Research Spotlight

Posted November 15th 2017

Acute kidney injury in cardiogenic shock: in search of early detection and clinical certainty.

Peter McCullough M.D.

Peter McCullough M.D.

Afzal, A., R. C. Vallabhan and P. A. McCullough (2017). “Acute kidney injury in cardiogenic shock: In search of early detection and clinical certainty.” Eur J Heart Fail: 1-3.

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This study stands out as the rst study to prospectively eval-uate AKI in patients with CS by KDIGO guidelines, based notonly on creatinine, but also on cystatin C.5The AKI mortal-ity results in this study are internally consistent as patients pre-senting with A KI had lower ejection fractions, higher Sequen-tial Organ Failure Assessment scores, and a higher incidenceof respiratory failure requiring mechanical ventilation.7Rates ofrenal replacement therapy were 14%, yet the 90-day mortalityrate was 38% suggesting that the majority of deaths in the rst20 days reected the natural history of CS treated with stan-dard of care in the cardiac catheterization laboratory and coro-nary care unit and were not amenable to ultraltration for pul-monary oedema/anuria or haemodialtration for hyperkalaemia orazotaemia.


Posted November 15th 2017

Early Experience with New Transcatheter Mitral Valve Replacement.

Michael J. Mack M.D.

Michael J. Mack M.D.

Bapat, V., V. Rajagopal, C. Meduri, R. S. Farivar, A. Walton, S. J. Duffy, R. Gooley, A. Almeida, M. J. Reardon, N. S. Kleiman, K. Spargias, S. Pattakos, M. K. Ng, M. Wilson, D. H. Adams, M. Leon, M. J. Mack, S. Chenoweth and P. Sorajja (2017). “Early experience with new transcatheter mitral valve replacement.” J Am Coll Cardiol: 2017 Oct [Epub ahead of print].

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BACKGROUND: Transcatheter mitral valve replacement (TMVR) is a potential therapy for patients with symptomatic, severe mitral regurgitation (MR). The feasibility of this therapy remains to be defined. OBJECTIVE: We report our early experience with TMVR using a new valve system. METHODS: The valve is a self-expanding, nitinol valve with bovine pericardial leaflets that is placed using a transapical delivery system. Patients with symptomatic MR who were deemed high or extreme risk by the local heart teams were enrolled in a global pilot study at 14 sites (U.S., Australia, and Europe). RESULTS: 50 consecutively enrolled patients (mean age, 73+/-9 years; 58.0% men; 84% secondary MR) underwent TMVR with the valve. The mean STS score was 6.4+/-5.5%; 86% of patient were NYHA class III or IV, and the mean left ventricular ejection fraction was 43+/-12%. Device implant was successful in 48 patients with a median deployment time of 14 (IQR, 12, 17) minutes. The 30-day mortality was 14%, with no disabling strokes, or repeat interventions. Median follow-up was 173 (IQR, 54, 342) days. At latest follow-up, echocardiography confirmed mild or no residual MR in all implanted patients. Improvements in symptom class (79% in NYHA I or II at follow-up; p<0.0001 vs. baseline), and Minnesota heart failure questionnaire scores (56.2+/-26.8 vs. 31.7+/-22.1; p=0.011) were observed. CONCLUSIONS: TMVR with the valve was feasible in a population at high-or extreme-risk for conventional mitral valve replacement. These results inform trial design of TMVR in lower-risk patients with severe mitral valve regurgitation.


Posted November 15th 2017

Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials.

Milton Packer M.D.

Milton Packer M.D.

Cleland, J. G. F., K. V. Bunting, M. D. Flather, D. G. Altman, J. Holmes, A. J. S. Coats, L. Manzano, J. J. V. McMurray, F. Ruschitzka, D. J. van Veldhuisen, T. G. von Lueder, M. Bohm, B. Andersson, J. Kjekshus, M. Packer, A. S. Rigby, G. Rosano, H. Wedel, A. Hjalmarson, J. Wikstrand and D. Kotecha (2017). “Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: An individual patient-level analysis of double-blind randomized trials.” Eur Heart J: 2017 Oct [Epub ahead of print].

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Aims: Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF >/= 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results: Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 >/= 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF >/= 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF >/=50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conclusion: Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.


Posted November 15th 2017

Categorizing body mass index biases assessment of the association with post-coronary artery bypass graft mortality.

James R. Edgerton M.D.

James R. Edgerton M.D.

Filardo, G., B. D. Pollock and J. Edgerton (2017). “Categorizing body mass index biases assessment of the association with post-coronary artery bypass graft mortality.” Eur J Cardiothorac Surg 52(5): 924-929.

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OBJECTIVES: The high prevalence of obesity makes accurately estimating the impact of anthropometric measures on cardiac surgery outcomes critical. The Society of Thoracic Surgeons coronary artery bypass graft (CABG) surgery risk model includes body surface area (as a continuous variable, using spline functions), but most studies apply various categorizations of body mass index (BMI)-contributing to the contradictory published findings. We assessed the association between BMI (modelled as a continuous variable without assumptions of linearity) and CABG operative mortality and examined the impact of applying previous studies’ BMI modelling strategies. METHODS: We identified 25 studies investigating the BMI-operative mortality association: 22 categorized BMI, 2 as a linear continuous variable,1 used spline functions. Our cohort of 12 715 consecutive patients underwent isolated CABG at 32 cardiac surgery programmes in North Texas from 1 January 2008-31 December 2012. BMI was modelled using restricted cubic spline functions in a propensity-adjusted model (controlling for Society of Thoracic Surgeons risk factors) estimating operative mortality. The analysis was repeated using each categorization identified and modelling BMI as a linear continuous variable. RESULTS: BMI (modelled with a restricted cubic spline) was significantly associated with operative mortality (P < 0.0001). Risk was lowest for BMI near 30 kg/m2 and highest below 20 kg/m2 and above 40 kg/m2. No categorization, nor the linear continuous model, fully captured this association. CONCLUSIONS: BMI is strongly associated with CABG operative mortality. Categorizing BMI (or assuming a linear relationship) heavily biases estimates of its association with post-CABG mortality. In general, smoothing techniques should be used for all continuous risk factors to avoid bias.


Posted November 15th 2017

ACR Appropriateness Criteria® Chronic Liver Disease.

Sumeet K. Asrani M.D.

Sumeet K. Asrani M.D.

Horowitz, J. M., I. R. Kamel, H. Arif-Tiwari, S. K. Asrani, N. M. Hindman, H. Kaur, M. M. McNamara, R. B. Noto, A. Qayyum and T. Lalani (2017). “Acr appropriateness criteria(r) chronic liver disease.” J Am Coll Radiol 14(11s): S391-s405.

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Because liver fibrosis can be treated, it is important to diagnose liver fibrosis noninvasively and monitor response to treatment. Although ultrasound (grayscale and Doppler) can diagnose cirrhosis, it does so unreliably using morphologic and sonographic features and cannot diagnose the earlier, treatable stages of hepatic fibrosis. Transient elastography, ultrasound elastography with acoustic radiation force impulse, and MR elastography are modalities that can assess for hepatic fibrosis. Although all international organizations recommend ultrasound for screening for hepatocellular carcinoma, ultrasound is particularly limited for identifying hepatocellular carcinoma in patients with obesity, nonalcoholic fatty liver disease, and nodular cirrhotic livers. In these patient groups as well as patients who are on the liver transplant wait list, ultrasound is so limited that consideration can be made for screening for hepatocellular carcinoma with either MRI or multiphase CT. Additionally, patients who have been previously diagnosed with and treated for hepatocellular carcinoma require continued surveillance for recurrent hepatocellular carcinoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.