Research Spotlight

Alvarez Villela, M., C. Y. Guerrero-Miranda, T. Chinnadurai, S. R. Patel and U. P. Jorde (2020). “Rate Response Pacing in Left Ventricular Assist Device Patients.” ASAIO J 66(2): e29-e30.

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Chronotropic incompetence (CI) is common in advanced heart failure and is associated with worse functional capacity. This impaired heart rate (HR) response during exercise is ameliorated but persists after left ventricular assist device (LVAD) implantation. Patients with continuous flow LVAD (CF-LVAD) suffer from significant exercise limitation despite restoration of resting cardiac output. Whether CI contributes to exercise limitation in this setting is unknown. We examined the role of CI and the effect of rate response pacing (RRP) on functional capacity in a group of stable patients with LVAD . . . Our findings demonstrate the association between CI and poor functional capacity in patients with advanced heart failure and CF-LVAD, in line with one small prior study. Findings in this cohort point out the inadequacy of current RRP technologies for sensing signals other than atrial rate during different types of physical activity. When RRP increased the HR promptly and in a sustained manner, replicating the activity of the sinus node, the effect on aerobic capacity was substantial, but this occurred in only a minority of patients. In contrast to the heterogeneous effect of RRP during treadmill-based CPX, its effect on 6 MWD was more homogeneous. This could represent a difference in CIED sensing efficacy since all of the employed devices in this study have an accelerometer-based RRP system. Ambulation, producing linear displacement of the body during 6 MWT could be more easily sensed by accelerometer-based systems than the more static motion during treadmill exercise. (Excerpt from text, p. e29; no abstract available.)

Golshan, M., S. Loibl, S. M. Wong, J. B. Houber, J. O’Shaughnessy, H. S. Rugo, N. Wolmark, M. D. McKee, D. Maag, D. M. Sullivan, O. Metzger-Filho, G. Von Minckwitz, C. E. Geyer, Jr., W. M. Sikov and M. Untch (2020). “Breast Conservation After Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Surgical Results From the BrighTNess Randomized Clinical Trial.” JAMA Surg Jan 8. [Epub ahead of print].

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Importance: Neoadjuvant systemic therapy (NST) is often administered to enable breast-conserving therapy (BCT) in stages II to III breast cancer. Objectives: To prospectively evaluate the role of NST in conversion from BCT ineligibility to BCT eligibility and to assess the association of response to NST, germline BRCA (gBRCA) status, and region of treatment with surgical choice in women with triple-negative breast cancer (TNBC). Design, Setting, and Participants: This prespecified secondary analysis of a multicentered, phase 3, double-blind, randomized clinical trial (BrighTNess) enrolled 634 eligible women across 145 centers in 15 countries in North America, Europe, and Asia. Women with operable, clinical stages II to III TNBC who underwent gBRCA mutation testing before initiating NST were eligible to participate. Data were collected from April 1, 2014, to December 8, 2016. This preplanned analysis was performed from January 5, 2018, to October 28, 2019. Interventions: Study participants were randomized to receive 12 weeks of weekly paclitaxel alone or with the addition of carboplatin and/or veliparib, followed by 4 cycles of doxorubicin hydrochloride and cyclophosphamide. Main Outcomes and Measures: Surgeons assessed BCT candidacy by clinical and radiographic criteria before and after NST. Surgical choices and whether BCT eligibility was associated with the likelihood of pathologic complete response were then analyzed. Results: Among the 634 randomized patients (median age, 51 [range, 22-78] years), pre- and post-NST assessments were available for 604 patients. Of 141 patients deemed BCT ineligible at baseline, 75 (53.2%) converted to BCT eligible. Overall, 342 (68.1%) of 502 patients deemed BCT eligible after NST underwent BCT, including 42 (56.0%) of the 75 who converted to BCT eligible. Patients treated in Europe and Asia were more likely to undergo BCT (odds ratio, 2.66; 95% CI, 1.84-3.84) compared with those treated in North America. Among patients without gBRCA mutation undergoing mastectomy, those treated in North America were more likely to undergo contralateral prophylactic mastectomy (57 of 81 [70.4%] vs 6 of 30 [20.0%]; P < .001). Rates of pathologic complete response were similar between patients deemed BCT eligible at baseline and those who were BCT ineligible but converted to BCT eligibility after NST (55.3 [235 of 425] vs 49.3% [37 of 75]; P = .38). Conclusions and Relevance: This prospective analysis of NST and BCT eligibility in TNBC demonstrates a conversion from BCT ineligibility to BCT eligibility of 53.2%. Lower BCT rates among eligible patients and higher bilateral mastectomy rates among patients without gBRCA mutation in North America merit investigation. Trial Registration: ClinicalTrials.gov identifier: NCT02032277.

Golshan, M., S. M. Wong, S. Loibl, J. B. Huober, J. O’Shaughnessy, H. S. Rugo, N. Wolmark, P. Ansell, D. Maag, D. M. Sullivan, O. Metzger-Filho, G. Von Minckwitz, C. E. Geyer, Jr., W. M. Sikov and M. Untch (2020). “Early assessment with magnetic resonance imaging for prediction of pathologic response to neoadjuvant chemotherapy in triple-negative breast cancer: Results from the phase III BrighTNess trial.” Eur J Surg Oncol 46(2): 223-228.

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INTRODUCTION: The ability of breast magnetic resonance imaging (MRI) to predict pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) varies across biological subtypes. We sought to determine how well breast MRI findings following initial treatment on the phase III BrighTNess trial correlated with pCR in patients with triple negative breast cancer (TNBC). METHODS: Baseline and mid-treatment imaging and pathologic response data were available in 519 patients with stage II-III TNBC who underwent NST as per protocol. MRI complete response (mCR) was defined as disappearance of all target lesion(s) and MRI partial response (mPR) as a >/=50% reduction in the largest tumor diameter. RESULTS: Overall, mCR was demonstrated in 116 patients (22%), whereas 166 (32%) had mPR and 237 (46%) had stable/progressive disease (SD/PD). The positive predictive value (PPV), negative predictive value, and overall accuracy of the mid-treatment MRI for pCR were 78%, 56%, and 61%, respectively; accuracy did not differ significantly between gBRCA mutation carriers and non-carriers (52% vs. 63%, p=0.10). When compared to patients with SD/PD, those with mPR or mCR were 3.35-fold (95% CI 2.07-5.41) more likely to have pCR at surgery. MRI response during NST was significantly associated with eligibility for breast-conserving surgery following completion of treatment (93.1% for mCR vs. 81.6% for SD/PD, p<0.001). CONCLUSIONS: Complete response on mid-treatment MRI in the BrighTNess trial had a PPV of 78% for demonstration of pCR after completion of NST in TNBC. However, a substantial proportion of patients with mPR or SD/PD also achieved a pCR. CLINICAL TRIAL REGISTRATION: NCT02032277.

Wang, C. H., W. T. Chang, K. I. Su, C. H. Huang, M. S. Tsai, E. Chou, T. C. Lu, W. J. Chen, C. C. Lee and S. C. Chen (2020). “Neuroprognostic accuracy of blood biomarkers for post-cardiac arrest patients: A systematic review and meta-analysis.” Resuscitation 148: 108-117.

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AIM: To summarise and compare the prognostic accuracy of the blood biomarkers of brain injury, including NSE and S-100B, for neurological outcomes in adult post-cardiac arrest patients. METHODS: We systematically searched PubMed and Embase databases from their inception to March 2019. We selected studies providing sufficient data of prognostic values of NSE or S-100B to predict neurological outcomes in adult post-cardiac arrest patients. We adopted QUADAS-2 to assess risk of bias and a Bayesian bivariate random-effects meta-analysis model to synthesise the prognostic data. The study protocol was registered with PROSPERO (CRD42018084933). RESULTS: We included 42 studies involving 4806 patients in the meta-analysis. The NSE was associated with a pooled sensitivity of 0.56 (95% credible interval [CrI], 0.47-0.65) and pooled specificity of 0.99 (95% CrI, 0.98-1.00). The S-100B was associated with a pooled sensitivity of 0.63 (95% CrI, 0.46-0.78) and pooled specificity of 0.97 (95% CrI, 0.92-1.00). The heterogeneity for NSE (I(2), 22.4%) and S-100B (I(2), 16.1%) was low and publication bias was not significant. In subgroup analyses, both biomarkers were associated with high specificity across all subgroups with regard to different populations (i.e. whether patients were out-of-hospital cardiac arrest or whether patients received targeted temperature management), different timings of measurement, and different timings of outcome assessment. CONCLUSIONS: The prognostic performance was comparable between NSE and S-100B. Both biomarkers may be integrated into a multimodal neuroprognostication algorithm for post-cardiac arrest patients and institution-specific cut-off points for both biomarkers should be established.

Wang, C. H., A. F. Lee, W. T. Chang, C. H. Huang, M. S. Tsai, E. Chou, C. C. Lee, S. C. Chen and W. J. Chen (2020). “Comparing Effectiveness of Initial Airway Interventions for Out-of-Hospital Cardiac Arrest: A Systematic Review and Network Meta-analysis of Clinical Controlled Trials.” Ann Emerg Med Jan 23. [Epub ahead of print].

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STUDY OBJECTIVE: We compare effectiveness of different airway interventions during cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest. METHODS: We systematically searched the PubMed and EMBASE databases from their inception through August 2018 and selected randomized controlled trials or quasi randomized controlled trials comparing intubation, supraglottic airways, or bag-valve-mask ventilation for treating adult out-of-hospital cardiac arrest patients. We performed a network meta-analysis along with sensitivity analyses to investigate the influence of high intubation success rate on meta-analytic results. RESULTS: A total of 8 randomized controlled trials and 3 quasi randomized controlled trials were included in the network meta-analysis: 7,361 patients received intubation, 7,475 received supraglottic airway, and 1,201 received bag-valve-mask ventilation. The network meta-analysis indicated no differences among these interventions for survival or neurologic outcomes at hospital discharge. Rather, network meta-analysis suggested that supraglottic airway improved the rate of return of spontaneous circulation compared with intubation (odds ratio 1.11; 95% confidence interval 1.03 to 1.20) or bag-valve-mask ventilation (odds ratio 1.35; 95% confidence interval 1.11 to 1.63). Furthermore, intubation improved the rate of return of spontaneous circulation compared with bag-valve-mask ventilation (odds ratio 1.21; 95% confidence interval 1.01 to 1.44). The sensitivity analyses revealed that the meta-analytic results were sensitive to the intubation success rates across different out-of-hospital care systems. CONCLUSION: Although there were no differences in long-term survival or neurologic outcome among these airway interventions, these system-based comparisons demonstrated that supraglottic airway was better than intubation or bag-valve-mask ventilation and intubation was better than bag-valve-mask ventilation in improving return of spontaneous circulation. The intubation success rate greatly influenced the meta-analytic results, and therefore these comparison results should be interpreted with these system differences in mind.