A nationwide prospective registry of bortezomib-based therapy in light chain (AL) amyloidosis.

Until recently, no drug was labeled for AL amyloidosis. In 2011, the Italian Medicines Agency started a program to grant access to upfront bortezomib to patients with AL amyloidosis. All subjects were enrolled in a prospective online registry. Response was evaluated after two cycles to assess the possibility of continuing treatment. A total of 764 patients were included until 2019, and 615 were evaluable. Sixteen percent of patents had advanced (stage-IIIb) heart involvement, and 27% had severe or end-stage renal failure. Bortezomib delivery was possible in stage-IIIb patients at a reduced dose. Bortezomib discontinuation was associated with increasing age, advanced heart involvement and bi-weekly administration. Fifty-nine percent of subjects attained a hematologic response and 14% a cardiac response. Bortezomib-based therapy tends to be discontinued early in elderly patients and in advanced disease. Nevertheless, early response to therapy is possible in this challenging population.

Incidence and Predictors of Postoperative Need for High-Dose Inotropic Support in Patients Undergoing Cardiac Surgery for Infective Endocarditis.

OBJECTIVE: Patients with infective endocarditis undergoing cardiac surgery are a high-risk population. Few data on incidence and predictors of need for high-dose inotropic support in this setting are currently available. DESIGN: Retrospective study. SETTING: Tertiary-care hospital. PARTICIPANTS: Ninety consecutive patients undergoing cardiac surgery for infective endocarditis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline, intraoperative and outcome data were collected. Stepwise multiple logistic regression analysis was performed to identify preoperative predictors of postoperative hemodynamic support. High-dose postoperative inotropic support was defined as inotropic score >10 (calculated as dobutamine dose (in µg/kg/min) + dopamine dose (in µg/kg/min) + (epinephrine dose [in µg/kg/min] × 100) + (norepinephrine dose [in µg/kg/min] × 100) + (milrinone dose [in µg/kg/min] × 10) + (vasopressin dose [in U/kg/min] × 10 000) + (levosimendan dose [in µg/kg/min] × 50) or need for mechanical circulatory support at intensive care unit admission. Postoperative high-dose inotropic or mechanical circulatory support was required in 57 cases (61%). Stepwise multiple logistic regression identified 5 variables independently associated with need for postoperative circulatory support: male sex (odds ratio [OR] = 10.9), surgery duration (OR for every minute increase = 1.01), impairment of kidney function (eGFR <60 mL/min/m2 - OR = 19), preoperative new-onset heart failure (defined by clinical, imaging and laboratory parameters - OR = 5.30), and low preoperative platelet count (for every 1×103/µl increase - OR = 0.99). CONCLUSIONS: Patients undergoing cardiac surgery for infective endocarditis are at high risk for postoperative hemodynamic instability. Preoperative organ failure is an important determinant for postoperative hemodynamic instability.

Second cross-clamping after mitral valve repair for degenerative disease in contemporary practice.

OBJECTIVES: Scanty data are available on 'second cross-clamping' following mitral valve repair in contemporary practice. The aim of this study was to evaluate the incidence, causes and outcomes of this event in patients referred for mitral repair for severe degenerative mitral regurgitation (MR). METHODS: The study population included 2318 patients with severe degenerative MR referred for mitral repair. A second cross-clamping was performed in 94 (4%) patients. Causes of the second cross-clamping, revising repair procedures, immediate echocardiographic outcomes and postoperative course were assessed and compared with the 'single cross-clamping cases' (2224 patients used as control). Clinical and echocardiographic follow-up information was available for 91 of the 94 second cross-clamping patients (97% complete) (median time 6 years, interquartile range 3-11). RESULTS: The most frequent causes of the second cross-clamping were residual MR >1+/4+ and systolic anterior motion. A residual prolapse was identified in 41 (43.5%) patients, systolic anterior motion in 22 (23.5%), untreated clefts in 14 (15%) and other mechanisms in 17 (18%). Second cardiopulmonary bypass and aortic cross-clamping times were 36 (range 28-50) and 23 (range 17-34) min, respectively. Hospital mortality was 0% in the second cross-clamping and 0.3% in the control group (P = 0.2). Postoperative complications and length of hospital stay were similar. At discharge, residual MR ≥2+/4+ was 2.1% in the second cross-clamping and 2.7% in the control group (P = 0.99). In the second cross-clamping, at 12 years, the cumulative incidence function of reoperation, recurrent MR ≥3+ and MR ≥2+ with death as competing risk were 5.7 ± 2.5% (95% confidence interval 2-12), 10.3 ± 4.3% (95% confidence interval 3.8-20) and 17 ± 5.2% (95% confidence interval 8-29), respectively. CONCLUSIONS: In a large volume centre for mitral repair, a second cross-clamping is still performed in 3-5% of the patients. Because suboptimal immediate results are associated with impaired late outcomes of mitral reconstruction, a low threshold for a second cross-clamping seems to be justified. If the second repair is carried out with a relatively shorter additional cross-clamping time, mortality and morbidity are not increased and immediate and long-term results are very satisfactory.

Nonsurgical Strategies to Reduce Mortality in Patients Undergoing Cardiac Surgery: An Updated Consensus Process.

OBJECTIVE: A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: More than 400 physicians from 52 countries participated in this web-based consensus conference. INTERVENTIONS: The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide. MEASUREMENTS AND MAIN RESULTS: Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions. CONCLUSIONS: This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field.