Objectives The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro–B-type natriuretic peptide (NT-proBNP) is superior to ...standard of care (SOC) management. Background It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. Methods In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP–guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. Results Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP–guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP–guided care as younger subjects. Compared with SOC, NT-proBNP–guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. Conclusions In patients with HF due to LV systolic dysfunction, NT-proBNP–guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Elderly patients with heart failure (HF) have a worse prognosis than younger patients. We wished to study whether elders benefit from natriuretic peptide-guided HF care in this ...single-center study. Methods and Results A total of 151 patients with HF resulting from left ventricular systolic dysfunction (LVSD) were treated with HF treatment by standard-of-care (SOC) management or guided by N-terminal pro-B type natriuretic peptide (NT-proBNP) values (with a goal to lower NT-proBNP ≤1000 pg/mL) over 10 months. The primary end point for this post-hoc analysis was total cardiovascular events in 2 age categories (<75 and ≥75 years). In those ≥75 years of age (n = 38), NT-proBNP values increased in the SOC arm (2570 to 3523 pg/mL, P = .01), but decreased in the NT-proBNP–guided arm (2664 to 1418 pg/mL, P = .001). Elderly patients treated with SOC management had the highest rate of cardiovascular events, whereas the elderly with NT-proBNP management had the lowest rate of cardiovascular events (1.76 events per patient versus 0.71 events per patient, P = .03); the adjusted logistic odds for cardiovascular events related to NT-proBNP–guided care for elders was 0.24 ( P = .008), whereas in those <75 years (n = 113), the adjusted logistic odds for events following NT-proBNP–guided care was 0.61 ( P = .10). Conclusions Natriuretic peptide–guided HF care was well tolerated and resulted in substantial improvement in cardiovascular event rates in elders (Clinical Trials.Gov #00351390).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective Robotic gynecological surgery is feasible in obese patients, but there remain concerns about the safety of this approach because the positioning required for pelvic surgery can exacerbate ...obesity-related changes in respiratory physiology. The objective of our study was to evaluate pulmonary and all-cause complication rates in obese women undergoing robotic gynecological surgery and to assess variables that may be associated with complications. Study Design A retrospective chart review was performed on obese patients (body mass index of ≥30 kg/m2 ) who underwent robotic gynecological surgery at 2 academic institutions between 2006 and 2012. The primary outcome was pulmonary complications and the secondary outcome was all-cause complications. Univariate and multivariate logistic regression analyses were used to determine the associations between patient baseline variables, operative variables, ventilator parameters, and complications. Results Of 1032 patients, 146 patients (14%) had any complication, whereas only 33 patients (3%) had a pulmonary complication. Median body mass index was 37 kg/m2 . Only age was significantly associated with a higher risk of pulmonary complications ( P = .01). Older age, higher estimated blood loss, and longer case length were associated with a higher rate of all-cause complications ( P = .0001, P < .0001, and P = .004, respectively). No other covariates were strongly associated with complications. Conclusion The vast majority of obese patients can successfully tolerate robotic gynecological surgery and have overall low complications rates and even lower rates of pulmonary complications. The degree of obesity was not predictive of successful robotic surgery and subsequent complications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
AbstractPurposeNRG Oncology's RTOG 0933 demonstrated benefits to memory preservation after hippocampal avoidant whole-brain radiation therapy (HA-WBRT), the avoidance of radiation dose to the ...hippocampus (using intensity modulated radiation planning and delivery techniques) during WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity play a role. White matter injury (WMI) has been implicated in radiation therapy–induced neurocognitive decline. This secondary analysis explored the relationship between pretreatment WMI and memory after HA-WBRT. Methods and MaterialsVolumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pretreatment magnetic resonance image. Correlational analyses were performed examining the relationship between pretreatment WMI and Hopkins Verbal Learning Test-Revised (HVLT-R) outcomes at baseline and 4 months after HA-WBRT. ResultsIn the study, 113 patients received HA-WBRT. Of 113 patients, 33 underwent pretreatment and 4-month posttreatment HVLT testing and pretreatment postcontrast volumetric T1 and axial T2/fluid-attenuated inversion recovery magnetic resonance imaging. Correlation was found between larger volumes of pretreatment WMI and decline in HVLT-R recognition (r = 0.54, P < .05), and a correlational trend was observed between larger volume of pretreatment WMI and decline in HVLT-R delayed recall (r = 0.31, P = .08). Patients with higher pretreatment disease burden experienced a greater magnitude of stability or positive shift in HVLT-R recall and delayed recall after HA-WBRT (r = –0.36 and r = –0.36, P < .05), compared to the magnitude of stability or positive shift in those with lesser disease burden. ConclusionsIn patients receiving HA-WBRT for brain metastases, extent of pretreatment WMI predicts posttreatment memory decline, suggesting a mechanism for radiation therapy–induced neurocognitive toxicity independent of hippocampal stem cell radiosensitivity. Stability or improvement in HVLT after HA-WBRT for patients with higher pretreatment intracranial metastatic burden supports the importance of WBRT-induced intracranial control on neurocognition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. ...Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown. Methods One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome. Results Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (−10.0 vs −5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death ( P = .001). Conclusions We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.gov NCT00351390 ).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian ...racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and ...device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Combined liver-lung transplantation is an uncommon, although vital, procedure for patients with simultaneous end-stage lung and liver disease. The utility of lung-liver transplant has been questioned ...because of initial poor survival outcomes, particularly when compared with liver-alone transplant recipients.
A single-center, retrospective review of the medical records of 19 adult lung-liver transplant recipients was conducted, comparing early recipients (2009-2014) with a recent cohort (2015-2021). Patients were also compared with the center's single lung or liver transplant recipients.
Recent lung-liver recipients were older (
= 0.004), had a higher body mass index (
= 0.03), and were less likely to have ascites (
= 0.02), reflecting changes in the etiologies of lung and liver disease. Liver cold ischemia time was longer in the modern cohort (
= 0.004), and patients had a longer posttransplant length of hospitalization (
= 0.048). Overall survival was not statistically different between the 2 eras studied (
= 0.61), although 1-y survival was higher in the more recent group (90.9% versus 62.5%). Overall survival after lung-liver transplant was equivalent to lung-alone recipients and was significantly lower than liver-alone recipients (5-y survival: 52%, 51%, and 75%, respectively). Lung-liver recipient mortality was primarily driven by deaths within 6 mo of transplant due to infection and sepsis. Graft failure was not significantly different (liver:
= 0.06; lung:
= 0.74).
The severity of illness in lung-liver recipients combined with the infrequency of the procedure supports its continued use. However, particular attention should be paid to patient selection, immunosuppression, and prophylaxis against infection to ensure proper utilization of scarce donor organs.
Background Soluble ST2 (sST2), an interleukin (IL)-1 receptor family member, has a role in immunologic tolerance and has also emerged as a biomarker of cardiac stretch and remodeling. The sST2 role ...in heart transplantation is still unknown. Methods From the heart transplantation population at our institution (n = 74), we selected a subset of 26 patients who had an acute rejection episode in the first year after transplantation (35%; 52 ± 14 years; 76% men). Endomyocardial biopsy (EMB) results obtained at the time of the first rejection episode represented the rejection cohort (n = 26). Each patient served as a control to himself or herself, with EMB without rejection obtained before and after the rejection episode (n = 52). All laboratory measurements and blood samples were obtained at the time of EMB. Results sST2 concentrations rose significantly in the context of acute rejection (130 60 to 238 versus 51 ng/mL 28 to 80; p = 0.002). Tertile analyses of sST2 concentrations revealed a graded association with rejection (p = 0.002) and repeated measurement analyses showed that sST2 concentrations were significantly modulated by the presence of rejection ( p = 0.001). In receiver operator characteristic (ROC) analysis, sST2 had an area under the curve (AUC) of 0.72; the optimal cutoff point was 68 ng/mL (positive predictive value of 53%, negative predictive value of 83%), which predicted acute cellular rejection (odds ratio OR 4.9; 95% confidence interval CI, 1.7 to 14.5; p = 0.004). The addition of sST2 values to those for the N-terminal pro B-type natriuretic peptide (NT-proBNP) resulted in a significant improvement on the integrated discrimination index (IDI) for rejection (relative improvement of 24%; p = 0.021). Conclusions sST2 concentrations are modulated by the presence of acute rejection and provide complementary predictive ability to NT-proBNP for the biochemical identification of rejection.
Cardiac resynchronization therapy (CRT) nonresponders have poor outcomes. The significance of progressive ventricular dysfunction among nonresponders remains unclear.
We sought to define predictors ...of and clinical outcomes associated with progressive ventricular dysfunction despite CRT.
We conducted an analysis of 328 patients undergoing CRT with defibrillator for standard indications. On the basis of 6-month echocardiograms, we classified patients as responders (those with a ≥5% increase in ejection fraction) and progressors (those with a ≥5% decrease in ejection fraction), and all others were defined as nonprogressors. Coprimary end points were 3-year (1) heart failure, left ventricular assist device (LVAD), transplantation, or death and (2) ventricular tachycardia (VT) or ventricular fibrillation (VF).
Multivariable predictors of progressive ventricular dysfunction were aldosterone antagonist use (hazard ratio HR 0.23; P = .008), prior valve surgery (HR 3.3; P = .005), and QRS duration (HR 0.98; P = .02). More favorable changes in ventricular function were associated with lower incidences of heart failure, LVAD, transplantation, or death (70% vs 54% vs 33%; P < .0001) and VT or VF (66% vs 38% vs 28%; P = .001) for progressors, nonprogressors, and responders, respectively. After multivariable adjustment, progressors remained at increased risk of heart failure, LVAD, transplantation, or death (HR 2.14; P = .0029) and VT or VF (HR 2.03; P = .046) as compared with nonprogressors. Responders were at decreased risk of heart failure, LVAD, transplantation, or death (HR 0.44; P < .0001) and VT or VF (0.51; P = .015) as compared with nonprogressors.
Patients with progressive deterioration in ventricular function despite CRT represent a high-risk group of nonresponders at increased risk of worsened clinical outcomes.
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