Optimization of Evidence-Based Heart Failure Medications After an Acute Heart Failure Admission: A Secondary Analysis of the STRONG-HF Randomized Clinical Trial.

Importance: The Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies (STRONG-HF) trial strived for rapid uptitration aiming to reach 100% optimal doses of guideline-directed medical therapy (GDMT) within 2 weeks after discharge from an acute heart failure (AHF) admission. Objective: To assess the association between degree of GDMT doses achieved in high-intensity care and outcomes. Design, Setting, and Participants: This was a post hoc secondary analysis of the STRONG-HF randomized clinical trial, conducted from May 2018 to September 2022. Included in the study were patients with AHF who were not treated with optimal doses of GDMT before and after discharge from an AHF admission. Data were analyzed from January to October 2023. Interventions: The mean percentage of the doses of 3 classes of HF medications (renin-angiotensin system inhibitors, ß-blockers, and mineralocorticoid receptor antagonists) relative to their optimal doses was computed. Patients were classified into 3 dose categories: low (<50%), medium (≥50% to <90%), and high (≥90%). Dose and dose group were included as a time-dependent covariate in Cox regression models, which were used to test whether outcomes differed by dose. Main Outcome Measures: Post hoc secondary analyses of postdischarge 180-day HF readmission or death and 90-day change in quality of life. Results: A total of 515 patients (mean [SD] age, 62.7 [13.4] years; 311 male [60.4%]) assigned high-intensity care were included in this analysis. At 2 weeks, 39 patients (7.6%) achieved low doses, 254 patients (49.3%) achieved medium doses, and 222 patients (43.1%) achieved high doses. Patients with lower blood pressure and more congestion were less likely to be uptitrated to optimal GDMT doses at week 2. As a continuous time-dependent covariate, an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-day HF readmission or all-cause death (primary end point: adjusted hazard ratio [aHR], 0.89; 95% CI, 0.81-0.98; P = .01) and a decrease in 180-day all-cause mortality (aHR, 0.84; 95% CI, 0.73-0.95; P = .007). Quality of life at 90 days, measured by the EQ-5D visual analog scale, improved more in patients treated with higher doses of GDMT (mean difference, 0.10; 95% CI, -4.88 to 5.07 and 3.13; 95% CI, -1.98 to 8.24 points in the medium- and high-dose groups relative to the low-dose group, respectively; P = .07). Adverse events to day 90 occurred less frequently in participants with HIC who were prescribed higher GDMT doses at week 2. Conclusions and Relevance: Results of this post hoc analysis of the STRONG-HF randomized clinical trial show that, among patients randomly assigned to high-intensity care, achieving higher doses of HF GDMT 2 weeks after discharge was feasible and safe in most patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03412201.

A 10% blood pressure drop from baseline during mechanical thrombectomy for stroke is strongly associated with worse neurological outcomes.

BACKGROUND: Mechanical thrombectomy (MT) for acute ischemic stroke can be performed under local anesthesia, with or without conscious sedation (CS), or under general anesthesia (GA). The hemodynamic consequence of anesthetic drugs may explain why GA may be associated with worse outcomes. We evaluated the association between hypotension duration during MT and the 90 day functional outcome under both anesthetic regimens. METHODS: Patients were included in this retrospective study if they had an ischemic stroke treated by MT under GA or CS. The main exposure variable was the time below 90% of the reference value of arterial pressure measured before MT. The primary outcome was poor functional outcome defined as a 90 day modified Rankin Score ≥3. RESULTS: 371 patients were included in the study. GA was performed in 42%. A linear association between the duration of arterial hypotension and outcome was observed. The odds ratio for poor functional outcome of 10 min under 90% of the baseline mean arterial pressure was 1.13 (95% CI 1.06 to 1.21) without adjustment and 1.11 (95% CI 1.02 to 1.21) after adjustment for confounding factors. The functional outcome was poorer for patients treated under GA compared with CS, but the association with the depth of hypotension remained similar under both conditions. CONCLUSION: In this study, we observed a linear association between the duration of hypotension during MT and the functional outcome at 90 days. An aggressive and personalized strategy for the treatment of hypotension should be considered. Further trials should be conducted to address this question.

Auriculotherapy in the prevention of postoperative urinary retention in patients with thoracotomy and thoracic epidural analgesia: A randomized, double-blinded trial.

BACKGROUND: Thoracic epidural analgesia is associated with a high rate of postoperative urine retention (POUR). Auriculotherapy can reduce visceral dysfunction and can be helpful in anesthesiology and pain control. The aim of this study was to test the efficacy of preoperative auriculotherapy to decrease the occurrence of POUR. METHODS: This single-center, double-blinded, 2-arm randomized study was performed between January 2015 and May 2016 in a tertiary care university hospital. Male patients scheduled for an elective lung surgical procedure under combined general anesthesia and thoracic epidural analgesia were included. Auriculotherapy (A group) was performed once the patient was under general anesthesia with 5 semi-permanent needles inserted in both ears at the "Shen Men" "bladder", "pelvic parasympathetic", "anterior hypothalamus", and "frontal lobe" points. Five small round patches of adhesive pads were positioned bilaterally at the same points in the control group (C group). The main outcome measure was the requirement for bladder catheterization during the day and the first night following surgery. RESULTS: Fifty-three patients were randomized and 25 analyzed in each group. Requirement for bladder catheterization was different between groups: 24 C group patients (96%) and 18 A group patients (72%) (P = .049, Fisher exact test; Odds Ratio = 0.11 [0.01-0.95]. The number of patients needed to treat with auriculotherapy to avoid 1 case of bladder catheterization was 4. No adverse effect was observed due to auriculotherapy. CONCLUSION: This study demonstrates that auriculotherapy is a safe and useful technique reducing POUR in thoracotomy patients benefiting from thoracic epidural analgesia. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02290054 (November 13, 2014).

Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study.

BACKGROUND: The introduction of cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improved the prognosis of selected patients with peritoneal mesothelioma (PM). OBJECTIVE: The objective of our study was to evaluate whether different HIPEC agents were associated with different outcomes in patients with PM. METHODS: From the RENAPE database, we selected all patients with histology-proven PM who underwent CRS + HIPEC from 1989 to 2014. Inclusion criteria were age ≤ 80 years, performance status ≤ 2, and no extraperitoneal metastases. RESULTS: Overall, 249 patients underwent CRS + HIPEC for PM. The HIPEC regimen included five chemotherapeutic agents (CAs), consisting of cisplatin, doxorubicin, mitomycin-C, oxaliplatin, and irinotecan. When considering all CAs (alone or in combination), there was no significant statistical difference in regard to postoperative overall survival (OS). However, OS was better when using two CAs (group 2 drugs) versus one CA (group 1 drug) (p = 0.03). The different CA regimens were equally distributed between the two groups. This association between OS and HIPEC agent, as well as a trend for better progression-free survival, were both observed in the two-drug group versus the one-drug group (p = 0.009) for patients undergoing complete cytoreductive surgery (CC-0) with an epithelioid subtype. CONCLUSIONS: This large study seems to show improved OS when combined CAs, especially with platinum-based regimens, are used for HIPEC in patients with PM, but needs to be confirmed by a randomized controlled trial.

Prediction of Resectability in Pseudomyxoma Peritonei with a New CT Score.

BACKGROUND: Curative treatment of pseudomyxoma peritonei (PMP) is complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). OBJECTIVE: The aim of this study was to build and evaluate a preoperative imaging score to predict resectability. PATIENTS AND METHODS: Between 2007 and 2014, all PMP patients in two tertiary reference centers who underwent laparotomy with intent to undergo CRS and HIPEC were included in this study retrospectively. Thickness of tumor burden was measured on preoperative multidetector-row computed tomography (MDCT) by two radiologists blinded to surgical results in five predetermined areas. Patients were divided into two cohorts with the same resectability rate (building and validation). The performances of the scores were assessed using receiver operating characteristic (ROC) curve analyses. RESULTS: Overall, 126 patients were included, with compete CRS being achieved in 91/126 patients (72.2%). Two cohorts of 63 patients matched by age, sex, burden of disease, resectability rate, and pathological grade were constituted. The MDCT score was the sum of the five measures, and was higher in unresectable disease [median 46.2 mm (range 27.9-74.6) vs. 0.0 mm (range 0.0-14.0), p < 0.001]. Area under the ROC curve was 0.863 (range 0.727-0.968) and 0.801 (range 0.676-0.914) in the building and validation cohorts, respectively. A threshold of 28 mm yielded a sensitivity, specificity, positive predictive and negative predictive value of 94, 81, 81 and 94% in the building cohort, and 80, 68, 59 and 85% in the validation cohort, respectively. Using our score, overall and disease-free survival were increased in the group classified as resectable. CONCLUSION: A simple preoperative MDCT score measuring tumor burden in the perihepatic region is able to predict resectability and survival of PMP patients.

Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin.

BACKGROUND: Patients with stage IV colorectal cancer and peritoneal carcinomatosis are increasingly treated with curative intent and perioperative systemic chemotherapy combined with targeted therapy. The aim of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin. METHODS: From 2004 to 2010, in three referral centers, 182 patients with colorectal carcinomatosis were treated with complete cytoreduction followed by HIPEC after either preoperative systemic chemotherapy alone or in combination with bevacizumab. Because there was no control on treatment allocation, propensity score methods were used to control for this bias. RESULTS: The median time from discontinuation of bevacizumab to HIPEC was 7 weeks (range 6-10 weeks). Major morbidity was greater in the bevacizumab group (34 vs. 19 %, p = 0.020). Nine patients died postoperatively, 5 (6.2 %) in the bevacizumab group (n = 80) and 4 (3.9 %) in the group treated with chemotherapy alone (n = 102) (p = 0.130). The rate of digestive fistulas was greater in the bevacizumab group, although not statistically significant (18 vs. 10 %, p = 0.300). The effect of bevacizumab on major morbidity (including death) was found to be statistically significant (odds ratio 2.28, 95 % confidence interval 1.05-4.95) (p = 0.04). CONCLUSIONS: Administration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for colorectal carcinomatosis is associated with twofold increased morbidity. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.

Impact of diuretic dosing on mortality in acute heart failure using a propensity-matched analysis.

AIMS: Loop diuretics are recommended to treat congestion in heart failure (HF), despite limited quality evidence. High-dose (HD) loop diuretics seem to worsen outcomes in chronic HF, though; data for acute HF are scarce, with equivocal results. METHODS AND RESULTS: The ALARM-HF study recorded in-hospital HF therapy in 4953 patients from nine countries. A post-hoc analysis was performed to determine if there was an interaction between intravenous (iv) bolus diuretic dosing and outcomes. Patients were classified as receiving high- or low-dose iv furosemide if their total initial 24 h dose was above (HD) or below [low dose (LD)] 1 mg/kg. Propensity scoring, matching an extensive list of variables, was performed. High-dose and LD patients were matched by propensity scores and outcomes determined. We identified 2460 LD and 848 HD patients, with overall in-hospital mortality of 9 and 13% (P= 0.002), respectively. After propensity matching, there were 506 patients in each subgroup, with the matched LD and HD cohorts having similar mortality (13 vs. 15%; P= 0.4). We further investigated in which subgroups of patients HD diuretics influenced mortality. Before matching, HD diuretics were associated with a greater risk of in-hospital death in some subgroups, including patients aged >80 years, those with an acute coronary syndrome, or with a left ventricular ejection fraction <40%. However, after propensity score matching, no association was found between diuretic dosing and death in any of the studied subgroups. CONCLUSIONS: In the initial management of acute HF, HD iv diuretics, per se, do not influence short-term mortality.