Lower 1-year Mortality Research Articles

Association of Renin-Angiotensin Inhibitor Treatment With Mortality and Heart Failure Readmission in Patients With Transcatheter Aortic Valve Replacement

Data are lacking on the effect of a renin-angiotensin system (RAS) inhibitor prescribed after transcatheter aortic valve replacement (TAVR). Treatment with a RAS inhibitor may reverse left ventricular remodeling and improve function. To investigate the association of prescription of a RAS inhibitor and outcomes after TAVR. Retrospective cohort study of TAVR procedures performed in the United States (using the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry) between July 2014 and January 2016 that were linked to Medicare claims data (final date of follow-up: March 31, 2017). To account for differences in demographics, echocardiographic findings, and in-hospital complications, 1:1 propensity matching was performed. Initial hospital discharge prescription of a RAS inhibitor after TAVR. Primary outcomes were all-cause death and readmission due to heart failure at 1 year after discharge, which were considered separately. The secondary outcome was health status assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ; score range: 0-100, with a higher score indicating less symptom burden and better quality of life; a small effect size was defined as 5 points) at 1 year. Among 21 312 patients who underwent TAVR at 417 US sites, 8468 patients (39.7%) were prescribed a RAS inhibitor at hospital discharge. After propensity matching, 15 896 patients were included (mean [SD] age, 82.4 [6.8] years; 48.1% were women; mean [SD] left ventricular ejection fraction [LVEF], 51.9% [11.5%]). Patients with a prescription for a RAS inhibitor vs those with no prescription had lower mortality rates at 1 year (12.5% vs 14.9%, respectively; absolute risk difference [ARD], -2.4% [95% CI, -3.5% to -1.4%]; hazard ratio [HR], 0.82 [95% CI, 0.76 to 0.90]) and lower heart failure readmission rates at 1 year (12.0% vs 13.8%; ARD, -1.8% [95% CI, -2.8% to -0.7%]; HR, 0.86 [95% CI, 0.79 to 0.95]). When stratified by LVEF, having a prescription for a RAS inhibitor vs no prescription was associated with lower 1-year mortality among patients with preserved LVEF (11.1% vs 13.9%, respectively; ARD, -2.81% [95% CI, -3.95% to -1.67%]; HR, 0.78 [95% CI, 0.71 to 0.86]), but not among those with reduced LVEF (18.8% vs 19.5%; ARD, -0.68% [95% CI, -3.52% to 2.20%]; HR, 0.95 [95% CI, 0.81 to 1.12]) (P = .04 for interaction). Of 15 896 matched patients, 4837 (30.4%) were included in the KCCQ score analysis and improvements at 1 year were greater in patients with a prescription for a RAS inhibitor vs those with no prescription (median, 33.3 [interquartile range, 14.2 to 51.0] vs 31.3 [interquartile range, 13.5 to 51.1], respectively; difference in improvement, 2.10 [95% CI, 0.10 to 4.06]; P < .001), but the effect size was not clinically meaningful. Among patients who underwent TAVR, receiving a prescription for a RAS inhibitor at hospital discharge compared with no prescription was significantly associated with a lower risk of mortality and heart failure readmission. However, due to potential selection bias, this finding requires further investigation in randomized trials.

Effect of PET/CT on the Management and Outcomes of Participants with Hodgkin and Aggressive Non-Hodgkin Lymphoma: A Multicenter Registry.

Purpose To determine the relationship of PET/CT staging to the management and outcomes of participants with apparent limited-stage (LS) Hodgkin lymphoma (HL) or aggressive non-HL (ANHL) treated with curative intent. Materials and Methods This prospective multicenter registry included 850 participants (467 men and 383 women; median age, 54.1 years) from nine centers who had LS HL or ANHL on the basis of clinical data and CT, or with equivocal CT for advanced stage, who were considered for curative-intent first-line therapy. Participants were recruited between May 1, 2013, and December 31, 2015. Pre-PET/CT treatment plan was compared with treatment provided. Survival and second-line therapy initiation were compared with an historical control pool staged by using CT alone. Administrative data sources were used to control for baseline characteristics. Outcomes were assessed by using adjusted Cox proportional hazards regression and propensity score matching. Results PET/CT helped to upstage 150 of 850 participants (17.6%). There was a change in planned therapy in 224 of 580 (38.6%) of participants after PET/CT. There was a lower 1-year mortality for participants with ANHL in the PET/CT versus CT cohort (hazard ratio, 0.63; 95% confidence interval: 0.40, 1.0; P < .05) and for those with LS at PET/CT compared with those with LS at CT (hazard ratio, 0.40; 95% confidence interval: 0.21, 0.74; P = .004). For participants with HL, no 1-year outcome difference was found (P = .16). Conclusion PET/CT helped to upstage approximately 18% of participants and planned management was frequently altered. Participants with aggressive non-Hodgkin lymphoma whose first-line therapy was guided by PET/CT had significantly better survival compared with participants whose treatment was guided by CT. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Scott in this issue.

Adjuvant Doxycycline to Enhance Anti-Amyloid Effects: Results from the DUAL (Doxycycline to Upgrade response in AL amyloidosis) Study

Background: Light chain (AL) amyloidosis is associated with misfolded, insoluble fibril deposits in vital organs such as the heart, kidneys, liver, and nerves, derived from immunoglobulin light chains made by clonal plasma cells. Plasma cell-directed, standard-of-care chemotherapy has no effect on pre-formed fibrils. Hematologic response is thus insufficient for organ amyloid responses and organ improvement can lag hematologic response by months to years. Fibril-directed therapies are critical to improve early mortality of AL. Doxycycline has been reported to produce fibril disruption, reduce AL deposits and control light chain toxicity. It has been studied in localized AL amyloidosis and other amyloid subtypes. We conducted a phase 2 trial of doxycycline for use in conjunction with chemotherapy in AL. Herein, we report the outcomes of systemic AL patients treated on this study.Patients and Methods: This was an open label, single center, phase 2 pilot trial listed under clinicaltrials.gov (NCT02207556). The study was opened between 12/2014 - 06/2017. The last patient completed end-of-study assessment in 07/2018. Based on predominant symptoms and organ involvement, each patient was labeled to have 1 target amyloid organ involved. Patients were treated with oral doxycycline 100 mg twice daily in conjunction with chemotherapy per physician discretion. Patients were staged using the 2012 staging system. Hematologic and organ responses were categorized based on the consensus guidelines for conduct and reporting of clinical trials in AL amyloidosis published in 2012 for cardiac, renal and hepatic organ involvement and by radiologic measures for soft tissue involvement. The objectives were to study early mortality at 1, 3, 6, and 12 months after enrollment, target amyloid organ response rates at 6 and 12 months, and quality of life (QoL) using the PROMIS Global Health Index at 3-monthly intervals during the study.Results: Of 31 patients enrolled on this study, 25 had systemic AL (6 patients with localized AL syndromes will be described separately). The median age at diagnosis was 61.3 years (range 38.3-77.3), 64% were male, 2012 stage was I in 3 (12%), II in 9 (36%), III in 6 (24%) and IV in 7 (28%). The amyloid clone was lambda in 17 (68%). The median baseline values with range were: hemoglobin 12.3 (9.7-16.5) g/dL, albumin 3.7 (1.1-4.8) g/dL, creatinine 1.07 (0.6-2.42) mg/dL, 24-hour urine protein 0.97 (0.15-16.7) g/day and alkaline phosphatase 77 (42-597) IU/L. The median difference in involved and uninvolved free light chains was 258.6 (26-978.4) mg/L, NT-proBNP was 2564 (65-18333) pg/mL and troponin T was 0.017 (<0.011-0.342) ng/mL. Among AL organ involvement, 16% had 1, 24% had 2, 16% had 3, and 44% had >3 organs involved with amyloid, with 60% cardiac, 72% renal, 24% hepatic, 36% soft tissue, 28% gastrointestinal, 20% autonomic nervous system, and 8% peripheral nerve AL involvement. The median follow-up was 21.4 (12.2-40.3) months.All patients received concurrent CyBorD chemotherapy. Early mortality was 0 at 1 month, 2 (8%) at 3 months, 3 (12%) at 6 months and 5 (20%) at 1 year. Target organ involvement and responses at 6 and 12 months are shown in the table. In an intent-to-treat analysis of organ responses, at 6 months 24% had response, 32% had stable disease and 44% had progression (including 3 deaths prior to 6 months). At 12 months, 36% had target organ response, 32% had stable disease and 36% had progression (including 5 deaths). QoL showed improvement in both physical and mental domains at the end of treatment (figure). Overall hematologic response among survivors was 100% at 1-year including 40% complete, 45% very good, and 15% partial responses. The most common adverse event was skin rash and photosensitivity. One patient with end-stage heart failure and multiple hospitalizations, developed Clostridium difficile diarrhea while hospitalized, during the study period. Fifteen patients (60%) underwent melphalan-based autologous stem cell transplantation- 14 within 1 year after diagnosis, and in 1 delayed until relapsed disease 2 years after diagnosis. The 100-day mortality among transplanted patients was 0.Conclusions: In newly diagnosed systemic AL amyloidosis, doxycycline was safe with concurrent chemotherapy. The low 1-year early mortality of 20% and autologous stem cell transplant rate of 60% compares favorably to prior reports. These findings warrant a randomized, multicenter study. [Display omitted] DisclosuresD'Souza:Prothena: Consultancy, Research Funding; Merck: Research Funding; Takeda: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Dhakal:Celgene: Consultancy, Honoraria; Takeda: Honoraria, Research Funding; Amgen: Honoraria. Hari:Janssen: Honoraria; Amgen Inc.: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding.

Diabetic retinopathy grade as a predictive marker of severity of cardiovascular disease and mortality: DIVERSE Study Group

Patients with diabetic retinopathy (DR) are more likely to have subclinical cardiovascular disease. Objective of this study was to assess the prevalence and association of DR grades along with comorbidities in patients with established cardiovascular disease (CVD); association of DR grades beyond ocular morbidity, i.e., long-term outcomes among established CVD; influence of DR grades on prognosis in patients undergoing coronary revascularization. This was a single center, retrospective, data analysis of T2DM patients with established CVD. Goodness of fit was analyzed using Pearson’s chi-square test. DR was observed in 64% (n = 2560) of patients (non-proliferative diabetic retinopathy [NPDR] 37%; proliferative diabetic retinopathy [PDR] 27%). DR and CVD were strongly associated; highest association was observed for congestive heart failure (CHF) (n = 1325), followed by myocardial infarction (MI) (n = 795), unstable angina (UA) (n = 275), and cardiomyopathy (n = 165) (p < 0.00001). Patients with NPDR have greater risk of CHF, MI, UA, and cardiomyopathy vs. PDR [HR 1.32, 1.44, 1.2, and 1.75 respectively]. Five-year all-cause mortality was significantly higher in patients with DR (94.2%; n = 766) vs. that in patients with non-DR (5.78%; n = 47) (p < 0.00001). NPDR patients undergoing CABG (n = 765) had lower 5-year mortality than those underwent PTCA (n = 615) (8.36% vs. 25.85%, p < 0.00001).Three times lower 5-year mortality rate was noted in patients with PDR undergoing CABG vs. that in patients undergoing PTCA (n = 265) (25.3 vs. 72.2%, p < 0.00001). DR was strongly associated with CVD with highest association with CHF, followed by MI, UA, and cardiomyopathy. Cardiovascular events, cerebrovascular events, mortality, and all-cause mortality were higher in patients with DR. Higher risk of mortality was noted in NPDR patients who underwent PTCA than in NPDR patients who underwent CABG.

Association of Medicaid Expansion With 1-Year Mortality Among Patients With End-Stage Renal Disease

The Affordable Care Act Medicaid expansion may be associated with reduced mortality, but evidence to date is limited. Patients with end-stage renal disease (ESRD) are a high-risk group that may be particularly affected by Medicaid expansion. To examine the association of Medicaid expansion with 1-year mortality among nonelderly patients with ESRD initiating dialysis. Difference-in-differences analysis of nonelderly patients initiating dialysis in Medicaid expansion and nonexpansion states from January 2011 to March 2017. Living in a Medicaid expansion state. The primary outcome was 1-year mortality. Secondary outcomes were insurance, predialysis nephrology care, and type of vascular access for hemodialysis. A total of 142 724 patients in expansion states (mean age, 50.2 years; 40.2% women) and 93 522 patients in nonexpansion states (mean age, 49.7; 42.4% women) were included. In Medicaid expansion states, 1-year mortality following dialysis initiation declined from 6.9% in the preexpansion period to 6.1% after expansion (change, -0.8 percentage points; 95% CI, -1.1 to -0.5). In nonexpansion states, mortality rates were 7.0% before expansion and 6.8% after expansion (change, -0.2 percentage points; 95% CI, -0.5 to 0.2), yielding an adjusted absolute reduction in mortality in expansion states of -0.6 percentage points (95% CI, -1.0 to -0.2). Mortality reductions were largest for black patients (-1.4 percentage points; 95% CI, -2.2, -0.7; P=.04 for interaction) and patients aged 19 to 44 years (-1.1 percentage points; 95% CI, -2.1 to -0.3; P=.01 for interaction). Expansion was associated with a 10.5-percentage-point (95% CI, 7.7-13.2) increase in Medicaid coverage at dialysis initiation, a -4.2-percentage-point (95% CI, -6.0 to -2.3) decrease in being uninsured, and a 2.3-percentage-point (95% CI, 0.6-4.1) increase in the presence of an arteriovenous fistula or graft. Changes in predialysis nephrology care were not significant. Among patients with ESRD initiating dialysis, living in a state that expanded Medicaid under the Affordable Care Act was associated with lower 1-year mortality. If this association is causal, further research is needed to understand what factors may have contributed to this finding.

Short- and Long-Term Prognostic Relevance of Cardiogenic Shock in Takotsubo Syndrome: Results From the RETAKO Registry

ObjectivesThis study sought to describe the incidence, determinants, and prognostic impact of cardiogenic shock (CS) in takotsubo syndrome (TTS). BackgroundTTS can be associated with severe hemodynamic instability. The prognostic implication of CS has not been well characterized in large studies of TTS. MethodsWe analyzed patients with a definitive TTS diagnosis (modified Mayo criteria) who were recruited for the National RETAKO (Registry on Takotsubo Syndrome) trial from 2003 to 2016. Cox and competing risk regression models were used to identify factors associated with mortality and recurrences. ResultsA total of 711 patients were included, 81 (11.4%) of whom developed CS. Male sex, QTc interval prolongation, lower left ventricular ejection fraction at admission, physical triggers, and presence of “a significant” left intraventricular pressure gradient, were associated with CS (C index = 0.85). In-hospital complication rates, including mortality, were significantly higher in patients with CS. Over a median follow-up of 284 days (interquartile range: 94 to 929 days), CS was the strongest independent predictor of long-term, all-cause mortality (hazard ratio [HR]: 5.38; 95% confidence interval [CI]: 2.60 to 8.38); cardiovascular (CV) death (sub-HR: 4.29; 95% CI: 2.40 to 21.2), and non-CV death (sub-HR: 3.34; 95% CI: 1.70 to 6.53), whereas no significant difference in the recurrence rate was observed between groups (sub-HR: 0.76; 95% CI: 0.10 to 5.95). Among patients with CS, those who received beta-blockers at hospital discharge experienced lower 1-year mortality compared with those who did not receive a beta-blocker (HR: 0.52; 95% CI: 0.44 to 0.79; pinteraction = 0.043). ConclusionsCS is not uncommon and is associated with worse short- and long-term prognosis in TTS. CS complicating TTS may constitute a marker of underlying disease severity and could identify a masked heart failure phenotype with increased vulnerability to catecholamine-mediated myocardial stunning.

Transcatheter Aortic Valve Replacement With a Repositionable Self-Expanding Prosthesis: The PORTICO-I Trial 1-Year Outcomes

BackgroundThe new self-expanding, repositionable transcatheter heart valve (THV) system was designed for treatment of severe, symptomatic aortic stenosis in patients with high surgical risk. ObjectivesThe purpose of this study was to report 1-year outcomes of transcatheter aortic valve replacement with the new THV system. MethodsThis ongoing, international, multicenter study evaluated patients with severe, symptomatic aortic stenosis implanted with the THV via transfemoral access and follow-up at 30 days, 1 year, and annually through 5 years. The primary endpoint is all-cause mortality at 1 year; secondary endpoints include clinical outcomes and echocardiographic measurements, both adjudicated. ResultsA total of 941 patients (82.4 ± 5.9 years; 65.7% female; Society of Thoracic Surgeons Predicted Risk of Operative Mortality score: 5.8%) were enrolled and underwent an implant at 61 sites in Europe, Australia, and Canada. At 1 year, Kaplan-Meier estimates for all-cause mortality, cardiovascular mortality, disabling stroke rates, and myocardial infarction were 12.1%, 6.6%, 2.2%, and 2.5%, respectively. Mean aortic transvalvular gradient and aortic valve area were 8.66 mm Hg and 1.75 cm2, respectively. Paravalvular leakage was moderate or higher in 2.6% of patients with no severe leakage. New pacemaker rates were 18.7% and 21.3% for pacemaker naïve patients at 30 days and 1 year, respectively. Functional class, exercise capacity, and quality of life improved significantly from baseline to 1 year. ConclusionsTranscatheter aortic valve replacement with the new THV in patients who are at increased surgical risk is associated with low 1-year mortality and stroke rates. Favorable hemodynamic results at 1 year are observed with low transvalvular pressure gradient and incidence of significant paravalvular leakage. (5 Year Observation of Patients With PORTICO Valves [PORTICO-I]; NCT01802788)

Association between process performance measures and 1-year mortality among patients with incident heart failure: a Danish nationwide study.

To examine the association between fulfilment of performance measures supported by clinical guidelines recommendations and 1-year mortality among patients with incident heart failure (HF) in Denmark. A nationwide population-based follow-up study based on the Danish Heart Failure Registry. All Danish hospital departments caring for patients with HF. We identified 24308 in- and outpatients diagnosed with HF from 2003 to 2010. Quality of care was defined as receiving the guideline recommended processes of care: use of echocardiography, New York Heart Association classification, treatment with angiotensin-converting-enzyme inhibitors/angiotensin-II-receptor blocker, beta blockers, physical training, and patient education. Main outcome measure is 1-year mortality. We used multiple imputation and multivariable Cox proportional hazard regression to compute hazard ratios (HRs) for 1-year mortality adjusted for potential confounding factors. Within 1 year, 17.1% of the patients died and the adjusted HRs ranged from 0.61 [95% confidence interval (CI) 0.55-0.67] for patient education to 0.99 (95% CI 0.90-1.10) for beta blocker therapy. The association between meeting more performance measures and 1-year mortality appeared to follow a dose-response pattern: using 0-25% of fulfilled measures as reference, patients who fulfilled 76-100% of the performance measures had an adjusted HR of 0.43 (95% CI 0.38-0.48), while the adjusted HR was 0.96 (95% CI 0.86-1.07) for patients who fulfilled between 26% and 50% of the performance measures. Meeting process performance measures, which reflect care in concordance with clinical guideline recommendations, was associated with substantially lower 1-year mortality among patients with incident HF.

Patterns and Outcomes of the Top of the Basilar Artery Syndrome: The Role of the Posterior Communicating Artery

Background: Clinical syndromes secondary to infarcts in the distal basilar artery (BA) area have been described as “top of the basilar” (TOB) syndrome. However, in the era of advanced imaging technology, it has been realized that the clinical and imaging features are quite diverse in patients with distal BA occlusion. The aim of the present study was to investigate the patterns and clinical outcomes of TOB assessed with modern images and categorize TOBs accordingly. Additionally, we examined the possible influence of the posterior communicating artery (PcoA) on the patterns of TOB. Methods: Patients with distal BA occlusion on magnetic resonance angiography were categorized as TOB-A, and those with multiple lesions in the distal BA territory on diffusion-weighted magnetic resonance imaging as TOB-L. Patients with angiographically and lesion distribution-defined TOB were classified as having TOB-A&L; those with angiographically defined TOB as having TOB-A without TOB-L; and those with lesion distribution-defined TOB as having TOB-L without TOB-A. The PcoA was categorized as “textbook-type” (good P1) and “fetal-type” (absent P1). Factors associated with unfavorable short-term outcomes (modified Rankin Scale 5–6 at discharge), and 1-year and long-term mortalities, were assessed. Results: Of 1,466 patients with ischemic stroke in the posterior circulation who were admitted to Asan Medical Center within 24 h of symptom onset, 124 (8.5%) had TOB, including 45 with TOB-A&L, 44 with TOB-A, and 35 with TOB-L. NIHSS scores (21 [9.5–26] vs. 6 [3–11.5] vs. 6 [3–9]; p < 0.01) and rates of motor deficit (75.6 vs. 54.5 vs. 34.4%; p < 0.01), concomitant pontine lesions (17.8 vs. 25.0 vs. 2.9%; p < 0.01), PcoA presence (44.4 vs. 68.2 vs. 25.7%; p < 0.01), and unfavorable short-term outcomes (62.2 vs. 25.0 vs. 14.3%; p < 0.01) differed significantly in the 3 patient groups. Multivariate analysis showed that textbook-type PcoA was independently associated with a lower frequency of unfavorable short-term outcomes (OR 0.15, 95% CI 0.03–0.70). Reperfusion therapy (hazard ratio [HR] 0.25, 95% CI 0.07–0.89) and the presence of textbook-type PcoA (HR 0.20, 95% CI 0.05–0.90) were associated with a lower 1-year mortality rate after stroke. Conclusion: Patterns and clinical outcomes of TOB vary and are affected by the hemodynamic status of the arterial system, such as BA recanalization and the presence of textbook-type PcoA.

Transcatheter Aortic Valve Replacement of Failed Surgically Implanted Bioprostheses: The STS/ACC Registry

BackgroundValve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) has been shown to be feasible, yet the safety and efficacy in relation to native valve (NV) TAVR are not known. ObjectivesThis study sought to evaluate the safety and effectiveness of ViV TAVR for failed surgical aortic valve replacement (SAVR) by comparing it with the benchmark of NV TAVR. MethodsPatients who underwent ViV-TAVR (n = 1,150) were matched 1:2 (on sex, high or extreme risk, hostile chest or porcelain aorta, 5-m-walk time, and Society of Thoracic Surgeons Predicted Risk of Mortality for reoperation) to patients undergoing NV-TAVR (n = 2,259). Baseline characteristics, procedural data, and in-hospital outcomes were obtained from the Transcatheter Valve Therapy Registry. The 30-day and 1-year outcomes were obtained from linked Medicare administrative claims data. ResultsUnadjusted analysis revealed lower 30-day mortality (2.9% vs. 4.8%; p < 0.001), stroke (1.7% vs. 3.0%; p = 0.003), and heart failure hospitalizations (2.4% vs. 4.6%; p < 0.001) in the ViV-TAVR compared with NV-TAVR group. Adjusted analysis revealed lower 30-day mortality (hazard ratio: 0.503; 95% confidence interval: 0.302 to 0.839; p = 0.008), lower 1-year mortality (hazard ratio: 0.653; 95% confidence interval: 0.505 to 0.844; p = 0.001), and hospitalization for heart failure (hazard ratio: 0.685; 95% confidence interval: 0.500 to 0.939; p = 0.019) in the ViV-TAVR group. Patients in the ViV-TAVR group had higher post-TAVR mean gradient (16 vs. 9 mm Hg; p < 0.001), but less moderate or severe aortic regurgitation (3.5% vs. 6.6%; p < 0.001). Post-TAVR gradients were highest in small SAVRs and stenotic SAVRs. ConclusionsComparison with the benchmark NV-TAVR shows ViV-TAVR to be a safe and effective procedure in patients with failed SAVR who are at high risk for repeat surgery.

GENETIC DETERMINANTS ASSOCIATED WITH THE DEVELOPMENT AND PROGNOSIS OF POSTINFARCTION REMODELING AND CHRONIC HEART FAILURE

Background. The study of the genetic phenotypes of CHF and the search for markers associated with the outcome of the disease may contribute to a better understanding of the pathophysiology of CHF and to target the therapeutic effects. Objective. To research the relationship between clinical, instrumental and genetic factors, including polymorphic variants of the genes HSPB7 (rs1739843), FRMD4B (rs6787362), rs10519210 of the locus 15q22 and MADD (rs10838692, rs2290149) with the survival of patients with postinfarction cardiosclerosis and CHF. Design and methods. The study included 506 men aged 55.4 ± 13.5 years with MI transferred more than 3 months ago. The main group consisted of 260 patients with HF-rEF (CHF I-IV FC, with LVEF (Simpson) &lt;40%), reference group – 246 patients without CHF clinic with LVEF (Simpson)&gt; 55%. The control group consisted of 257 healthy donors, comparable in sex and age. Prospective observation was performed by telephone contact. Results. Allele T and TT genotype polymorphic variant rs2290149 of the MADD gene were associated with the development of IHD and postinfaction cardiosclerosis (p1,2 &lt;0,005). The highest occurrence of the T allele of both polymorphic variants rs2290149 and rs10838692 of the MADD gene was observed in patients with HFrEF (p1,2 &lt;0,0001). CC genotype of polymorphisms (rs2290149, rs10838692) of the MADD gene is associated with a protective effect against IHD with postinfaction cardiosclerosis and, possibly, arterial hypertension, occurring in ≥68% of patients and acting as a competing pathological towards coronary artery disease. The CC genotype of the polymorphic variant rs1739843 of the HSPB7 gene was associated with a lower 3-year mortality in patients with IHD, regardless of LVEF and clinical manifestations of CHF (p &lt;0.05). Conclusion. The findings confirm the need for further genetic analysis of a broader population of CHF patients with ischemic etiology.

Comparison of a Novel Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent: 5-Year Outcomes of the Randomized BIOFLOW-II Trial

ObjectivesThe authors aimed to compare long-term data of an ultrathin cobalt-chromium stent with passive silicon carbide coating and an active biodegradable polymer that releases sirolimus (O-SES) (Orsiro, BIOTRONIK, Bülach, Switzerland) with the durable polymer-based Xience Prime everolimus-eluting stent (X-EES) (Abbott Vascular, Santa Clara, California). BackgroundBiodegradable polymer stents have been developed aiming to overcome long-term detrimental effects of durable polymer stents, ultimately leaving a bare-metal stent in the vessel. MethodsThis multicenter, assessor-blinded trial randomized 452 patients with 505 lesions to either O-SES or X-EES in a 2:1 fashion. Endpoints at 5 years were target lesion failure (TLF), its components, and stent thrombosis. ResultsTLF occurred in 10.4% (n = 30) of O-SES patients versus 12.7% (n = 19) of X-EES patients (p = 0.473), overall stent thrombosis occurred in 0.7% (n = 2) versus 2.8% (n = 4) (p = 0.088), and definite stent thrombosis in 0% versus 0.7% (n = 1) (p = 0.341). Post hoc analysis was performed in diabetic patients (n = 128) and vessels ≤2.75 mm (n = 259). In diabetic patients, the O-SES group had numerically more target lesion revascularizations (13.5% vs. 4.5%; p = 0.138), but fewer cardiac deaths (1.3% vs. 6.9%; p = 0.089) and stent thrombosis (0% vs. 6.9%; p = 0.039). In small vessels, the O-SES group had a significantly lower 5-year mortality (3.7% vs. 11.3%; p = 0.022). ConclusionsAt 5 years, the biodegradable polymer O-SES demonstrated low TLF rates comparable to the durable polymer X-EES, confirming its long-term safety and performance. Particularly encouraging is the absence of definite stent thrombosis.

Pre-ESRD Care and Mortality in Incident ESRD Patients With Multiple Myeloma.

The relationship between mortality and pre-ESRD (end-stage renal disease) nephrology care in incident ESRD patients with multiple myeloma (MM) as the primary cause of renal failure has not been examined. Among 439,206 incident US hemodialysis patients with MM as the primary cause of ESRD (June 1, 2005 to May 31, 2009) identified using the US Renal Data System, adjusted odds ratios (OR) for reported pre-ESRD nephrology care for ESRD due to MM (n=4561) versus other causes (n=434,645) were calculated. The association of pre-ESRD nephrology care with subsequent mortality in MM-ESRD patients was examined. MM-ESRD patients were less likely to have any predialysis nephrology care in the year before initiation of dialysis (34.8% vs. 58.5%; OR=0.38; 95% confidence interval [CI], 0.34-0.43) compared with patients with ESRD due to other causes. MM-ESRD patients compared with others were more likely to have catheters on first dialysis (91.8% vs. 75.6%; OR=4.15; 95% CI, 3.54-4.86). Incident MM-ESRD patients receiving predialysis care for ≥6 months had significantly lower 1-year mortality (hazard ratio 0.89; 95% CI, 0.82-0.97 and 0.88; 95% CI, 0.80-0.96, respectively), relative to those without this care. A catheter for dialysis access was associated with a 1.6-fold increase in 1-year mortality in incident MM-ESRD (hazard ratio 1.55; 95% CI, 1.32-1.83). MM-ESRD patients were less likely to have predialysis nephrology care and more likely to use catheters on first dialysis. However, predialysis care is independently associated with lower mortality in MM-ESRD patients. Predialysis care should be prioritized in MM patients approaching ESRD.

Extrahepatic Portal Hypertension and Portal Vein Thrombosis (Review)

Extrahepatic portal vein thrombosis is the second most frequent cause of portal hypertension after liver cirrhosis. Risk factors of the thrombosis are divided into systemic: hereditary and acquired thrombophilia (60–70%); and local: abdominal inflammation, trauma, surgery, etc. (20–40%). Acute thrombosis episode is often olygo- or asymptomatic and remains undiagnosed until the development of portal hypertension and its complications: gastroesophageal variceal bleeding, portal biliopathy, etc. Early onset of anticoagulation is recommended and should be prescribed at least for 3 months. In patients with portal cavernoma a long-term (even lifelong) anticoagulation is directed to prevent recurrence and extension of thrombosis, especially in case of thrombophilia. Portocaval shunting is the most radical way to correct portal hypertension and to deliver a patient from variceal bleedings and other complications of the disease. Hepatic encephalopathy is a rare condition and generally subclinical. Endoscopic band ligation and sclerotherapy are effective in acute variceal bleeding, primary and secondary prophylaxis of bleeding and should be supplied by non-selective β-adrenoblockers administration. Patients with extrahepatic portal vein thrombosis are well tolerated to variceal bleeding episodes and have high rates of survival during long-term follow-up due to normal liver function. Mortality in these patients is low (5-year mortality is less than 10%) and generally is associated with comorbidities rather complications of portal hypertension

Effect of Optimizing Guideline-Directed Medical Therapy Before Discharge on Mortality and Heart Failure Readmission in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction

Guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF). However, the prognostic impact of medication optimization at the time of discharge in patients hospitalized with heart failure (HF) is unclear. We analyzed 534 patients (73 ± 13 years old) with HFrEF. The status of GDMT at the time of discharge (prescription of angiotensin converting enzyme inhibitor [ACE-I]/angiotensin receptor blocker [ARB] and β blocker [BB]) and its association with 1-year all-cause mortality and HF readmission were investigated. Patients were divided into 3 groups: those treated with both ACE-I/ARB and BB (Both group: n = 332, 62%), either ACE-I/ARB or BB (Either group: n = 169, 32%), and neither ACE-I/ARB nor BB (None group: n = 33, 6%), respectively. One-year mortality, but not 1-year HF readmission rate, was significantly different in the 3 groups, in favor of the Either and Both groups. A favorable impact of being on GDMT at the time of discharge on 1-year mortality was retained even after adjustment for covariates (Either group: hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.21 to 0.90, p = 0.025 and Both group: HR 0.29, 95% CI 0.13-0.65, p = 0.002, vs None group). For 1-year HF readmission, no such association was found. In conclusion, optimization of GDMT before the time of discharge was associated with a lower 1-year mortality, but not with HF readmission rate, in patients hospitalized with HFrEF.

Association of Cardiac Rehabilitation With Decreased Hospitalizations and Mortality After Ventricular Assist Device Implantation

ObjectivesThis study characterized cardiac rehabilitation (CR) use in ventricular assist device (VAD) recipients in the United States and the association of CR with 1-year hospitalization and mortality by using the 2013 to 2015 Medicare files. BackgroundExercise-based CR is indicated in patients with heart failure with reduced ejection fraction, but no data exist regarding CR participation after VAD implantation. MethodsThe study included Medicare beneficiaries enrolled for disability or age >65 years. The investigators identified VAD recipients by diagnosis codes and cumulated CR sessions occurring within 1 year after VAD implantation. Multivariable-adjusted Andersen-Gill models were used to evaluate the association of CR with 1-year hospitalization risk, and Cox regression was used to evaluate the association of CR with 1-year mortality. ResultsThere were 1,164 VADs implanted in Medicare beneficiaries in the United States in 2014. CR use was low, with 348 patients (30%) participating in CR programs. The Midwest had the highest proportion of VAD recipients who began CR (38%), whereas the Northeast had the lowest proportion of CR participants (25%). Each 5-year increase in age was associated with attending an additional 1.6 CR sessions (95% confidence interval [CI]: 0.7 to 2.5; p < 0.001). CR participation was associated with a 23% lower 1-year hospitalization risk (95% CI: 11% to 33%; p < 0.001) and a 47% lower 1-year mortality risk (95% CI: 18% to 66%; p < 0.01) after multivariable adjustment. ConclusionsApproximately one-third of VAD recipients attend CR. Although it is not possible to account fully for unmeasured confounding, VAD recipients who participate in CR appear to have lower risks for hospitalization and mortality.

Comparison of Baseline Characteristics and Outcomes in Men Versus Women With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation

Female gender has been linked to increased risk of adverse events after surgical aortic valve replacement; however, the evidence regarding the role of gender differences on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI) is still debated. This retrospective study included 910 consecutive patients with severe, symptomatic aortic stenosis who underwent TAVI in 2 institutions from January 2012 to July 2016. The primary end point was all-cause mortality at 1 year after TAVI in women versus men. Women had a higher incidence of in-hospital vascular complications (7.8% vs 4.1%) and major or life-threatening bleeding (4.0% vs 1.6%) than men. At 1 year, women showed a lower mortality rate than men (7.0% vs 12.7%, adjusted hazard ratio [HR] 0.42, 95% confidence interval [CI] [0.23 to 0.76], p = 0.004). When stratifying by specific subgroups of interest, the survival benefit in women persisted in (1) patients with a Society of Thoracic Surgery risk score ≤ 8 (adjusted HR 0.35, 95% CI [0.14 to 0.88], p = 0.026); (2) patients treated with first-generation devices (adjusted HR 0.46, 95% CI [0.24 to 0.86], p = 0.016); and (3) patients treated with balloon-expandable valves (adjusted HR 0.40, 95% CI [0.19 to 0.86], p = 0.019). In conclusion, in this large patient cohort, women had lower 1-year mortality after TAVI than men, particularly with an STS score ≤ 8, or treated with first-generation and balloon-expandable devices.

An experimental assessment of the impact of drought and fire on western larch injury, mortality and recovery

Climate change is increasing drought and fire activity in many fire-prone regions including the western USA and circumpolar boreal forest. These changes highlight the need for improved understanding of how multiple disturbances impact trees in these regions. Recent studies linking fire behaviour to plant ecophysiology have improved understanding of how fire affects tree function and mortality but have not investigated interactions between drought stress and fire. In this study, Larix occidentalis saplings were subjected to different levels of water stress followed by low-intensity surface fires in a controlled laboratory setting. Post-fire mortality, recovery and growth were monitored for up to 1 year post fire. Generally, increased pre-fire water stress resulted in decreased post-fire stem diameter (up to 5% lower) and height (up to 19% lower) growth. However, severely water-stressed saplings whose foliage had senesced before the fires had lower 1-year mortality (14%) and significantly greater post-fire bud densities than moderately stressed saplings that did not senesce (86% mortality). The mortality patterns suggest that water-stressed western larch saplings exposed to low-intensity wildfires, or prescribed fires conducted as part of forest management activities, may exhibit lower mortality rates if stress-induced foliar senescence has occurred.

Is There a Sex-Related Difference in the Obesity Paradox in Systolic Heart Failure? Sex-Related Difference in the Obesity Paradox.

PurposeObesity is often associated with better clinical outcomes in heart failure (HF). This so-called obesity paradox remains controversial. The aim of present study was to investigate the prognostic value of obesity in patients hospitalized for systolic HF.Materials and MethodsWe performed a pooled analysis of data from two multicenter, observational HF studies. Patients hospitalized for systolic HF were eligible for the present study. We divided the subjects into two groups, a normal body mass index (BMI) group and a high BMI group. Study endpoints included all-cause mortality and any re-hospitalization within 1 year.ResultsWe enrolled 3145 patients (male, 1824; female, 1321). The high BMI group was significantly associated with lower 1-year mortality rate [odds ratio (OR), 0.543; 95% confidence interval (CI), 0.355−0.832] after adjusting for age, hypertension, diabetes, ischemic HF, previous myocardial infarction, serum creatinine level, anemia, and ejection fraction in men. After adjustment for clinical characteristics, high BMI was not significantly associated with 1-year mortality (OR, 0.739; 95% CI, 0.450−1.216) or 1-year re-hospitalization (OR, 0.958; 95% CI, 0.696−1.319) in women.ConclusionIn pooled analysis of data from two Korean HF registries, the high BMI group was independently associated with lower 1-year mortality rate from systolic HF, especially in men.

Effect of Optimal Medical Therapy at Discharge in Patients With Reperfused ST-Segment Elevation Myocardial Infarction on 1-Year Mortality (from the Regional RESCUe Registry)

Several classes of medication improve survival in patients with ST-segment elevation myocardial infarction (STEMI). We sought to assess the frequency and effect of an optimal therapy upon discharge according to current international guidelines on 1-year all-cause mortality in a prospective cohort of reperfused patients with STEMI. Using data from the French Reseau Cardiologie Urgence (RESCUe) Network, we studied all patients with STEMI admitted and discharged alive from hospital between 2009 and 2013. Class I and II level guidelines were used to define the optimal therapy (OT) group. The undertreatment (UT) group comprised patients in whom at least 1 drug with a class I recommendation was missing. Multivariable Cox regression analysis with propensity score for the prescription of OT was used. Of the 5,161 patients discharged alive, 2,991 (58%) had OT. The 1-year overall survival rate was 0.99 in the OT group (95% confidence interval [CI] 0.99 to 1.00) versus 0.90 (95% CI 0.88 to 0.92) in the UT group. Patient characteristics in the UT group were worse than those in the OT group. After multivariable adjustment, the association between the OT group and mortality remained significant, with a hazard ratio of 0.12 (95% CI 0.07 to 0.22; p<0.001). Optimal secondary prevention therapy in patients with STEMI discharged alive from hospital remains independently associated with lower 1-year mortality.