Citations

Background Little is known about the effects of permanent transvenous device leads on bioprosthetic tricuspid valve (BTV) function. Hypothesis The goal of this study was to test the hypothesis that transvalvular device leads promote clinically significant BTV regurgitation. Methods A retrospective review of 58 patients who underwent BTV implantation and subsequently required endocardial pacemaker (n=52) or defibrillator (n=6) lead implantation through the BTV was conducted. Patient and prosthesis characteristics, lead type, and clinical events were collected. The incidence and severity of prosthetic tricuspid regurgitation (TR), determined by Doppler echocardiography, was compared to 265 patients who underwent BTV implantation without undergoing subsequent transvalvular device lead implantation. Results Over a mean follow up of 25 months, 5 patients (9%) with a transvalvular lead developed ≥ moderate prosthetic TR compared to 12 patients (5%) in the control group (P = 0.20). Kaplan Meier survival analysis revealed no significant difference in the incidence of TR in BTV patients with and without transvalvular leads (p = 0.45). Clinically significant prosthetic TR in patients with and without a transvalvular lead more commonly occurred 2 years or later after lead implantation or BTV implantation (4/5, 80% and 10/12, 83%). Conclusions Compared to BTV controls, there was no significant difference in the incidence of ≥ moderate prosthetic TR in patients with a transvalvular pacemaker or defibrillator lead (p = 0.45). Transvalvular lead implantation appears to be an acceptable approach for patients with a BTV who require permanent pacemaker or defibrillator placement.

Background: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people. Recently, a patient with HCM with paroxysmal atrial fibrillation (AF) and sinoatrial block was found to have a missense mutation, E169K, in the junctophilin 2 (JPH2) protein. Loss of JPH2 has been shown to affect intracellular Ca2+ release in the heart. To date, no study has evaluated the effect of E169K mutation on Ca2+ handling and arrhythmogenesis. Hypothesis: The JPH2 E169K mutation promotes sarcoplasmic reticulum Ca2+ leak causing abnormal atrial conduction and AF. Methods and Results: We evaluated our hypothesis by generating 3 mice that overexpressed 1) JPH2 with E169K mutation (EK-Tg), 2) WT JPH2 (WT-Tg) and 3) JPH2 with inactive P584S mutation (PS-Tg). On Western Blot, JPH2 expression was increased by 2-3 fold in all the mouse groups compared to non-transgenic controls. Echocardiography at 6 months of age revealed normal fractional shortening in all mice. At baseline, EK-Tg mice had a shorter RR interval (104±1 ms, n=10) vs. WT-Tg (123±5 ms, n=8, p=0.001) and PS-Tg mice (121±5 ms, n=5, p<0.001). EK-Tg mice also had a shorter PR interval (36±1 ms, n=10) vs. WT-Tg (41±1 ms, n=8, p=0.01) and PS-Tg mice (39±1 ms, n=5, p=0.15). On intracardiac electrophysiology studies, EK-Tg mice had shorter AVERP (39±2 ms, n=10) vs. WT-Tg (51±2 ms, n=8, p=0.005) and PS-Tg mice (48±3 ms, n=5, p=0.05). On overdrive pacing of the atria in the presence of epinephrine and caffeine, EK-Tg mice had a 57% incidence of AF (n=10) vs. 21% in WT-Tg (n=8, p<0.05) and 33% in PS-Tg mice (n=5, p=0.2). Isolated cardiomyocytes from EK-Tg mice had a higher Ca2+ spark frequency (6.7±0.8 events/100 um/s, n=20) vs. cardiomyocytes from WT-Tg (1.8±0.5 events/100 um/s, n=10, p<0.001) and PS-Tg mice (3.3±1.0 events/100 um/s, n=16, p<0.05). Lastly, JPH2 levels were lower in RyR2 channels immunoprecipitated from EK-Tg mice vs. RyR2 from WT-Tg mice (65% vs. 100%, p<0.05). Conclusion: The JPH2 mutation, E169K, leads to reduced binding of JPH2 with RyR2, increased SR Ca2+ leak, abnormal atrial conduction and AF. The data suggest that JPH2 may serve as a critical stabilizing molecule for RyR2; further approaches to stabilize this interaction may lead to improved control of AF in susceptible populations.

Background: Depression is prevalent in adults with cardiovascular disease; however, the association between depression and death in older adults treated with percutaneous coronary intervention (PCI) is not known. Method: We prospectively studied 596 patients 65 years of age or older undergoing PCI at Mayo Clinic (Rochester, MN and Franciscan Skemp Hospital in La Crosse, WI) from October 2005 through September 2008. Depression was assessed using the validated and reliable Center for Epidemiological Studies Depression (CES-D) scale. Patients were categorized into groups by depression symptom severity: none/mild (CES-D <16; referent), moderate (CES-D 16-21), or moderate/severe (CES-D>21). Patients were followed annually for death. Results: Mean age of patients was 75.0±6.4 years; 31% were women, 98.0% were white. There were 461 patients (77.3%) that were not depressed and 135 patients (22.7%) that were depressed; 67 patients (11.3%) had moderate depressive scores (CES-D 16-21) and 68 patients (11.4%) had moderate/severe scores (CES-D >21). Groups were similar with respect to baseline characteristics. After a median follow-up of 36 months, there were 74 deaths, and patients with moderate/severe depressive symptom scores had a higher cumulative incidence of mortality (p = 0.036 by log-rank) (Figure). In multivariable analysis, CES-D score >21 was independently predictive of all-cause mortality (HR 1.90; 95% CI 1.02-3.53; p = 0.043), along with other covariates, including age (HR 1.88; 95% CI 1.31-2.68), comorbidity (Charlson Index) (HR 1.08; 95% CI 1.02-1.15), and diabetes mellitus (HR 2.04; 95% CI 1.26-3.30). Conclusion: Over one-fifth of older adults undergoing PCI met criteria for depression and those with high depressive scores reflecting greater self-perceived depressive symptoms had worse survival. Recognition of depressive symptoms in older adults treated with PCI identifies a cohort at higher risk of adverse outcomes.

Device infection is associated with increased mortality in cardiovascular implantable electronic device (CIED) recipients. However, published data regarding clinical predictors of mortality in patients with CIED infection are limited. In current investigation, we sought to identify patient and device-related factors associated with mortality in CIED infection cases. We performed a retrospective review of all cases of CIED infection admitted to Mayo Clinic Rochester from 1991 to 2008. Survival data were obtained from hospital medical records and United Sates Social Security Index. Key data regarding patient demographics, device features, comorbid conditions, clinical presentation, echocardiographic findings and management strategies were abstracted. Potential risk factors for short (30-day) and long-term mortality were analyzed using univariate and multivariable logistic and Cox proportional hazards regression models, respectively. 415 cases of CIED infection were identified from the institutional database. The mean duration of follow-up for the 243 patients who were alive at last follow-up was 6.9 years. In multivariable model, congestive heart failure (CHF, Odds ratio 9.31, 95% CI 2.08-41.67), chronic corticosteroid use (OR 4.04, 1.40-11.60) and presentation with CIED-related infective endocarditis (CIED-IE), (OR 5.6, 2.25-13.92) were associated with increased odds of short-term mortality. Independent predictors of long-term mortality on multivariable model included patients' age (hazard ratio for 10-year increase 1.2, 95% CI 1.06-1.36), CHF (HR 2.01, 1.42-2.86), metastatic malignancy (HR 5.99, 1.67-21.53), corticosteroid use (HR 1.97, 1.22-3.18), renal failure (HR 1.94, 1.37-2.74) and CIED-IE (HR 1.68, 1.17-2.41). Our investigation provides some novel insights into predictors of short- and long-term mortality in CIED infection cases. While comorbid conditions and immunocompromised host status were primary determinants of both short- and long-term mortality, complicated device infection (CIED-IE) is the only predictor that presents an opportunity for intervention where mortality may be reduced by early diagnosis and expedited device removal.

Background: The 2010 AHA Guidelines state rescuers should perform chest compressions (CCs) of at least 2 inches in depth for adult cardiac arrest patients. Although the pediatric guidelines recommend adjustment of CC depth based upon anteroposterior chest dimension, there is no such recommendation for adults. Purpose: To determine 1) whether prehospital providers intuitively vary CC depth in adults according to patient size and 2) whether implementation of real-time audiovisual CPR feedback (RTAVF) impacts weight/CC depth variation. Methods: CC quality data were prospectively collected prior to (9/08-4/10; Pre-feedback) and after (5/10-12/10; Post-feedback) implementation of an RTAVF system (ZOLL Medical, Chelmsford MA) from 3 EMS agencies. The RTAVF includes a visual display of absolute CC depth and gives audio prompts when depth is outside of the Guideline-recommended range. Among 363 cases of adult, non-traumatic out-of-hospital cardiac arrest (OHCA), body weight was estimated by EMS in 249 patients (study group; 66%). CPR quality data were available for all cases via code review software. Results: 168 Pre-feedback and 81 Post-feedback study group cases (mean 64±16 years, 68% male). Mean estimated body weight was 201 lbs (quartiles 161, 231; range 70-451) and was not different between groups. CC depth increased significantly with RTAVF use (Pre-feedback = 1.77, 95% confidence interval [CI]:1.71-1.83 in.; Post-feedback = 2.10, CI: 2.04-2.15 in.; p<0.001). CC depth did not vary significantly by patient gender or age (p>0.4). Multivariate linear regression (r 2 =0.23, p<0.001 for model) revealed a significant increase in CC depth with estimated weight in both periods (0.07in/50lbs, p<0.001) after controlling for the presence of RTAVF. RTAVF was not an effect-modifier of the relationship between estimated weight and CC depth (p-value for interaction term=0.4). Conclusion: Although not specifically recommended in the 2010 AHA Guidelines for adults, rescuers may instinctively and/or intentionally adjust CC depth according to patient size. In this setting, weight/CC depth adjustments occurred both without and with real-time feedback. Follow-up studies are needed to determine the potential effect of size-adjusted CC depth on patient outcome.

BACKGROUND: For sudden collapse from out-of-hospital cardiac arrest (OHCA) in adults, bystander chest compression-only CPR (COCPR) results in equivalent or better survival compared with conventional CPR with rescue breathing. However, patients who arrest from a non-cardiac cause may also receive COCPR even though rescue breathing might benefit them. We sought to determine whether lay rescuers appropriately provided COCPR or conventional CPR depending on the suspected etiology of OHCA. METHODS: Analysis of a statewide, Utstein-style registry of adult OHCA during a large-scale campaign endorsing COCPR for adults who suddenly collapse. The relationship between bystander CPR (both COCPR and conventional CPR), presumed arrest etiology, and survival to hospital discharge were evaluated. Means and 95% confidence intervals (CI) were calculated. FINDINGS: A total of 7,652 adult OHCAs not witnessed by EMS were analyzed from 10/04 to 09/10. After exclusion of non-lay bystanders and arrests in medical facilities, presumed cardiac etiology and non-cardiac etiology OHCA totaled 4,913 and 1,202, respectively. The presumed specific non-cardiac etiologies were non-cardiopulmonary (e.g. overdose, suicide, subarachnoid hemorrhage) (57%), trauma (27%), and respiratory (16%). All-rhythm survival was 7.0% (CI: 6.3 - 7.8) for cardiac etiologies and 3.3% (CI: 2.3 - 4.3) for non-cardiac (p<0.001). Bystander CPR was provided for 33% (CI: 31.4 - 34.1) of victims with presumed cardiac causes versus 28% (CI: 25.6 - 30.7) for non-cardiac causes (p=0.002). Presumed respiratory causes of OHCA had a much lower proportion of COCPR (8.3%, CI: 4.4 - 12.2) than cardiac causes (18.0%, CI: 16.9 - 19.1, p<0.001). Survival for non-cardiac cases was: 4.4% (CI 0.9 - 7.8) for conventional CPR, 3.5% (CI: 0.9 - 6.0) for COCPR, and 3.1% (CI: 2.0 - 4.3) for no CPR (p = 0.66). CONCLUSIONS: In the setting of a large-scale, statewide public health campaign endorsing lay rescuer COCPR for adults who suddenly collapse and are not breathing normally, bystanders were much less likely to perform COCPR on OHCA victims who might benefit from rescue breathing. Furthermore, when COCPR was performed on presumed non-cardiac cause arrest victims, there was no demonstrable negative impact on survival.

Early after correction of mitral valve (MV) regurgitation, systolic function of the left ventricle (LV) declines, but the underlying mechanisms of this phenomenon are unknown. Most studies in this area have analyzed LV function at one week postoperatively or later. In a retrospective study from our Clinic, Enriquez-Sarano et al. reported a decline in LV ejection fraction (EF) from 62% to 52% ( P <0.001) in 217 patients with organic mitral regurgitation who were studied within the first year after MV replacement or repair. This decline was due to decreased left ventricular end-diastolic dimension (LVEDD) and minimal change in left ventricular end-systolic dimension (LVESD). Surgical investigators have compared the outcomes for different techniques of MV replacement and studies indicate that decline in EF may be mitigated by chordal preservation. It has been suggested that early postoperative measurements of cardiac geometry and function are confounded by the effects of global ischemia, reperfusion, and myocardial protection. Indeed, some clinicians have suggested that reduced EF early after MV repair results from myocardial dysfunction that, in turn, is related to poor myocardial protection. In addition, cardiac loading conditions change dramatically early after operation. We speculated that a postoperative decline in LV systolic indexes (eg, EF, FAC, and FS) may be interpreted as a volumetric adjustment of the heart to the correction of mitral regurgitation rather than as postoperative LV dysfunction due to impaired myocardial contractility, and clinical studies support this hypothesis. Soon after MV repair, the LV remodels gradually. Very early after correction of mitral regurgitation, the LVESD increases, preventing an acute increase in forward stroke volume. Within the next few postoperative days, the LVEDD begins to decrease and the LVESD changes accordingly to maintain a normal forward stroke volume; the remodeling occurs when neurohumoral mechanisms of the body adapt to the new hemodynamic milieu. This progression of remodeling may explain why some investigators have observed unchanged LV systolic and decreased diastolic size on the first postoperative echocardiogram about a week after MV repair.

Cristiane Maki-Nunes, 2011 Finalist and Presenting Author

Thais Coutinho, 2011 Finalist and Presenting Author

Peter J. Psaltis, 2011 Finalist and Presenting Author