229)Appropriate device therapyP-value(ADT vs. no ADT)Yes(n=62)No(n=167)Maximum left atrial volume (mL)104 (84-132)105 (82-135)103 (85-130)0.91†Compared using the Mann-Whitney U test.Maximum left atrial volume index (mL/m2)54 (45-66)54 (42-66)56 (46-66)0.61†Compared using the Mann-Whitney U test.Minimum left atrial volume (mL)63 (48-88)66 (51-99)62 (47-85)0.19†Compared using the Mann-Whitney U test.Minimum left atrial volume index (mL/ m2)33 (25-45)34 (25-50)32 (25-44)0.38†Compared using the Mann-Whitney U test.Left atrial emptying fraction (%)36 ± 1432 ± 1438 ± 140.003Left ventricular end-diastolic volume (mL)304 (253-378)331 (270-285)298 (249-376)0.06†Compared using the Mann-Whitney U test.Left ventricular end-diastolic volume index (mL/m2)162 (137-195)170 (139-199)159 (135-191)0.20†Compared using the Mann-Whitney U test.Left ventricular end-systolic volume (mL)234 (180-308)253 (195-315)228 (177-306)0.11†Compared using the Mann-Whitney U test.Left ventricular end-systolic volume index (mL/m2)124 (97-155)131 (101-155)123 (94-152)0.27†Compared using the Mann-Whitney U test.Left ventricular ejection fraction (%)24 ± 724 ± 623 ± 80.79Left ventricular mass (g)125 ± 38128 ± 32124 ± 400.51Left ventricular mass index (g/m2)65 ± 1865 ± 1665 ± 180.82Late gadolinium enhancement present (n)∗Data available for n = 166.122 (74%)33 (81%)89 (71%)0.24Scar size (g)∗Data available for n = 166.9 (0-17)14 (4-21)6 (0-16)0.03†Compared using the Mann-Whitney U test.Scar size (%)∗Data available for n = 166.7 (0-16)13 (3-20)6 (0-16)0.051†Compared using the Mann-Whitney U test.ADT = appropriate device therapy.∗ Data available for n = 166.† Compared using the Mann-Whitney U test. Open table in a new tab ADT = appropriate device therapy. The cumulative 5-year incidence of ADT was 27% for the total study population and did not differ between patients with ICMP or DCMP (log-rank p = 0.55). Parameters that were significantly associated with the occurrence of ADT in univariable Cox analyses included male gender, creatinine level, LAVmin index, LAEF, and scar size (Table 3). The multivariable Cox model for the total study population (model 1, excluding scar size) revealed that male gender and LAEF were independent predictors of ADT. When adding scar size to the multivariable analysis (model 2), LAEF and scar size remained independent predictors of ADT (Table 3). The secondary end point of ADT or mortality occurred in 97 of 229 patients (42%), with a cumulative incidence of 40% at 5 years. Univariable Cox regression analyses revealed that male gender, nonsustained VT, creatinine level, LAVmin index, LAEF, LVEDV index, LVESV index, and LVEF were significantly related to the occurrence of ADT or mortality (Table 4). In multivariable analysis (model 1), LAEF, nonsustained VT, creatinine level, and LVEDV index independently predicted ADT or mortality. When adding scar size to the multivariable model (model 2), LAEF and LVEDV index remained the only independent predictors of ADT or mortality, whereas for scar size, only a trend was observed.Table 3Univariable and multivariable Cox regression analyses for predicting appropriate device therapyParameterUnivariable analysisMultivariable model 1: Total study populationMultivariable model 2: Subgroup with LGE availableHR (95% CI)P-valueHR (95% CI)P-valueHR (95% CI)P-valueMale gender2.55 (1.33-4.90)0.0052.13 (1.10-4.13)0.03--Age (per year)0.99 (0.96-1.01)0.36Ischemic cardiomyopathy1.17 (0.69-1.99)0.55Resynchronization therapy1.01 (0.61-1.66)0.98Paroxysmal atrial fibrillation0.31 (0.08-1.29)0.11Non-sustained ventricular tachycardia1.36 (0.65-2.86)0.42New York heart association functional class∗Data available for n = 178.0.97 (0.65-1.44)0.88Beta blockers0.75 (0.43-1.33)0.33Angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers0.65 (0.35-1.22)0.18Creatinine (per 10 μmol/L)1.07 (1.02-1.11)0.0021.04 (1.00-1.09)0.052--QRS duration (per 10 ms)0.96 (0.88-1.04)0.27Maximum left atrial volume index (per 10 mL/m2)1.03 (0.90-1.19)0.64Minimum left atrial volume index (per 10 mL/m2)1.15 (1.01-1.31)0.03----Left atrial emptying fraction (per 10%)0.73 (0.61-0.87)0.0010.77 (0.64-0.93)0.0060.75 (0.60-0.93)0.008Left ventricular end-diastolic volume index (per 10 mL/m2)1.03 (0.97-1.08)0.34Left ventricular end-systolic volume index (per 10 mL/m2)1.02 (0.97-1.08)0.50Left ventricular ejection fraction (per %)1.00 (0.96-1.03)0.76Late gadolinium enhancement present†Data available for n = 166.1.44 (0.66-3.12)0.36Scar size (per g)†Data available for n = 166.1.03 (1.01-1.06)0.011.03 (1.00-1.05)0.03Scar size (per %)†Data available for n = 166.1.02 (0.99-1.06)0.16Model 1: excluding scar size (total study population). Model 2: including scar size (subgroup with late gadolinium enhancement assessment available).CI = confidence interval; HR = hazard ratio.∗ Data available for n = 178.† Data available for n = 166. Open table in a new tab Table 4Univariable and multivariable Cox regression analyses for predicting appropriate device therapy or mortalityParameterUnivariable analysisMultivariable model 1: Total study populationMultivariable model 2: Subgroup with LGE availableHR (95% CI)P-valueHR (95% CI)P-valueHR (95% CI)P-valueMale gender2.00 (1.23-3.25)0.0051.54 (0.93-2.53)0.09--Age (per year)1.01 (0.99-1.03)0.34Ischemic cardiomyopathy1.01 (0.67-1.53)0.96Resynchronization therapy1.34 (0.90-2.00)0.15Paroxysmal atrial fibrillation0.50 (0.20-1.24)0.13Non-sustained ventricular tachycardia1.67 (0.96-2.89)0.071.78 (1.02-3.10)0.04--New York heart association functional class∗Data available for n = 178.1.05 (0.75-1.46)0.78Beta blockers0.90 (0.56-1.44)0.65Angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers0.68 (0.41-1.13)0.14Creatinine (per 10 μmol/L)1.08 (1.04-1.11)<0.0011.08 (1.04-1.11)<0.001--QRS duration (per 10 ms)0.99 (0.93-1.06)0
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