Eva Freisinger

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.

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.

Low Rates of Revascularization and High In-Hospital Mortality in Patients With Ischemic Lower Limb Amputation: Morbidity and Mortality of Ischemic Amputation.

Background: To assess the nationwide contemporary burden of cardiovascular risk factors, comorbidities, and in-hospital mortality in patients with lower limb amputation (LLA) due to peripheral arterial disease and critical limb ischemia (CLI) in Germany. Methods: German nationwide data for 2005 and 2009 were analyzed regarding in-hospital rates of major and minor ischemic LLA, risk factors, comorbidities, surgical and endovascular revascularizations, and in-hospital mortality. Results: In 2005, a total of 22 479 major (7.8%) and 28 262 minor (9.8%) LLAs were performed with a relative decrease of −21.8% in major LLA, yet with a relative increase of +2% in minor LLA rate in 2009. The overall revascularization rate before amputation was 46% in 2005 and 57% in 2009. In-hospital mortality for non-CLI, minor, and major amputees was 3.3%, 4.6%, and 19.8%, respectively (P < .001 for major vs minor LLA and non-CLI). Conclusion: The total number of ischemic LLA and amputation-related in-hospital mortality remains high in Germany in the 21st century. The poor outcome of patients with CLI might in part be due to underuse of revascularizations prior to amputation.

Atrial fibrillation is a risk marker for worse in-hospital and long-term outcome in patients with peripheral artery disease

OBJECTIVES To investigate the relevance of atrial fibrillation or flutter (AF) for outcome of patients who are hospitalized for peripheral artery disease (PAD) and/or critical limb ischemia (CLI). METHODS AND RESULTS We compared baseline data, co-morbidities, procedural data as well as in-hospital and long-term outcome of 41,882 patients who were hospitalized with PAD or CLI between 2009 and 2011 according to whether they did or did not have atrial fibrillation/flutter. Follow-up was available until December 2012. Of these, 5622 patients (13.4%) had AF. AF patients were significantly older (78±9 vs. 70±11years) and had significantly more comorbidities, such as diabetes (40.8 vs. 31.1%), chronic kidney disease (40.1 vs. 19.0%), coronary artery disease (38.0 vs. 23.0%) and chronic heart failure (26.9 vs. 7.2%, each p<0.001). They had more advanced PAD as shown by higher Rutherford classes. In-hospital complications including acute renal failure, myocardial infarction, stroke sepsis and death occurred significantly more often (each p<0.001). Duration of hospital stay was significantly longer and costs were markedly higher in patients with AF (each p<0.001). Using multivariate Cox regression analyses regarding long-term outcomes, AF was an independent predictor for death (HRR 1.46; 95% CI 1.39-1.52, p<0.001), ischemic stroke (HRR 1.63; 95% CI 1.44-1.85) and amputation (HRR 1.14; 95% CI 1.07-1.21). CONCLUSION Presence of AF in patients admitted for PAD and CLI is associated with worse in-hospital and long-term outcome than in patients without AF. This effect was independent of numerous other comorbidities and stage of vascular disease.

Restenosis after endovascular revascularization in peripheral artery disease

Endovascular revascularization (EVR) plays a leading role in the therapy of peripheral artery disease. The acute success rates of EVR in all anatomic territories and of all TASC lesions are excellent (> 95%). However, the occurrence of restenoses after EVR such as percutaneous transluminal angioplasty and particularly after stenting, poses a substantial limitation to the success of the procedure. Influenced by patients comorbidities, the severity of arteriosclerotic disease, lesion length and morphology as well as the techniques and devices used for EVR, the long-term outcome of EVR deteriorates markedly from the aortoiliac to the infrapopliteal segments of the lower limbs. The development of drug-coated balloons and drug-eluting stents reduced the occurrence of restenosis leading to considerably improved primary patency rates in the femoropopliteal segments. This review aims to provide an overview about the underlying mechanisms and current relevance of the various options in the field of EVR with regard to the rate of restenosis.

Peripheral artery disease is associated with high in-hospital mortality particularly in males with acute myocardial infarction in a nationwide real-world setting.

BACKGROUND Patients with peripheral arterial disease (PAD) are at high risk for cardiovascular morbidity and mortality. The objective of this nationwide analysis was to explore the association of PAD with in-hospital mortality in patients hospitalized for acute myocardial infarction (AMI). PATIENTS AND METHODS Data on all in-patient hospitalizations in Germany are continuously transferred to the Federal Statistical Office (DESTATIS), as required by federal law. These case-based data on AMI in the years 2005, 2007 and 2009 were analyzed regarding ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) as the primary diagnoses and concomitant PAD as the secondary diagnosis with respect to age and gender related disparity. RESULTS We analyzed 619,103 AMI cases, including 270,026 (43.6 %) with STEMI and 349,077 (56.4 %) with NSTEMI. The PAD ratio was 3.4 % in STEMI and 5.7 % in NSTEMI. In STEMI, in-hospital mortality was 15.6 % in cases with PAD vs. 12.0 % without, and 12.0 % vs. 9.8 % in NSTEMI, respectively (P < 0.001; 2009). Although female gender was associated with a significantly higher in-hospital mortality, the presence of PAD particularly negatively affected in-hospital mortality in men (+ 60 % male vs - 11 % female in STEMI; + 33 % male vs - 3 % female in NSTEMI). CONCLUSIONS Our data demonstrate the adverse impact of concomitant PAD on in-hospital mortality in AMI, in a large-scale, real-world scenario. Further research, particularly with a focus on gender, is needed to identify diagnostic and therapeutic measures to reduce the remarkably high in-hospital mortality of AMI patients with concomitant 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.

Prevalence and impact of critical limb ischaemia on in-hospital outcome in transcatheter aortic valve implantation in Germany

AIMS Peripheral artery disease (PAD) is common in patients with aortic valve stenosis (AS). This study sought to assess the prevalence of critical limb ischaemia (CLI) and its impact on in-hospital outcome in patients undergoing transcatheter aortic valve implantation (TAVI) for severe AS. METHODS AND RESULTS All isolated TAVI procedures for AS in Germany between 2007 and 2013 were analysed regarding the stage-specific prevalence of PAD, comorbidities, in-hospital complications and mortality using diagnostic and procedural codes. Among 32,044 patients with TAVI, 3,375 (10.5%) had PAD and 654 (2.0%) CLI. TAVI patients with PAD, particularly those with CLI, had a higher incidence of periprocedural stroke, bleeding and acute kidney injury (p<0.001). The overall in-hospital mortality among TAVI without PAD, non-CLI PAD and CLI was 6.1%, 8.4% and 14.7%, respectively (p<0.001). In a multivariate logistic regression analysis, CLI was an independent predictor of in-hospital mortality (odds ratio 1.96, 95% confidence interval 1.56-2.47; p<0.001). CONCLUSIONS In patients undergoing TAVI, the presence of PAD is associated with an increased risk of periprocedural complications, while only CLI independently predicts increased in-hospital mortality. Whether CLI represents a marker of general poor health status resulting in poor outcome or is a modifiable risk factor whose treatment prior to TAVI can improve the outcome requires prospective studies.

Outcome of patients with reduced ankle brachial index undergoing open heart surgery with cardiopulmonary bypass

OBJECTIVES In open heart surgery using cardiopulmonary bypass, perfusion of the lower extremities is markedly reduced which may induce critical ischaemia in patients with pre-existing peripheral artery disease. Whether these patients have an increased risk for amputation and should better undergo peripheral revascularization prior to surgery remains unclear. METHODS From 1 January 2009 to 31 December 2010, 785 consecutive patients undergoing open heart surgery were retrospectively included. In 443 of these patients, preoperative ankle brachial index (ABI) measurements were available. The cohort was divided into four groups: (i) ABI < 0.5, (ii) ABI 0.5-0.69, (iii) ABI 0.7-0.89 or (iv) ABI ≥ 0.9. Follow-up data of 413 (93.2%) patients were analysed with regard to mortality and amputations. RESULTS The groups differed significantly in terms of age, cardiac risk factors, performed cardiac surgery and renal function. Postoperative delayed wound healing was significantly associated with lower ABI (25.9, 15.2, 27.0 and 9.6% in Groups I-IV, respectively, P = 0.003), whereas 30-day mortality was not significantly higher in patients with lower ABI (0, 4.3, 8.1 and 3.9%, respectively, P = 0.4). Kaplan-Meier models showed a significantly lower long-term survival over 4 years in patients with reduced ABI (P = 0.001, long-rank test) while amputations occurred rarely with only one minor amputation in Group II (P = 0.023). CONCLUSIONS Patients with reduced ABIs undergoing heart surgery showed more wound-healing disturbances, and higher long-term mortality compared with those with normal ABIs. However, no perioperative ischaemia requiring amputation occurred. Thus, reduced ABIs were not associated with increased peripheral risks in open heart surgery but ABI may be helpful in selecting the site for saphenectomy to potentially avoid delayed healing of related wounds in legs with severely impaired arterial perfusion.