Citations

Background: During CPR in animals, chest compressions (CC) may produce passive volumes large enough to provide adequate ventilation. In humans, this mechanism may explain why continuous CCs have been associated with improved survival. We quantified the volume of passive ventilation during emergency department (ED) CCs to determine if compression-only CPR (COCPR) provides clinically significant gas exchange during resuscitation. Methods: In an urban ED, continuous flow and volume of air exhaled through an endotracheal tube were measured during the CC phase of manual CPR (between ventilations) with NICO monitors (Philip/Respironics) and recorded using LabView (National Instruments). Gas exchange with CC was quantified using Matlab (Mathworks) as the area under the flow curve (figure). CC quality was measured using accelerometer-based technology (R Series, ZOLL Medical). Results: Eight patients (6 male) aged 37-83 yrs [median age 51 yr (IQR 43-56)] who suffered out-of-hospital cardiac arrest (CA) and were transported and treated with CC in the ED were included. A total of 548 CCs [median depth 1.89 in (IQR=1.66, 2.29), median rate 128 CC/min (IQR=122-134) were analyzed over 30 min of CPR. Median tidal volume per CC was 17.3 mL (IQR=5.9-22.4). This was considerably less than measured dead space in all patients (median 118mL, IQR=93-143), regardless of CC depth. The figure illustrates a typical tracing in which ventilation volume dwarfs any passive ventilation occurring with CC. Conclusion: Late in CA, passive ventilation occurring during CCs appears to produce considerably less gas exchange than calculated dead space. The effectiveness of passive ventilation during early stages of CPR, when chest and lung compliance are greater, remains unknown. However, these findings suggest that the benefits of COCPR strategies may be related to reliably higher CC fraction and/or prevention of the negative effects of hyperventilation rather than from any passive ventilation.

Background: Left ventricle assist device (LVAD) support, a well established therapy in advanced CHF, improves renal function assessed by creatinine. While renal function in large numbers of continuous flow (CF) LVADs vs pulsatile flow (PF) LVADs has been evaluated at 3 mo., long term studies are needed with large numbers of CF vs PF devices. To date longer term analysis comparing renal function in CF vs PF devices have relied on a small number of CF devices. We evaluated renal function assessed by creatinine in a large number of CF (HM II) (n=119) devices and compared this to renal function in a group of subjects treated with PF devices (HM XVE) (n=8) at 6 mo. post implant. Our aim was to evaluate change in creatinine between 3 and 6 months in these groups. Methods and Results: Plasma creatinine was evaluated at 3 and 6 months in two groups: subjects with CF HM II (n=119) and PF LVAD (HM XVE, n=8). The data were collected from two centers in patients undergoing implant for destination or bridge to transplant therapy. Baseline creatinine was higher in the HM XVE group at baseline (BL), and decreased at 3 mo. (1.7 [1.1-2.1] vs 1.1 [0.8-1.5] mg/dL, p<0.05). BL creatine in the HM II group decreased at 3 mo as well (1.2 [1-1.5] vs 1.1 [0.9-1.3] mg/dL, p,0.05). Between 3 and 6 months there was no difference in degree of creatinine change in CF vs PF, however both groups had an increase in Creatinine in this time frame: PF (1.1 [0.8-1.5] vs 1.35 [1.05-1.9] mg/dL, p<0.05); CF (1.1 [0.9-1.3] vs 1.2 [0.92-1.4] mg/dL, p<0.05). Conclusion: This is the first study to demonstrate with large numbers of CF LVAD that creatinine does not incrementally increase between 3 and 6 mo. in comparison to PF LVAD. Further studies are required with large numbers of continuos flow LVADs evaluating the comparative effect of long term continuous flow vs pulsatile flow. Additionally, it remains important to identify surrogates of pulsatility in subjects with continuous flow devices and evaluate prognostic impact on renal function long term.

Introduction Current evidence suggests that abnormal ventriculo-vascular coupling may contribute to the development of atrial fibrillation (AF) by increasing ventricular filling pressures and consequently, left atrial pressure. Recent investigations have also suggested that inflammation might have a role in the pathophysiology of AF. We hypothesize that autoimmune vasculitis plays a significant role in the pathogenetic mechanism of AF. Methods In this longitudinal cohort study, residents of Olmsted County, MN with first- time diagnosed AF during 1980-2000 and a reference age- and sex-matched control group from the same underlying population and time period were identified and followed until death, or 2000. The relationship between autoimmune vasculitis and first documented AF was analyzed. Results Of a total of 8766 patients (mean age 61.1+14.9 years; 56% women), 691 (7.9%) were diagnosed with autoimmune vasculitis during the 20 year period. The prevalence of autoimmune vasculitis in the AF group was 9.9% and 5.9% in the control group; p <0.001, respectively. After adjusting for CAD and LV dysfunction, the odds of autoimmune vasculitis in AF was 1.7 times higher than in controls (OR 1.69, 95%; CI 1.42 - 2.01, p < 0.0001). AF patients with autoimmune vasculitis had a worse survival compared to controls; p=.0114 (log-rank test). Conclusion Autoimmune vasculitis strongly increases the risk of atrial fibrillation and portends shorter survival in the AF population. These observations may represent one mechanism linking increased arterial stiffness and inflammation in the pathogenesis and prognosis of AF as an age-related disorder.

Background: Disease progression in heart failure (HF) reflects multiple neurohormonal derangements resulting in adverse prognosis in the absence of overt clinical events. ST2 is up-regulated in response to cardiac injury/hemodynamic stress while modulating cardiac remodeling via inflammatory and apoptotic pathways. Accordingly, we evaluated changes in ST2 over time in conjunction with troponin T (cTnT) and BNP in ambulatory patients with chronic HF. Methods: A cohort of 191 NYHA class III-IV HF patients was prospectively evaluated with serial specimens collected every 3 months over a 2-year period. Primary end points were death or cardiac transplantation; secondary end points were combined death/transplantation and HF-related hospitalization. Plasma ST2 (Critical Diagnostics) was evaluated against contemporary cTnT (Roche 4th generation) and BNP (Shinogi) assays. Gender specific cut-points (>49.3 and >33.5 ng/mL for males and females, respectively) and a clinically defined optimal cut-point for ST2 (>35 ng/mL) were evaluated. Results: Time-dependent analyses (dichotomous and continuous variable) demonstrated ST2 gender specific cut-points were superior to a single ST2 cut-point and associated with an increased risk of death or transplantation (HR 4.8, 95% CI 2.8 to 8.3, p<0.0001) and combined death/transplantation/HF-hospitalization (HR 2.1, 95% CI 1.7 to 2.5, p<0.0001). Although cTnT remained the strongest predictor of death/transplantation (HR 3.2, 95% CI 1.6 to 5.4, p<0.0001) in multivariate analyses adjusted for cTnT and BNP, ST2 (HR 3.0, 95% CI 1.6 to 5.4, p=0.0003) added significantly to predictive accuracy. Furthermore, elevated ST2 was the only independent predictor of HF-hospitalization (HR 1.7, 95% CI 1.4 to 2.1, p<0.0001). In these models BNP was no longer significantly predictive (HR 1.2, 95% CI 0.7 to 2.2, p=0.58). Conclusions: Serial monitoring of changes in ST2 using gender specific cut-points adds to the diagnostic ability of cTnT in predicting mortality and/or transplantation in outpatients with chronic HF. ST2 uniquely predicts HF-hospitalization/death/transplantation, suggesting a serial monitoring strategy with cTnT and ST2 will optimize identification of HF patients at increased risk for events.

Introduction: Pulmonary hypertension (PH) is an independent marker of surgical morbidity. Right ventricular systolic pressure (RVSP) measured by transthoracic echocardiography (TTE), correlates poorly with pulmonary artery systolic pressure (PASP) measured by right heart catheterization, especially in PH. The correlation between TTE derived RVSP and intraoperative PASP, while under general anesthesia, is not known. In this study, the association between preoperative RVSP and intraoperative PASP was tested. Methods: All consenting adult surgical patients requiring intraoperative pulmonary pressure monitoring in a 2 year period were retrospectively identified. Patients who had TTE estimated RVSP ≥ 40 mmHg, measured within a week prior to the index surgery, were included. RVSP was calculated from tricuspid regurgitant velocity using the modified Bernoulli equation. For intraoperative PASP, the median of the first 10 minutes after PAC placement was used. CVP, arterial systolic pressure, minimum alveolar concentration of anesthetic (MAC) and basic demographic data were also collected. Agreement between RVSP and PASP was tested using the concordance correlation coefficient. Multivariate linear regression and Bland-Altman plot were used to further refine the analysis. Results: 129 patients met inclusion criteria. Median age (IQR) was 73 (62 - 79) years; TTE was performed a median (IQR) of 2 (1 - 3) days prior to surgery; mean (SD) RVSP was 56.1 (±12.4) mmHg and mean (SD) PASP was 42.1 (±14.9) mmHg. Concordance correlation coefficient between RVSP and PASP was only 0.13 (95% CI 0.02 - 0.24). On multivariate linear regression, PASP was significantly associated with RVSP and CVP (p < 0.01), but not anesthetic MAC, age or proximity of measurements. Bland-Altman bias was -13.9 mmHg; 95% limits of agreement were -48.0 to +20.1 mmHg. Conclusion: Preoperative RVSP measured by TTE correlates poorly with intraoperative PASP measured by PAC during general anesthesia.

KCNQ1 encodes the voltage-gated α-subunit of the I Ks channel complex (Kv7.1), and KCNQ1 mutations are associated with multiple arrhythmia syndromes. Over the past 12 years, hundreds of different KCNQ1 mutations have been linked to congenital long QT syndrome but only three KCNQ1 variants, each identified in only one family, are linked to familial early-onset AF (<50 years of age). The scant genetic linkage between KCNQ1 and early-onset AF raises the question as to whether these KCNQ1 variants actually cause familial early-onset AF or simply unmask a latent genetic predisposition. We now report that a single KCNQ1 variant, pArg231His or R231H, is identified in five unrelated families with a high penetrance of familial early-onset AF. Whole-cell patch clamp of cells heterologously expressing the obligatory I Ks β-subunit KCNE1 with wild-type KCNQ1 (WT) or WT and R231H (to mimic the patients’ genotypes) showed that cells co-expressing R231H increased current at negative and resting membrane potentials. Additionally, currents recorded from cells using a human atrial action potential (AP) waveform at physiological temperature showed that WT is minimally activated during the atrial AP and co-expression of R231H increases current measured during the atrial AP waveform by greater than 20-fold (WT, n = 10; WT & R231H, n = 12, p<0.0001). Simulations using a computational model of a human atrial AP also predicted that I Ks is normally minimally activated in the atria and R231H would dramatically increase I Ks and shorten the atrial AP. We conclude that KCNQ1 mutations are capable of causing familial early-onset AF by increasing I Ks during the atrial AP and shortening atrial refractoriness.

The mammalian heart loses its regenerative potential within a week after birth. Although under certain circumstances adult cardiomyocytes can re-enter the cell cycle, initiate DNA synthesis and progress towards mitosis, however, they do not complete a conventional mitosis cycle and proceed towards endomitosis resulting in polyploidy. This suggests that high-energy dependent steps in cell cycle and myofibrillar disassembly are malfunctioning in adult cardiomyocytes. It is known that nucleotide-based energetic signaling and metabolic environment are critical for initiation of tissue regeneration after injury. The regulatory mechanisms and energetic-metabolic signaling circuits that govern cardiomyocyte cell cycle withdrawal and binucleation are poorly understood. Using mouse neonatal (2 and 10 days) hearts, with high and low regenerative capacity, respectively, we have determined metabolomic profiles and dynamics of phosphotransfer circuits and AMP-signaling using 18O-phosphoryl labeling mass-spectrometric and 18O-assisted 31P NMR techniques. The results demonstrate that loss of heart regenerative capacity 10 days after birth is associated with marked changes in heart metabolome and adenylate kinase (AK)-catalyzed phosphotransfer flux. Among most altered metabolites were putrescine and myo-inositol, involved in tissue regeneration, Krebs cycle and amino acid metabolites, creatinine, glucose-6-phosphate and lactate indicating rearrangements in energy and substrate metabolic systems. AK flux was the only phosphotransfer flux significantly upregulated in hearts at 10 days of age along with increased in mitochondrial and glycolytic capacities and mitochondrial AK2 expression. Increased AK2 expression was associated with augmented AMP phosphorylation, measured by generation of β-ATP[18O], and reduction of AMPK activity. Thus, increased channeling of AMP into mitochondria and reduction of AK-AMP-AMPK signaling axis could contribute to the withdrawal from completion of cell cycle in terminally differentiated adult cardiomyocytes. The uncovered metabolic signaling mechanism opens new avenues for targeted regulation of heart regenerative potential critical for repair of injured hearts.

Introduction: Prior cardiac surgery can complicate the clinical presentation, diagnosis, and management of patients with type A aortic dissection (TAAAD). This report from the International Registry of Acute Aortic Dissection (IRAD) examines this hypothesis. Methods: 352 of 2289 TAAAD patients (15.4%) enrolled in IRAD had cardiac surgery prior to dissection, including coronary artery bypass grafting (CABG, 34.6%), aortic or mitral valve surgery (38.4%), aortic surgery (44.7%), and other cardiac surgery (18.1%). Results: Comparative differences in baseline demographics, clinical presentation, and management time are shown in Table 1. Patients with prior cardiac surgery were more likely to undergo CABG (p=0.006) or mitral valve replacement (p=0.001) at the time of dissection repair. Total cardiopulmonary bypass time was higher in patients with prior cardiac surgery (p<0.001); no difference was seen in cardiac arrest time (p=0.113) or cerebral ischemia time (p=0.286). In-hospital mortality was significantly higher for patients with prior cardiac surgery (33.5% vs. 24.0%, p70 (RR1.58, 95% CI 1.25-1.99), and medical management of acute dissection (RR 4.79, 95% CI 3.62-6.34). Kaplan-Meier analysis is shown in Figure 1. Conclusion: Prior cardiac surgery not only delays presentation and diagnosis of acute type A dissections, but is also an important adverse risk factor for early and late mortality.

Introduction- Two dimensional speckle tracking echocardiography is a novel non-invasive method to assess subtle changes in left ventricular (LV) function such as strain and rotational dynamics. Limited data exists for assessing the impact of severity of aortic stenosis (AS) on LV apical rotation Objective- To determine the impact of severity of AS on LV longitudinal strain as well as LV apical rotation in patients with preserved LV ejection fraction and various degrees of AS. Methods- We prospectively measured longitudinal LV strain and apical rotation in 74patients with preserved LV ejection fraction but no (n= 22), mild (MG 10-25 mmHg; n= 20), moderate (MG 25-40 mmHg; n= 18), or severe (MG >40 mmHg; n= 14) AS who were undergoing echocardiographic examination at our institution. Two dimensional speckle tracking method was used to obtain average peak longitudinal strain using apical 4, 2-chamber and long-axis views while apical short axis view was used to obtain the LV apical rotation. Results- Mean age between no vs. mild vs. mod vs. severe AS groups (73±11yrs; 70±13yrs; 77±6yrs; 76±14 yrs) was not different (p=0.26). Presence of hypertension (64%, 65%, 78%, 71%) and coronary artery disease (14%, 6%, 25%, 29%) were also not different between the groups (p = 0.76 and p = 0.23 respectively). Average LV peak global longitudinal strain was not different between groups (-17.5±3%; -17.5±5%;-16.6±4%; -16.6±3% (p=0.82). However LV peak apical rotation was higher with worsening severity of aortic stenosis (14.8±8°; 14.7±9°; 21.3±11°; 23.7±12°) (overall p=0.02) (Figure). Conclusions- 1) LV peak longitudinal strain was not different between patients with no stenosis when compared to patients with various levels of aortic stenosis. 2) However, LV apical rotation increases with worsening levels of AS probably to maintain the LV stroke volume. Further studies are needed to evaluate the role of LV apical rotation in deciding the timing of surgery in patients with severe AS.

Background: Stroke is one of the most dreaded complications of type A acute aortic dissection (TA-AAD). However, few data exist on its incidence and association with prognosis. Methods: We evaluated 2202 TA-AAD patients [pts, mean age 61.9 ± 14.4, 1487 (67.5%) male] from the International Registry of Acute Aortic Dissection (IRAD) to determine the incidence and prognostic influence of stroke in TA-AAD. Results: Stroke was present at arrival in 132 (6.0%) TA-AAD pts. Stroke pts were older (65±12 vs. 62±15 yrs; p=.002) and more likely to have hypertension (86% vs. 71%; p=.001) or atherosclerosis (29% vs. 22%; p=.042). While chest pain at arrival was less common (70% vs. 82%; p<.001), stroke pts presented more often with syncope (44% vs. 15%; p<.001), shock (14% vs. 7%; p=.005) or pulse deficit (51% vs. 29%; p=<.001). Arch vessels involvement was more frequent among the stroke pts (68% vs. 37%; p<.001). Stroke pts were treated less frequently by surgery (74% vs. 85%; p<.001). Hospital stay was significantly longer in patients presenting with stroke (median 17.9 versus 13.3 days, p<0.001). Stroke patients demonstrated more frequent in-hospital complications (Table) and higher mortality (adjusted OR 1.62, 95% CI .99-2.65, p=.055) Among hospital survivors, mortality at follow-up was similar in pts with and without stroke (adjusted HR 1.15, 95% CI 0.46-2.89, p=.761). Conclusions: Stroke occurred in greater than 1 of 20 pts with TA-AAD and was associated with increased morbidity and in-hospital, but not long-term mortality. Whether aggressive early intervention will reduce morbidity and improve mortality remains to be evaluated in future studies.