Research Spotlight

Biviano, A. B., T. Nazif, J. Dizon, H. Garan, J. Fleitman, D. Hassan, S. Kapadia, V. Babaliaros, K. Xu, R. Parvataneni, J. Rodes-Cabau, W. Y. Szeto, W. F. Fearon, D. Dvir, T. Dewey, M. Williams, M. J. Mack, J. G. Webb, D. C. Miller, C. R. Smith, M. B. Leon and S. Kodali (2016). “Atrial Fibrillation Is Associated With Increased Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights From the Placement of Aortic Transcatheter Valve (PARTNER) Trial.” Circ Cardiovasc Interv 9(1): e002766.

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BACKGROUND: This study sought to evaluate the impact of atrial fibrillation (AF) on clinical outcomes in patients undergoing transcatheter aortic valve replacement. METHODS AND RESULTS: Data were evaluated in 1879 patients with baseline and discharge ECGs who underwent transcatheter aortic valve replacement in the Placement of AoRTic TraNscathetER Valve (PARTNER) trial. A total of 1262 patients manifested sinus rhythm (SR) at baseline/SR at discharge, 113 SR baseline/AF discharge, and 470 AF baseline/AF discharge. Patients who converted from SR to AF by discharge had the highest rates of all-cause mortality at 30 days (P<0.0001 across all groups; 14.2% SR/AF versus 2.6% SR/SR; adjusted hazard ratio [HR]=3.41; P=0.0002) and over 2-fold difference at 1 year (P<0.0001 across all groups; 35.7% SR/AF versus 15.8% SR/SR; adjusted HR=2.14; P<0.0001). The presence of AF on baseline or discharge ECG was a predictor of 1-year mortality (adjusted HR=2.14 for SR/AF group and HR=1.88 for AF/AF groups; P<0.0001 for both groups versus SR/SR). For patients discharged in AF, those with lower ventricular response (ie, <90 bpm) experienced less 1-year all-cause mortality (HR=0.74; P=0.04). CONCLUSIONS: After transcatheter aortic valve replacement, the presence of AF at discharge, and particularly, the conversion to AF by discharge and higher ventricular response are associated with increased mortality. These data underscore the deleterious impact of AF, as well as the need for targeted interventions to improve clinical outcomes, in patients undergoing transcatheter aortic valve replacement. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Alfredsson, J., A. Stebbins, J. M. Brennan, R. Matsouaka, J. Afilalo, E. D. Peterson, S. Vemulapalli, J. S. Rumsfeld, D. Shahian, M.J. Mack and K. P. Alexander (2016). “Gait Speed Predicts 30-Day Mortality Following Transcatheter Aortic Valve Replacement: Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.” Circulation. Feb 26. [Epub ahead of print].

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BACKGROUND: -Surgical risk scores do not include frailty assessments (e.g., gait speed), which are of particular importance for severe aortic stenosis patients considering transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: -We assessed the association of 5-meter gait speed with outcomes in a cohort of 8039 patients who underwent TAVR (11/2011-06/2014) and were registered in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry (STS/ACCTVT Registry). We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for STS-predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The median gait speed was 0.63 m/s (0.47-0.79), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5 to 0.83 m/s) 48%, and normal walkers (>0.83 m/s) 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for slowest, slow, and normal walkers, respectively (p<0.001). Each 0.2 m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio 1.11, 95% confidence interval 1.01-1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio 1.35, 95% confidence interval 1.01-1.80), significantly longer hospital stays, and a lower probability of being discharged to home. CONCLUSIONS: -Gait speed is independently associated with 30-day mortality following TAVR. Identification of frail patients with the slowest gait speeds facilitates pre-procedural evaluation and anticipation of a higher level of post-procedural care. Clinical Trial Registration Information-ClinicalTrials.gov. Identifier: NCT01737528.

Ammar, M., C. T. Jordan, L. Cao, E. Lim, C. Bouchlaka Souissi, A. Jrad, I. Omrane, S. Kouidhi, I. Zaraa, H. Anbunathan, M. Mokni, N. Doss, E. Guttman-Yassky, A. B. El Gaaied, A. Menter and A. M. Bowcock (2016). “CARD14 alterations in Tunisian patients with psoriasis and further characterization in European cohorts.” Br J Dermatol 174(2): 330-337.

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BACKGROUND: Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. OBJECTIVES: To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. METHODS: CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis (GPP). Novel variants were evaluated for their effect on nuclear factor (NF)-kappaB signalling. RESULTS: Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-kappaB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-kappaB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. CONCLUSIONS: These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations.

Pascoe, V. L., A. Z. Fenves, J. Wofford, J. M. Jackson, A. Menter and A. B. Kimball (2016). “The spectrum of nephrocutaneous diseases and associations: Inflammatory and medication-related nephrocutaneous associations.” J Am Acad Dermatol 74(2): 247-270.

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There are a significant number of dermatoses associated with renal abnormalities and disease, and dermatologists need to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations and recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae. Part II of this 2-part continuing medical education article addresses inflammatory and medication-related nephrocutaneous associations.

Wang, A., P. Grayburn, J. A. Foster, M. L. McCulloch, V. Badhwar, J. S. Gammie, S. P. Costa, R. M. Benitez, M. J. Rinaldi, V. H. Thourani and R. P. Martin (2016). “Practice gaps in the care of mitral valve regurgitation: Insights from the American College of Cardiology mitral regurgitation gap analysis and advisory panel.” Am Heart J 172: 70-79.

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BACKGROUND: The revised 2014 American College of Cardiology (ACC)/American Heart Association valvular heart disease guidelines provide evidenced-based recommendations for the management of mitral regurgitation (MR). However, knowledge gaps related to our evolving understanding of critical MR concepts may impede their implementation. METHODS: The ACC conducted a multifaceted needs assessment to characterize gaps, practice patterns, and perceptions related to the diagnosis and treatment of MR. A key project element was a set of surveys distributed to primary care and cardiovascular physicians (cardiologists and cardiothoracic surgeons). Survey and other gap analysis findings were presented to a panel of 10 expert advisors from specialties of general cardiology, cardiac imaging, interventional cardiology, and cardiac surgeons with expertise in valvular heart disease, especially MR, and cardiovascular education. The panel was charged with assessing the relative importance and potential means of remedying identified gaps to improve care for patients with MR. RESULTS: The survey results identified several knowledge and practice gaps that may limit implementation of evidence-based recommendations for MR care. Specifically, half of primary care physicians reported uncertainty regarding timing of intervention for patients with severe primary or functional MR. Physicians in all groups reported that quantitative indices of MR severity were frequently not reported in clinical echocardiographic interpretations, and that these measurements were not consistently reviewed when provided in reports. In the treatment of MR, nearly 30% of primary care physician and general cardiologists did not know the volume of mitral valve repair surgeries by their reference cardiac surgeons and did not have a standard source to obtain this information. After review of the survey results, the expert panel summarized practice gaps into 4 thematic areas and offered proposals to address deficiencies and promote better alignment with the 2014 ACC/American Heart Association valvular disease guidelines. CONCLUSION: Important knowledge and skill gaps exist that may impede optimal care of the patient with MR. Focused educational and practice interventions should be developed to reduce these gaps.