Evaluation of the incidence, timing, and potential recovery rates of complete atrioventricular block after transcatheter aortic valve implantation: a Japanese multicenter registry study.

Data on the accurate onset date and serial changes of the complete atrioventricular block (CAVB) after transcatheter aortic valve implantation (TAVI) are limited. This study aimed to assess the incidence, timing, and potential recovery of CAVB following TAVI. Total 696 patients who underwent TAVI were enrolled. Acute CAVB was evaluated within 24 h; delayed CAVB was evaluated 24 h after TAVI. Recovered CAVB was defined as ventricular pacing < 1% during the follow-up or transit block without the need for permanent pacemaker implantation (PMI). The other patients with CAVB were categorized as continued CAVB. Clinical differences between the recovered and continued CAVB groups were evaluated, and the predictive factors of continued CAVB were assessed. The incidence rates of CAVB, acute CAVB, and delayed CAVB were 6.9% (48/696), 4.6% (32/696), and 2.3% (16/696), respectively. Overall, 47.9% (23/48) of patients had recovered CAVB, which was more prevalent in the acute CAVB group than in the delayed CAVB group [59.4% (19/32) vs. 25.0% (4/16), p = 0.025]. CAVB recovery occurred within 24 h (61.0%, 14/23) and after 24 h (39.0%, 9/23). Before CAVB recovery, 21.7% (5/23) of patients had already undergone PMI. A pre-existing complete right bundle branch block (CRBBB) was the only independent predictive factor of continued CAVB (odds ratio 4.51, 95% confidence interval 1.03-19.6, p = 0.045). In conclusion, a pre-existing CRBBB and the timing and prolonged duration of CAVB may be used in risk stratification to determine the appropriateness of early discharge, optimal PMI date, and PMI indication.

Current status of hybrid intravascular ultrasound and optical coherence tomography catheter for coronary imaging and percutaneous coronary intervention.

Both intravascular ultrasound (IVUS) and optical coherence tomography (OCT) play a crucial role in elucidating the pathophysiology of coronary artery disease (CAD) with the goal to improve patient outcomes of medical and/or interventional CAD management. However, no single intravascular imaging technique has been proven to provide complete and detailed evaluation of all CAD lesions due to some limitations. Although sequential use of multiple modalities may sometimes be performed, there may be issues related to risk, time, and cost. To overcome these problems, several hybrids involving dual-probe combined IVUS-OCT catheters have been developed. The aim of this review article is to demonstrate some limitations of stand-alone imaging devices for evaluation of CAD, summarize the advances in hybrid IVUS-OCT imaging devices, discuss the technical challenges, and present the potential value in the clinical setting, especially in patients receiving medical or interventional CAD management.

Impact of pre-procedural hyponatremia on clinical outcomes after transcatheter aortic valve replacement: A propensity-matched analysis.

BACKGROUND: Hyponatremia is associated with the increased risk of early and late mortality in patients with cardiac disease. This study aimed to assess the prognostic value of hyponatremia in patients who had undergone transcatheter aortic valve replacement (TAVR). METHODS: We investigated 1,215 consecutive patients (mean age: 84.4 ± 5.0 years) who underwent TAVR using data from the Optimized CathEter vAlvular iNtervention (OCEAN)-TAVR Japanese multicenter registry. Hyponatremia was defined as a serum sodium value less than 135 mEq/L. The baseline characteristics, procedural outcomes, all-cause, cardiovascular, and non-cardiovascular mortality were compared between patients with hyponatremia (n = 106, 8.7%) and without hyponatremia (n = 1,109, 91.3%). A propensity-matching analysis was used to adjust for the non-uniform patient characteristics. RESULTS: Differences in the baseline characteristics were observed between the two groups regarding the prevalence of pulmonary disease (37.7% vs. 28.9%, P = 0.04) and the performance of non-elective TAVR (10.4% vs. 4.2%, P = 0.01), although these were minimized in the matched model. The 30-day mortality rates differed between the two groups (7.6% vs. 1.4%, P < 0.001). During a mean follow-up of 330 days, the all-cause and cardiovascular mid-term mortality were higher in the hyponatremia group than in the non-hyponatremia group (log-rank test: P = 0.0047, and P < 0.001, respectively). The three findings above were not attenuated in the propensity-matched model (P < 0.001, P = 0.0044, and P = 0.014, respectively). In contrast, there was no difference in non-cardiovascular mortality between the two groups in both the overall and matched model (P = 0.40 and P = 0.13, respectively). CONCLUSIONS: Pre-procedural hyponatremia may be a useful marker for predicting early and mid-term clinical outcomes after TAVR.

Impact of frailty markers on outcomes after transcatheter aortic valve replacement: insights from a Japanese multicenter registry.

There are no standardized criteria for measuring patients' frailty. We examined prognosis based on four frailty markers [serum albumin level, grip strength, gait speed, and clinical frailty scale (CFS)] in patients who underwent transcatheter aortic valve replacement (TAVR) between October 2013 and April 2016 and were recorded in the Optimized CathEter vAlvular iNtervention (OCEAN) Japanese multicenter registry. Serum albumin level was assessed by dividing patients into two groups: hypoalbuminemia or non-hypoalbuminemia according to their serum albumin level. Clinical outcomes including all-cause, cardiovascular and non-cardiovascular mortality rates after TAVR were compared. During the follow-up period cumulative all-cause, cardiovascular and non-cardiovascular mortality rates were significantly higher in the hypoalbuminemia group than in the non-hypoalbuminemia group. This result remained unchanged even after a propensity-matched model was used in terms of cumulative all-cause and non-cardiovascular mortality; however, differences in cardiovascular mortality rates were attenuated. To consider the impact of grip strength patients were divided into a low or high peak grip strength group based on classification and regression tree (CART) survival analysis. The clinical outcomes for each sex were compared between the two groups. In both sexes the cumulative 1-year mortality rates were significantly different between the two groups. To investigate gait speed patients were classified into two gait speed groups (low or high gait speed group) based on CART survival analysis. Clinical outcomes were compared between the two groups. The cumulative 1-year mortality rate was significantly different between the two gait speed groups. The effect of CFS on prognosis after TAVR was assessed. Patients were categorized into five groups based on the following CFS scores: CFS1-3, CFS4, CFS5, CFS6, and CFS ≥7. We evaluated the relationship between the CFS score and other indicators of frailty markers. We also assessed the mid-term mortality among the five groups. The CFS score had a significant correlation with other frailty markers. The cumulative 1-year mortality increased with an increasing CFS score. In the Cox regression multivariable analysis, the CFS score was an independent predictive factor of an increased late cumulative mortality risk. In conclusion, the results suggest that serum albumin level, grip strength, gait speed, and CFS score are all useful indicators when considering the optimal indications and risk stratification for TAVR.

Gait Speed Can Predict Advanced Clinical Outcomes in Patients Who Undergo Transcatheter Aortic Valve Replacement: Insights From a Japanese Multicenter Registry.

BACKGROUND: Gait speed reflects an important factor of frailty and is associated with an increased risk of late mortality in patients with cardiac disease. This study sought to assess the prognostic value of gait speed in elderly patients who underwent transcatheter aortic valve replacement. METHODS AND RESULTS: We investigated the 5-m or 15-feet gait speed (m/sec) in 1256 patients who underwent transcatheter aortic valve implantation using data from the OCEAN-TAVI Japanese multicenter registry (Optimized Catheter Valvular Intervention-Transcatheter Aortic Valve Implantation). Baseline characteristics, procedural outcomes, and all-cause mortality were compared among groups defined by differential gait speed classification: model 1, normal (>0.83 m/sec; n=563; 44.8%), slow (0.5-0.83 m/sec; n=429; 34.2%), slowest (<0.83 m/sec; n=205; 16.3%), unable to walk (n=48; 3.8%); and model 2, classification and regression tree survival model indicating the threshold of gait speed as 0.385 m/sec (>0.385 m/sec; n=1080 versus ≤0.385 m/sec; n=117). The cumulative 1-year mortality rate showed significant differences in the classical gait speed groups in model 1 (7.6%, 6.6%, 18.2%, and 40.7%, respectively; P<0.001) and survival classification and regression tree group in model 2 (7.7% versus 21.9%; P<0.001). The slowest walkers and those unable to walk demonstrated independent associations with increased midterm mortality after adjustment for several confounding factors (hazard ratio, 1.83, 4.28; 95% confidence interval, 1.03-3.26, 2.22-8.72; P=0.039, <0.001, respectively). Gait speed <0.385 m/sec determined by classification and regression tree also independently associated with worse prognosis (hazard ratio, 2.40; 95% confidence interval, 1.75-5.88; P=0.001). CONCLUSIONS: Gait speed using both traditional and specific classification is useful as a potential marker for predicting vulnerable patients associated with adverse clinical outcomes after transcatheter aortic valve replacement.

The incidence, predictive factors and prognosis of acute pulmonary complications after transcatheter aortic valve implantation.

OBJECTIVES: Although acute pulmonary complications (APCs), such as the exacerbation of pulmonary disease (PD) or a newly developed pulmonary event, are thought to be catastrophic after invasive therapy, little is known about the occurrence of APCs after transcatheter aortic valve implantation (TAVI). This study aims to clarify the incidence, predictive factors and impact of APCs on prognosis after TAVI. METHODS: We identified 749 patients who underwent TAVI, using data from the Optimized CathEter vAlvular iNtervention (OCEAN-TAVI) Japanese multicentre registry. APCs were defined as exacerbation of a comorbidity or newly developed PD during hospitalization. Patients were divided into 2 groups: an APC group (1.5%, 11/749) and a non-APC group (98.5%, 738/749). Clinical and prognostic outcomes were compared, and predictive factors for APCs were assessed. RESULTS: Procedure-related death did not differ between the groups (0.4% vs 0.0%, P = 1.00), although 30-day mortality was significantly higher in the APC group than in the non-APC group (27.3% vs 1.6%, P = 0.001) and the difference in cumulative 1-year mortality increased further (72.7% vs 8.6%, log-rank test: P < 0.001). In particular, concomitant PD and transapical (TA) approach were identified as predictors of APCs after TAVI [univariable odds ratio (uOR) = 24.2, 95% confidence interval (CI) = 3.08-189.9, P = 0.002; uOR = 3.69, 95% CI = 1.11-12.3, P = 0.033, respectively]. CONCLUSIONS: Although rare, the occurrence of APCs after TAVI was associated with extremely poor prognosis. Patients undergoing TAVI with concomitant PD and/or TA require careful consideration to avoid the risk of APCs.

Impact of the Clinical Frailty Scale on Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: The semiquantitative Clinical Frailty Scale (CFS) is a simple tool to assess patients' frailty and has been shown to correlate with mortality in elderly patients even when evaluated by nongeriatricians. The aim of the current study was to determine the prognostic value of CFS in patients who underwent transcatheter aortic valve replacement. METHODS: We utilized the OCEAN (Optimized Catheter Valvular Intervention) Japanese multicenter registry to review data of 1215 patients who underwent transcatheter aortic valve replacement. Patients were categorized into 5 groups based on the CFS stages: CFS 1-3, CFS 4, CFS 5, CFS 6, and CFS ≥7. We subsequently evaluated the relationship between CFS grading and other indicators of frailty, including body mass index, serum albumin, gait speed, and mean hand grip. We also assessed differences in baseline characteristics, procedural outcomes, and early and midterm mortality among the 5 groups. RESULTS: Patient distribution into the 5 CFS groups was as follows: 38.0% (CFS 1-3), 32.9% (CFS4), 15.1% (CFS 5), 10.0% (CFS 6), and 4.0% (CFS ≥7). The CFS grade showed significant correlation with body mass index (Spearman's ρ=-0.077, P=0.007), albumin (ρ=-0.22, P<0.001), gait speed (ρ=-0.28, P<0.001), and grip strength (ρ=-0.26, P<0.001). Cumulative 1-year mortality increased with increasing CFS stage (7.2%, 8.6%. 15.7%, 16.9%, 44.1%, P<0.001). In a Cox regression multivariate analysis, the CFS (per 1 category increase) was an independent predictive factor of increased late cumulative mortality risk (hazard ratio, 1.28; 95% confidence interval, 1.10-1.49; P<0.001). CONCLUSIONS: In addition to reflecting the degree of frailty, the CFS was a useful marker for predicting late mortality in an elderly transcatheter aortic valve replacement cohort.

Comparative data of single versus double proglide vascular preclose technique after percutaneous transfemoral transcatheter aortic valve implantation from the optimized catheter valvular intervention (OCEAN-TAVI) japanese multicenter registry.

OBJECTIVES: This study aimed to assess the feasibility of percutaneous arterial access site closure after percutaneous transfemoral transcatheter aortic valve implantation (TF-TAVI) using single versus double Perclose ProGlide devices. BACKGROUNDS: Although suturing with the preclose technique has been widely adopted during TF-TAVI, the optimal vascular closure strategy is still under debate. METHODS: Data from 279 patients who underwent TF-TAVI, obtained from the Optimized CathEter vAlvular iNtervention (OCEAN-TAVI) Japanese multicenter registry. Technical, procedural, and clinical outcomes were compared between the single ProGlide group (n = 99) and double ProGlide group (n = 180). They were also analyzed by propensity adjusted matching model (single [n = 69] vs. double [n = 69]). All patients were treated through a 16-Fr to 20-Fr eSheath. Technical success of the closure device was defined as hemostasis not requiring alternative invasive treatment. Access site-related vascular complications, bleedings, and other procedural complications were defined according to the Valvular Academic Research Consortium-2 (VARC-2) criteria. RESULTS: The rates of technical success and access site-related vascular complications were similar in the 2 groups (94.9% vs. 91.6%, p = 0.44; 5.0% vs. 7.7%, p = 0.54, respectively). The prevalence of bleeding complications did not differ between the 2 groups (1.0% vs. 3.3%, p = 0.43). Thirty-day mortality rate also showed no difference between the 2 groups (2.0% vs. 1.1%, p = 0.95), although these events were not associated with access site failure. These results were not attenuated in the propensity matching model. CONCLUSIONS: Vascular closure with a single ProGlide in TF-TAVI could achieve equivalent, acceptable rates of technical success and procedural complications compared with the double ProGlide technique. © 2016 Wiley Periodicals, Inc.

Prognostic Value of Hypoalbuminemia After Transcatheter Aortic Valve Implantation (from the Japanese Multicenter OCEAN-TAVI Registry).

Hypoalbuminemia, a frailty criterion, belongs to a group of co-morbidities not captured as a traditional risk factor. We assessed its prognostic value in patients who underwent transcatheter aortic valve implantation (TAVI). The study included 1,215 consecutive patients from the Optimized Catheter Valvular Intervention -TAVI Japanese multicenter registry. Hypoalbuminemia was defined as serum albumin level <3.5 g/dl. Baseline characteristics, procedural outcomes, and all-cause, cardiovascular and noncardiovascular mortality rates after TAVI were compared between patients with albumin level <3.5 g/dl (hypo[h]-ALB group, n = 284) and those with albumin level >3.5 g/dl (nonhypo[nh]-ALB group, n = 931). Several baseline characteristics differed significantly between both groups, including age (85.1 ± 5.1 vs 84.2 ± 4.9 years, p = 0.012), ejection fraction (58.5 ± 14.3% vs 62.9 ± 12.4%, p <0.001), baseline kidney function, or liver disease. The 30-day mortality rate in all patients showed significant differences between the 2 groups (3.9% vs 1.3%, p = 0.005). During a mean follow-up of 330 days, cumulative all-cause, cardiovascular, and noncardiovascular mortality rates were significantly higher in the hALB group than in the nhALB group (log-rank test, p <0.001, p = 0.0021, and p <0.001, respectively). The groups were also analyzed using a propensity matching model for adjusting the baseline differences. The analysis revealed that the poorer prognosis of the hALB group in terms of cumulative all-cause and noncardiovascular mortality was retained (p = 0.038, and p = 0.0068, respectively); however, differences in cardiovascular mortality rates in the 2 groups were attenuated (p = 0.93). In conclusion, hypoalbuminemia was associated with poor prognosis, highlighted by the increase in noncardiovascular mortality. Baseline albumin level could be a useful marker for risk stratification before TAVI.

Impact of preparatory coronary protection in patients at high anatomical risk of acute coronary obstruction during transcatheter aortic valve implantation.

BACKGROUND: This study aimed to assess the effectiveness of preparatory coronary protection (CP) in patients considered at high risk of acute coronary obstruction (ACO) after transcatheter aortic valve implantation (TAVI). METHODS: The Optimized CathEter vAlvular iNtervention (OCEAN-TAVI) Japanese multicenter registry enrolled 666 consecutive patients. All patients were assessed by preprocedural multidetector computed tomography. CP using a guide wire with or without a balloon was prospectively performed according to the following criteria: 1) coronary height length from the annulus <10mm, 2) evidence of ACO during balloon aortic valvuloplasty with simultaneous aortic injection, and 3) shallow valsalva or bulky calcification on the leaflet. The incidence of ACO and other procedural outcomes were compared between the CP and non-CP groups. RESULTS: CP was performed in 14.1% of all patients (94/666). ACO had an incidence of 1.5% (10/666) and mainly occurred in women (70%) and the left coronary artery (70%). The ACO rate was significantly higher in the CP group than in the non-CP group (7.4% [7/94] vs. 0.5% [3/572]; p<0.001), although notably 30% of ACO were occurred in non-CP group. All 10 ACO cases were successfully treated by catheter intervention, although periprocedural myocardial injury occurred in 42.9% of patients with CP group and 33.3% of those without CP group. Mortality and other periprocedural complications did not significantly differ between the 2 groups. CONCLUSION: The preparatory CP strategy was feasible for the management of ACO during TAVI, but the complication of ACO was difficult to predict completely.

Impending rupture of saphenous vein graft aneurysm with floating fractured bare metal stent treated by coil embolization and covered stent implantation.

Aneurysmal degeneration of a saphenous vein graft (SVG) is a rare, but potentially fatal complication of coronary artery bypass graft (CABG) surgery. In this case report, a patient that had undergone prior CABG surgery and bare metal stent (BMS) implantation at the site of a stenotic SVG lesion presented at our hospital with chest pain, and an SVG aneurysm was detected at the previous BMS implantation site. In addition, the implanted BMS was fractured and floating in the SVG aneurysm. The SVG aneurysm was successfully occluded by percutaneous intervention, using a combination of distal covered stent deployment at the site of the anastomosis between the native coronary artery and the SVG and proximal coil embolization of the aneurysm.

Usefulness of routine aortic valve calcium score measurement for risk stratification of aortic stenosis and coronary artery disease in patients scheduled cardiac multislice computed tomography.

OBJECTIVES: This study sought to investigate the clinical utility of aortic valve calcium score (AVCS) determined by using cardiac multislice computed tomography (MSCT). METHODS: Data of 1315 consecutive patients who underwent both conventional echocardiography and MSCT were reviewed. Degree of aortic stenosis (AS) was assessed according to mean pressure gradient (mPG) measured by echocardiography. Extent of coronary artery disease (CAD) derived by MSCT also was evaluated in 1173 patients who did not undergo prior coronary treatment. Both AVCS and coronary calcium score (CCS) were defined by Agatston units (AU) according to MSCT findings. RESULTS: A total of 613 of 1315 patients were defined as AVCS positive (mean, 100 AU [range, 31.0-380.0 AU]). AVCS showed significant correlations with mPG (Spearman's ρ = 0.81, p < 0.001), and CCS (ρ = 0.53, p < 0.001). Differential adequate cut-off values of AVCS were proved for predicting severe AS with mPG ≥ 40 mmHg (1596.5 AU; AUC, 0.88; sensitivity, 89.7%; specificity, 77.0%), and for predicting moderate AS with mPG ≥ 20 mmHg (886.5 AU; area under the curve [AUC], 0.91; sensitivity, 92.4%; specificity, 78.3%). Mean AVCS was higher with increased extent of CAD (none, 0 AU [range, 0-30 AU]; single vessel, 8.5 AU [range, 0-104 AU]; multivessel, 142 AU [range, 10-525 AU]; p < 0.001). The optimal cut-off value of AVCS for predicting multivessel disease was 49 AU (AUC, 0.77; sensitivity, 68.8%; specificity, 78.0%). CONCLUSIONS: AVCS might be a surrogate marker not only for AS grading but also for CAD progression. Therefore, routine AVCS assessment could be useful for risk stratification.

ACF7 regulates cytoskeletal-focal adhesion dynamics and migration and has ATPase activity.

Coordinated interactions between microtubule (MT) and actin cytoskeletons are involved in many polarized cellular processes. Spectraplakins are enormous (>500 kDa) proteins able to bind both MTs and actin filaments (F-actin) directly. To elucidate the physiological significance and functions of mammalian spectraplakin ACF7, we've conditionally targeted it in skin epidermis. Intriguingly, ACF7 deficiency compromises the targeting of microtubules along F-actin to focal adhesions (FAs), stabilizes FA-actin networks, and impairs epidermal migration. Exploring underlying mechanisms, we show that ACF7's binding domains for F-actin, MTs, and MT plus-end proteins are not sufficient to rescue the defects in FA-cytoskeletal dynamics and migration functions of ACF7 null keratinocytes. We've uncovered an intrinsic actin-regulated ATPase domain in ACF7 and demonstrate that it is both functional and essential for these roles. Our findings provide insight into the functions of this important cytoskeletal crosslinking protein in regulating dynamic interactions between MTs and F-actin to sustain directional cell movement.

Diagnostic accuracy of coronary in-stent restenosis using 64-slice computed tomography: comparison with invasive coronary angiography.

OBJECTIVES: This study sought to evaluate the diagnostic accuracy of coronary binary in-stent restenosis (ISR) with angiography using 64-slice multislice computed tomography coronary angiography (CTCA) compared with invasive coronary angiography (ICA). BACKGROUND: A noninvasive detection of ISR would result in an easier and safer way to conduct patient follow-up. METHODS: We performed CTCA in 81 patients after stent implantation, and 125 stented lesions were scanned. Two sets of images were reconstructed with different types of convolution kernels. On CTCA, neointimal proliferation was visually evaluated according to luminal contrast attenuation inside the stent. Lesions were graded as follows: grade 1, none or slight neointimal proliferation; grade 2, neointimal proliferation with no significant stenosis (<50%); grade 3, neointimal proliferation with moderate stenosis (> or =50%); and grade 4, neointimal proliferation with severe stenosis (> or =75%). Grades 3 and 4 were considered binary ISR. The diagnostic accuracy of CTCA compared with ICA was evaluated. RESULTS: By ICA, 24 ISRs were diagnosed. Sensitivity, specificity, positive predictive value, and negative predictive value were 92%, 81%, 54%, and 98% for the overall population, whereas values were 91%, 93%, 77%, and 98% when excluding unassessable segments (15 segments, 12%). For assessable segments, CTCA correctly diagnosed 20 of the 22 ISRs detected by ICA. Six lesions without ISR were overestimated as ISR by CTCA. As the grade of neointimal proliferation by CTCA increases, the median value of percent diameter stenosis increased linearly. CONCLUSIONS: Binary ISR can be excluded with high probability by CTCA, with a moderate rate of false-positive results.

Antigenic divergence suggested by correlation between antigenic variation and pulsed-field gel electrophoresis profiles of Bordetella pertussis isolates in Japan.

Antigenic divergence has been found between Bordetella pertussis vaccine strains and circulating strains in several countries. In the present study, we analyzed B. pertussis isolates collected in Japan from 1988 to 2001 using pulsed-field gel electrophoresis (PFGE) and sequencing of two virulence-associated proteins. The 107 isolates were classified into three major groups by PFGE analysis; 87 (81%) were type A, 19 (18%) were type B, and 1 (1%) was type C. Sequence analysis of the S1 subunit of pertussis toxin (ptxS1) and adhesion pertactin (prn) genes revealed the presence of two (ptxS1A and ptxS1B) and three (prn1, prn2, and prn3) variants, respectively, in the isolates. Among those isolates, 82 (95%) of the 87 type A strains and the type C strain had the same combination of ptxS1B and prn1 alleles (ptxS1B/prn1) as the Japanese vaccine strain. On the other hand, 17 (90%) of 19 type B strains had an allele (ptxS1A/prn2) distinct from that of the vaccine strain. A correlation was found between the antigenic variation and the PFGE profile in the isolates. In addition, the frequency of the type B strain was 0, 27, 0, 42, and 37% of the isolates in the periods 1988 to 1993, 1994 to 1995, 1996 to 1997, 1998 to 1999, and 2000 to 2001, respectively. In contrast, the number of reported pertussis-like and pertussis cases decreased gradually from 1991 on, suggesting that the antigenic divergence did not affect the efficacy of pertussis vaccination in Japan.

Coordinating cytoskeletal tracks to polarize cellular movements.

For many years after the discovery of actin filaments and microtubules, it was widely assumed that their polymerization, organization, and functions were largely distinct. However, in recent years it has become increasingly apparent that coordinated interactions between microtubules and filamentous actin are involved in many polarized processes, including cell shape, mitotic spindle orientation, motility, growth cone guidance, and wound healing. In the past few years, significant strides have been made in unraveling the intricacies that govern these intertwined cytoskeletal rearrangements.

ACF7: an essential integrator of microtubule dynamics.

ACF7 is a member of the spectraplakin family of cytoskeletal crosslinking proteins possessing actin and microtubule binding domains. Here, we show that ACF7 is an essential integrator of MT-actin dynamics. In endodermal cells, ACF7 binds along microtubules but concentrates at their distal ends and at cell borders when polarized. In ACF7's absence, microtubules still bind EB1 and CLIP170, but they no longer grow along polarized actin bundles, nor do they pause and tether to actin-rich cortical sites. The consequences are less stable, long microtubules with skewed cytoplasmic trajectories and altered dynamic instability. In response to wounding, ACF7 null cultures activate polarizing signals, but fail to maintain them and coordinate migration. Rescue of these defects requires ACF7's actin and microtubule binding domains. Thus, spectraplakins are important for controlling microtubule dynamics and reinforcing links between microtubules and polarized F-actin, so that cellular polarization and coordinated cell movements can be sustained.