Katrin Gebauer

Peripheral arterial disease and critical limb ischaemia: still poor outcomes and lack of guideline adherence

AIMS Only few and historic studies reported a bad prognosis of peripheral arterial disease (PAD) and critical limb ischaemia (CLI). The contemporary state of treatment and outcomes should be assessed. METHODS AND RESULTS From the largest public health insurance in Germany, all in- and outpatient diagnosis and procedural data were retrospectively obtained from a cohort of 41 882 patients hospitalized due to PAD during 2009-2011, including a follow-up until 2013. Patients were classified in Rutherford categories 1-3 (n = 21 197), 4 (n = 5353), 5 (n = 6916), and 6 (n = 8416). The proportions of patients with classical risk factors such as hypertension, dyslipidaemia, and smoking declined with higher Rutherford categories (each P < 0.001) while diabetes, chronic kidney disease, and chronic heart failure increased (each P < 0.001). Angiographies and revascularizations were performed less often in advanced PAD (each P < 0.001). In-hospital amputations increased continuously from 0.5% in Rutherford 1-3 to 42% in Rutherford 6, as also myocardial infarctions, strokes, and deaths (each P < 0.001). Among 4298 amputated patients with CLI, 37% had not received any angiography or revascularization neither during index hospitalization nor the 24 months before. During follow-up (mean 1144 days), 7825 patients were amputated and 10 880 died. Kaplan-Meier models projected 4-year mortality risks of 18.9, 37.7, 52.2, and 63.5% in Rutherford 1-3, 4, 5, and 6, and for amputation of 4.6, 12.1, 35.3, and 67.3%, respectively. In multivariable Cox regression models, PAD categories were significant predictors of death, amputation, myocardial infarction, and stroke (each P < 0.001). Length of in-hospital stay (5.8 ± 6.7 days, 10.7 ± 11.1days, 15.2 ± 13.8 days and 22.1 ± 20.3 days; P < 0.001) and mean case costs (3662 ± 3186 €, 5316 ± 6139 €, 6021 ± 4892 €, and 8461 ± 8515 €; P < 0.001) increased continuously in Rutherford 1-3, 4, 5, and 6. While only 49% of the patients suffered from CLI, these produced 65% of in-hospital costs (141 million €), and 56% during follow-up (336 million €). CONCLUSION Regardless of recent advances in PAD treatment, current outcomes remain poor especially in CLI. Despite overwhelming evidence for reduction of limb loss by revascularization, CLI patients still received significantly less angiographies and revascularizations.

Recent trends in morbidity and in-hospital outcomes of in-patients with peripheral arterial disease: a nationwide population-based analysis

AIMS The prevalence of peripheral arterial disease (PAD) and especially of critical limb ischaemia (CLI) is announced to rise dramatically worldwide, with a considerable impact on the health care and socio-economic systems. We aimed to characterize the recent trends in morbidity and in-hospital outcome of PAD among all hospitalized patients in the entire German population between 2005 and 2009. METHODS AND RESULTS Nationwide data of all hospitalizations in Germany in 2005, 2007, and 2009 were analysed regarding the prevalence of PAD, comorbidities, endovascular (EVR) and surgical revascularizations (SR), major and minor amputations, in-hospital mortality, and associated costs. From 2005 to 2009, total PAD cases increased by 20.7% (from 400 928 to 483 961), with an increase of CLI subset from 40.6 to 43.5%. Total EVR increased by 46%, while thromb-embolectomy, endarterectomy, and patch plastic increased by 67, 42, and 21%, respectively. Peripheral bypasses decreased by 2%. Major amputation decreased from 4.6 to 3.5%, while minor amputation slightly increased from 4.98 to 5.11%. The crude overall in-hospital mortality remained unchanged in claudicants (2.2%), while it decreased from 9.8 to 8.4% in CLI patients. However, mortality rate according to the Poisson model (n/1000 hospital residence days) increased significantly in claudicants (P < 0.001). Total reimbursement costs for PAD in-patient care increased by 21% with an average per case costs in 2009 of €4506 in a claudicant and €6791 in a CLI patient. CONCLUSION This population-based analysis documents the significant rise of PAD, particularly of the CLI subset, and highlights the malign prognosis associated with PAD as indicated by high amputation and in-hospital mortality rates.

The Risk of Acute Kidney Injury and Its Impact on 30-Day and Long-Term Mortality after Transcatheter Aortic Valve Implantation

Background. Transcatheter aortic valve implantation (TAVI) is widely used in high risk patients (pts) with aortic stenosis. Underlying chronic kidney disease implicates a high risk of postprocedural acute kidney injury (AKI). We analyzed its occurrence, impact on hospital stay, and mortality. Methods. 150 consecutive pts underwent TAVI in our institution (mean age 81 ± 7 years; logistic EuroSCORE 24 ± 15%). AKI definition was a creatinine rise of 26.5 μmol/L or more within 48 hours postprocedural. Ten patients on chronic hemodialysis were excluded. Results. AKI occurred in 28 pts (20%). Baseline creatinine was higher in AKI pts (126.4 ± 59.2 μmol/L versus 108.7 ± 45.1 μmol/L, P = 0.09). Contrast media use was distributed evenly. Both, 30-day mortality (29% versus 7%, P < 0.0001) and long-term mortality (43% versus 18%, P < 0.0001) were higher; hospital stay was longer in AKI pts (20 ± 12 versus 15 ± 10 days, P = 0.03). Predicted renal failure calculated STS Score was similar (8.0 ± 5.0% [AKI] versus 7.1 ± 4.0% [non-AKI], P = 0.32) and estimated lower renal failure rates than observed. Conclusion. AKI remains a frequent complication with increased mortality in TAVI pts. Careful identification of risk factors and development of more suitable risk scores are essential.

Amputations and mortality in in-hospital treated patients with peripheral artery disease and diabetic foot syndrome

AIMS The prevalence of diabetes mellitus (DM) and its associated complications such as peripheral artery disease (PAD) and diabetic foot syndrome (DFS) are increasing worldwide. We aimed to determine the contemporary acute and long-term outcome of patients with PAD and DFS in Germany. METHODS Nationwide, anonymized data of 40,335 patients hospitalized for PAD and/or DFS from the years 2009-2011 were analyzed and followed up until 2013. Patients were classified into 3 groups: DFS, PAD+DM and PAD without DM. In-hospital and long-term outcome (1156days, 95% CI 1.151-1.161) regarding major and minor amputation and mortality was assessed. Cumulative amputation-free survival and overall survival rates were calculated using Kaplan-Meier analysis. RESULTS The proportion of DFS, PAD+DM and PAD only was 17.3%, 21.5% and 61.2%, respectively. At index-hospitalization, DFS patients had the highest amputation (31.9% vs. 11.1% vs. 6.0%), yet the lowest revascularization rate (18.2% vs. 67.8% vs. 71.6%) compared to patients with PAD only and PAD+DM (P<0.001). Cumulative 4-year survival (57.4%, 60.8% and 70.0%) and amputation-free-survival (45.4%, 74.4% and 86.5%) were lowest for DFS followed by PAD+DM and PAD only (P<0.001). CONCLUSIONS Patients with diabetes, particularly those with DFS, have persistent high rates of limb amputation and of mortality in a real-world setting. Our data emphasize the need for further dedicated research to identify and target the underlying causes of the extraordinary poor outcome in this high risk population.

Impact of Peripheral Arterial Occlusive Disease on the Development of Contrast Medium-Induced Acute Kidney Injury

Background/Aims: Contrast medium-induced acute kidney injury (CI-AKI) is an important complication following the use of iodinated contrast media. It accounts for a significant number of hospital-acquired acute kidney injuries and is associated with increased in-hospital and long-term mortality and immense health care costs. We evaluated whether the presence of peripheral arterial occlusive disease (PAD) affects the incidence of CI-AKI following heart catheterization. Methods: The impact of PAD on the frequency of CI-AKI after heart catheterization was analysed in the prospective single-centre Dialysis-versus-Diuresis trial (January 2001 to July 2004). The patients were retrospectively divided into 3 subgroups: patients with coronary heart disease (CHD), patients with PAD and patients without PAD or CHD. Results: 412 patients were included (83.5% men, 29.1% diabetes mellitus, 4.9% ejection fraction <35%). Of these, 251 (60.9%) suffered from CHD but not from PAD, 77 (18.7%) from PAD and 84 (20.4%) had neither CHD nor PAD. After heart catheterization, 49 (11.9 %) patients developed CI-AKI. Patients with PAD suffered significantly more often from CI-AKI than those without PAD (32.7 vs. 16.8%, p = 0.008). Multivariate analyses by logistic regression confirmed PAD to be an independent predictor of a CI-AKI (odds ratio 2.013, 95% confidence interval 1.009-4.016, p = 0.047). The CHD was not significantly associated with CI-AKI. Conclusion: Patients with PAD significantly more often develop a CI-AKI after heart catheterization than those without PAD.

Association of CKD with Outcomes Among Patients Undergoing Transcatheter Aortic Valve Implantation

BACKGROUND AND OBJECTIVES Despitethe multiple depicted associations of CKD with reduced cardiovascular and overall prognoses, the association of CKD with outcome of patients undergoing transcatheter aortic valve implantation has still not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from all hospitalized patients who underwent transcatheter aortic valve implantation procedures between January 1, 2010 and December 31, 2013 in Germany were evaluated regarding influence of CKD, even in the earlier stages, on morbidity, in-hospital outcomes, and costs. RESULTS A total of 28,716 patients were treated with transcatheter aortic valve implantation. A total of 11,189 (39.0%) suffered from CKD. Patients with CKD were predominantly women; had higher rates of comorbidities, such as coronary artery disease, heart failure at New York Heart Association 3/4, peripheral artery disease, and diabetes; and had a 1.3-fold higher estimated logistic European System for Cardiac Operative Risk Evaluation value. In-hospital mortality was independently associated with CKD stage ≥3 (up to odds ratio, 1.71; 95% confidence interval, 1.35 to 2.17; P<0.05), bleeding was independently associated with CKD stage ≥4 (up to odds ratio, 1.82; 95% confidence interval, 1.47 to 2.24; P<0.001), and AKI was independently associated with CKD stages 3 (odds ratio, 1.83; 95% confidence interval, 1.62 to 2.06) and 4 (odds ratio, 2.33; 95% confidence interval, 1.92 to 2.83 both P<0.001). The stroke risk, in contrast, was lower for patients with CKD stages 4 (odds ratio, 0.23; 95% confidence interval, 0.16 to 0.33) and 5 (odds ratio, 0.24; 95% confidence interval, 0.15 to 0.39; both P<0.001). Lengths of hospital stay were, on average, 1.2-fold longer, whereas reimbursements were, on average, only 1.03-fold higher in patients who suffered from CKD. CONCLUSIONS This analysis illustrates for the first time on a nationwide basis the association of CKD with adverse outcomes in patients who underwent transcatheter aortic valve implantation. Thus, classification of CKD stages before transcatheter aortic valve implantation is important for appropriate risk stratification.

Long-Term Mortality After Invasive Angiography and Endovascular Revascularization in Patients With PAD Having Chronic Kidney Disease

Peripheral arterial disease (PAD) and chronic kidney disease (CKD) are associated with increased mortality rates. We assessed long-term outcomes of patients with PAD and CKD. Patients with PAD undergoing invasive angiography and/or endovascular revascularization between 2005 and 2010 were retrospectively classified into 5 CKD stages. A follow-up was performed and 572 patients were included, 116 patients (20%) had normal renal function, 245 were in CKD stage 2 (43%), 156 in CKD stage 3 (27%), and 55 in CKD stages 4 + 5 (10%). Diabetes mellitus, hypertension, and anemia were more frequent in higher CKD stages (P < .03). During follow-up (mean 1135 days; 95% confidence interval 1159-1259), cumulative mortality was 21% and increased with advanced CKD stages (9%, 16%, 29%, and 47%, respectively, P < .001). In multivariate Cox regression models, higher CKD stages were significantly associated with poor survival. Medication adherence for secondary prevention was significantly lower than recommended but irrespective of CKD stages. Kidney function is an independent predictor of worse long-term survival in patients with PAD. While standard medications were used less often than recommended, no differences between CKD stages were noted.

PCSK9 inhibition for LDL lowering and beyond – implications for patients with peripheral artery disease

Low-density lipoprotein cholesterol (LDL-C) has been proven to be a causal factor of atherosclerosis and, along with other triggers like inflammation, the most frequent reason for peripheral arterial disease. Moreover, a linear correlation between LDL-C concentration and cardiovascular outcome in high-risk patients could be established during the past century. After the development of statins, numerous randomized trials have shown the superiority for LDL-C reduction and hence the decrease in cardiovascular outcomes including mortality. Over the past decades it became evident that more intense LDL-C lowering, by either the use of highly potent statin supplements or by additional cholesterol absorption inhibitor application, accounted for an even more profound cardiovascular risk reduction. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a serin protease with effect on the LDL receptor cycle leading to its degradation and therefore preventing continuing LDL-C clearance from the blood, is the target of a newly developed monoclonal antibody facilitating astounding LDL-C reduction far below to what has been set as target level by recent ESC/EAS guidelines in management of dyslipidaemias. Large randomized outcome trials including subjects with PAD so far have been able to prove significant and even more intense cardiovascular risk reduction via further LDL-C debasement on top of high-intensity statin medication. Another approach for LDL-C reduction is a silencing interfering RNA muting the translation of PCSK9 intracellularly. Moreover, PCSK9 concentrations are elevated in cells involved in plaque composition, so the potency of intracellular PCSK9 inhibition and therefore prevention or reversal of plaques may provide this mechanism of action on PCSK9 with additional beneficial effects on cells involved in plaque formation. Thus, simultaneous application of statins and PCSK9 inhibitors promise to reduce cardiovascular event burden by both LDL-C reduction and pleiotropic effects of both agents.

The Impact of Chronic Kidney Disease on Hospitalized Patients With Peripheral Arterial Disease and Critical Limb Ischemia

Peripheral arterial disease (PAD) and chronic kidney disease (CKD) are major public health problems worldwide. Evaluations of large-scale data on morbidity, outcome, and costs in patients having PAD with CKD are essential. Cross-sectional nationwide population-based analysis of all hospitalizations for PAD during 2009 in Germany focused on the stage-related impact of CKD on morbidity, in-hospital mortality, amputations, length of hospital stay, and health-related expenditure. The total number of hospitalizations was 483 961. Of those, 132 993 (27.5%) had CKD. Chronic kidney disease caused 1.8-fold higher amputation rate (P < .001) with a stepwise increasing rate with higher CKD stage. Chronic kidney disease doubled in-hospital mortality of patients with PAD (7.8%; n = 10 421) versus 4.0% (n = 14 174, P < .001) with a stepwise increasing risk with higher CKD stage (P < .001). The highest in-hospital mortality occurred in patients with coprevalence of CKD stage 4 and Fontaine stage IV (16.4%, n = 1176, P < .001). Chronic kidney disease caused 15% higher costs and 21% increased length of stay compared to the whole PAD cohort. This analysis demonstrates the stage-related influence of CKD on morbidity, in-hospital mortality, amputations, length of hospital stay, and reimbursement costs of hospitalized patients with PAD.

Impact of diabetes type on treatment and outcome of patients with peripheral artery disease

Background: The prevalence of diabetes mellitus and its associated complications such as peripheral artery disease is increasing worldwide. We aimed to explore the distinct impact of type 1 diabetes mellitus and type 2 diabetes mellitus on treatment and on short- and long-term outcome in patients with peripheral artery disease. Methods: Retrospective analysis of anonymized data of hospitalized patients covered by a large German health insurance. Assessment of patient’s characteristics (comorbidities, complications, etc.) and outcome using multivariable Cox regression and Kaplan–Meier curves. Results: Among 41,702 patients with peripheral artery disease, 339 (0.8%) had type 1 diabetes mellitus and 13,151 (31.5%) had type 2 diabetes mellitus. Patients with diabetes mellitus had more comorbidities and complications than patients without diabetes mellitus (p < 0.001). Type 1 diabetes mellitus patients exhibited the highest risk for limb amputation at 4-year follow-up (44.6% vs 35.1%, p < 0.001), while type 2 diabetes mellitus patients had higher mortality than type 1 diabetes mellitus (43.6% vs 31.0%, p < 0.001). Conclusion: Although the fraction of type 1 diabetes mellitus among patients with peripheral artery disease and diabetes mellitus is low, it represents a subset of patients being at particular high risk for limb amputation. Research focused on elaborating the determinants of limb amputation and mortality in peripheral artery disease patients with diabetes mellitus is warranted to improve the poor prognosis of these patients.