Herges, Regina M.

BackgroundPatients with preexisting mild cognitive impairment or dementia may be at increased risk for developing cardiac device complications due to an impaired ability to follow postimplant care instructions. We sought to determine whether rates of infection, lead dislodgement, or appropriate or inappropriate implantable cardioverter defibrillator (ICD) shocks are increased in this population.MethodsMedical charts of 561 patients with mild cognitive impairment or dementia who underwent pacemaker (PM) or ICD implantation between January 2002 and October 2009 at Mayo Clinic were identified. A total of 134 patients who were diagnosed with cognitive impairment or dementia before device implantation or within 1 year of implantation were compared with 134 matched controls. Information was collected on patient characteristics, comorbid medical conditions, ejection fraction, complications, device type, device therapy, and mortality. Device information was prospectively entered into a database and retrospectively reviewed.ResultsOf the 134 patients with mild cognitive impairment and dementia, 99 underwent PM implantation and 35 underwent ICD implantation. Compared to controls, there was no difference in patient characteristics, ejection fraction, or comorbidities except for diabetes, which was more prevalent in the cognitively impaired and demented group (18.7% vs 30.6%, P = 0.02). There was no difference in device therapy and complications (14.4% vs 5.8%, P = 0.268). However, there was a decreased survival in patients with cognitive impairment and dementia when compared to the control group (42% vs 67% at 5 years, P = 0.007).ConclusionPatients with cognitive impairment and standard device indications are not at increased risk for device complications and therapy but their survival is much lower than in matched controls. The cause of this lower survival is unknown but may be related to the underlying neurological disease. Presence of cognitive impairment should therefore be considered when contemplating implantation of a cardiac device.

Objective— Left atrial blood stasis is associated with increased risk for left atrial appendage thrombus (LAAT) and stroke in atrial fibrillation (AF). Von Willebrand factor (VWF) is associated with thromboembolism in AF. VWF thrombogenic activity is proportional to multimer size, which is regulated by VWF-cleaving protease (ADAMTS13). Methods and Results— To assess the association between left atrial blood stasis and VWF-ADAMTS13 system, plasma VWF antigen (VWF:Ag), VWF activity (VWF:Act), and ADAMTS13 activity were measured in 414 consecutive patients with nonvalvular AF (age 63±13 years; 25% women) and in 100 patients (age 64±14 years; 39% women) with normal sinus rhythm. Spontaneous echocardiographic contrast (SEC), left atrial appendage emptying velocity, and LAAT were assessed by transesophageal echocardiography. Presence and intensity of SEC varied directly with VWF:Ag and VWF:Act but not with ADAMTS13 activity. AF patients with LAAT had higher VWF:Ag (200±61 versus 155±52, P =0.0006) and VWF:Act (179±57 versus 141±51 P =0.0026) compared with those without LAAT. VWF:Ag and VWF:Act were independent predictors of LAAT after adjustment for CHADS 2 score ( P =0.0179 and P =0.0497, respectively). Conclusion— The association between VWF and SEC may explain the thrombotic propensity in AF. Elevated VWF:Ag may help identify AF patients at risk for LAAT.

Background— The efficacy of radiofrequency ablation for atrial fibrillation (AF) in patients with left ventricular (LV) systolic dysfunction and isolated diastolic dysfunction is uncertain. Methods and Results— A prospective cohort of patients with normal and abnormal LV function underwent ablation for antiarrhythmic drug (AAD)-refractory AF. Three groups were compared: 111 patients with systolic dysfunction, defined as LV ejection fraction (LVEF) ≤40%; 157 patients with isolated diastolic dysfunction but preserved LVEF ≥50%; and 100 patients with normal LV function. The primary end point was AAD-free AF elimination at 1 year after ablation. This end point was achieved in 62% of patients with systolic dysfunction, 75% of those with diastolic dysfunction, and 84% of controls ( P =0.007). AF control on or off AADs was achieved in 76% of patients with systolic dysfunction, 85% of those with diastolic dysfunction, and 89% of controls ( P =0.08). In the systolic dysfunction group, 49% experienced an increase in LVEF by ≥5% after ablation, of which 64% achieved normal LVEF. In the diastolic dysfunction group, 30% of patients demonstrated at least 1 grade improvement in diastolic dysfunction. Multivariable analysis demonstrated an increased relative risk of arrhythmia recurrence of 1.8 (95% CI, 1.1 to 3.1; P =0.02) in systolic dysfunction and 1.7 (1.0 to 2.7; P =0.04) in isolated diastolic dysfunction compared with normal function. Conclusions— Although an ablative approach for AF in patients with systolic or diastolic dysfunction is associated with an increased long-term recurrence risk, there is potential for substantial quality-of-life improvement and LV functional benefit.

Background— The objective of the present study was to investigate the effect of cardiac resynchronization therapy (CRT) on cardiac autonomic function. Methods and Results— This prospective study included 45 consecutive patients with heart failure who received CRT devices with defibrillator and 20 age-matched, healthy control subjects. At baseline and 3 months and 6 months after CRT, we assessed New York Heart Association (NYHA) class, 6-minute walk distance, plasma sympathetic biomarker nerve growth factor, echocardiography, heart rate variability and cardiac presynaptic sympathetic function determined by iodine 123 metaiodobenzylguanidine scintigraphy. After CRT, NYHA class improved by 1 class ( P <0.001), and left ventricular ejection fraction increased by 8% ( P <0.001). Along with improvement in the standard deviation of all normal-to-normal R-R intervals (85.63±31.66 ms versus 114.79±38.99 ms; P =0.004) and the standard deviation of the averaged normal-to-normal R-R intervals (82.62±23.03 ms versus 100.50±34.87 ms; P =0.004), the delayed heart/mediastinum (H/M) ratio increased (1.82 [0.58] versus 1.97 [0.59]; P =0.03), whereas the mean (SD) H/M washout rate was reduced (48% [19%] versus 37% [22%]; P =0.01). Twenty-two of 45 study patients responded to CRT, with a reduction of left ventricular end-systolic volume index >15%. Compared with nonresponders, responders had a higher delayed H/M ratio (2.11 versus 1.48; P =0.003) and lower H/M washout rate (37% versus 62%; P =0.003) at baseline. Conclusions— CRT improved sympathetic function. Cardiac sympathetic reserve may be a marker for the reversibility of failing myocardial function.

Background— Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. Methods and Results— Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy ( P =0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR ( P <0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. Conclusions— These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.