Alan G. Haynes

Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity Patient-Level Pooled Analysis of 6081 Patients

Background—Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. Methods and Results—In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ⩽11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03–1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18–2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96–2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64–1.22; P=0.45), without significant interaction with SYNTAX score ⩽11 or >11 for any of the end points. Conclusions—In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104.

Frequency, Timing, and Impact of Access-Site and Non–Access-Site Bleeding on Mortality Among Patients Undergoing Transcatheter Aortic Valve Replacement

OBJECTIVESnThe aim of this study was to examine the frequency, timing, and association of access-site and non-access-site bleeding with mortality in the setting of transcatheter aortic valve replacement (TAVR) during long-term follow-up.nnnBACKGROUNDnBleeding is frequent and associated with impaired prognosis in patients undergoing TAVR. It is currently unknown whether the site of bleeding differentially influences the outcomes of TAVR patients.nnnMETHODSnIn total, 926 consecutive patients undergoing TAVR from 2007 through 2014 were evaluated. Bleeding was assessed according to the Valve Academic Research Consortium 2 criteria. The primary outcome of interest was all-cause mortality up to 5 years of follow-up.nnnRESULTSnA total of 285 patients (30.7%) experienced at least 1 (minor, major, or life-threatening) bleeding event up to 5 years. Compared with patients not experiencing bleeding, the adjusted risk for all-cause mortality was significantly increased among patients with access-site (hazard ratio: 1.34; 95% confidence interval: 1.01 to 1.76; pxa0= 0.04) and non-access-site bleeding (hazard ratio: 2.08; 95% confidence interval: 1.60 to 2.71; pxa0< 0.001). However, non-access-site bleeding conferred a significantly higher risk for mortality compared with access-site bleeding (hazard ratio: 1.56; 95% confidence interval: 1.12 to 2.18; pxa0= 0.009). At multivariate analysis, female sex was a significant correlate of access-site bleeding, whereas chronic kidney disease and the Society of Thoracic Surgeons score were significantly associated with non-access-site bleeding.nnnCONCLUSIONSnAmong patients with severe aortic stenosis undergoing TAVR, access-site and non-access-site bleeding were independently associated with an increased risk for mortality, with the greatest risk related to non-access-site bleeding during long-term follow-up.

CPAP as treatment of sleep apnea after stroke: A meta-analysis of randomized trials

Objective To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effectiveness of continuous positive airway pressure (CPAP) in stroke patients with sleep disordered breathing (SDB). Methods In a systematic literature search of electronic databases (MEDLINE, Embase, and the Cochrane Library) from 1980 to November 2016, we identified RCTs that assessed CPAP compared to standard care or sham CPAP in adult patients with stroke or TIA with SDB. Mean CPAP use, odds ratios (ORs), and standardized mean differences (SMDs) were calculated. The prespecified outcomes were adherence to CPAP, neurologic improvement, adverse events, new vascular events, and death. Results Ten RCTs (564 participants) with CPAP as intervention were included. Two studies compared CPAP with sham CPAP; 8 compared CPAP with usual care. Mean CPAP use across the trials was 4.53 hours per night (95% confidence interval [CI] 3.97–5.08). The OR of dropping out with CPAP was 1.83 (95% CI 1.05–3.21, p = 0.033). The combined analysis of the neurofunctional scales (NIH Stroke Scale and Canadian Neurological Scale) showed an overall neurofunctional improvement with CPAP (SMD 0.5406, 95% CI 0.0263–1.0548) but with a considerable heterogeneity (I2 = 78.9%, p = 0.0394) across the studies. Long-term survival was improved with CPAP in 1 trial. Conclusion CPAP use after stroke is acceptable once the treatment is tolerated. The data indicate that CPAP might be beneficial for neurologic recovery, which justifies larger RCTs.

Transcatheter aortic valve thrombosis: incidence, clinical presentation and long-term outcomes

AimsnTo assess the incidence, management and long-term outcomes of transcatheter heart valve thrombosis (THVT).nnnMethods and resultsnBetween August 2007 and February 2016, 1396 patients were included in the Bern TAVI Registry and prospectively followed-up through echocardiographic and clinical evaluation. THVT was suspected in case of: (i) a mean transvalvular pressure gradient greater than 20u2009mmHg at transthoracic echocardiography, or (ii) an increase of more than 50% of the mean transvalvular pressure gradient compared with previous measurements or (iii) new symptoms or signs of heart failure with the presence of thrombus documented by transoesophageal echocardiography or multi-slice computed tomography. THVT occurred in 10 patients (0.71%) at variable time points after TAVI. Increased transvalvular pressure gradients were recorded in all patients and 7 out of 10 patients were symptomatic. Oral anticoagulant therapy (with vitamin K antagonists or non-Vitamin K antagonists) was initiated in all but two patients and resulted in normalization of transvalvular pressure gradients and amelioration of clinical status within 1u2009month. At long-term follow-up (between 10 and 25u2009months after valve thrombosis), echocardiographic findings were stable and no adverse events were reported.nnnConclusionnTHVT is rarely detected at routine clinical and echocardiographic evaluation after TAVI. Oral anticoagulation appears effective to normalize transvalvular gradients in the majority of cases with stable clinical and haemodynamic evolution during long-term follow-up.

Impact of cardiovascular risk factors on severity of peripheral artery disease

OBJECTIVEnThe development of peripheral artery disease is affected by the presence of cardiovascular risk factors. It is unclear, whether particular risk factors are leading to different clinical stages of peripheral artery disease. The aim of this retrospective cross-sectional study was to assess the association of cardiovascular risk factors with the presence of critical limb ischaemia.nnnMETHODSnThe study cohort was derived from a consecutive registry of patients undergoing endovascular therapy in a tertiary referral centre between January 2000 and April 2014. Patients undergoing first-time endovascular intervention for chronic peripheral artery disease of the lower extremities were included. Univariate and multivariate logistic regression models were used to assess the association of age, sex, diabetes mellitus, hypertension, dyslipidaemia, smoking, and renal insufficiency with critical limb ischaemia vs. intermittent claudication.nnnRESULTSnA total of 3406 patients were included in the study (mean age 71.7 ± 11.8 years, 2075 [61%] male). There was a significant association of age (OR 1.67, 95%-CI 1.53-1.82, p < 0.001), male gender (OR 1.23, 95%-CI 1.04-1.47, p = 0.016), diabetes (OR 1.99, 95%-CI 1.68-2.36, p < 0.001) and renal insufficiency (OR 1.62, 95%-CI 1.35-1.96, p < 0.001) with the likelihood of critical limb ischaemia. Smoking was associated with intermittent claudication rather than critical limb ischaemia (OR 0.78, 95%-CI 0.65-0.94, p = 0.010), while hypertension and dyslipidaemia did not show an association with critical limb ischaemia.nnnCONCLUSIONSnIn peripheral artery disease patients undergoing first-time endovascular treatment, age, male gender, diabetes, and renal insufficiency were the strongest predictors for the presence of critical limb ischaemia.

Patency of the arterial pedal–plantar arch in patients with chronic kidney disease or diabetes mellitus

Background: Patency of the pedal-plantar arch limits risk of amputation in peripheral artery disease (PAD). We examined patients without chronic kidney disease (CKD)/diabetes mellits (DM) [PAD-control], those with DM without CKD, and those with CKD without DM. Method: Uni- and multivariate logistic regression was used to assess association of CKD with loss of patency of the pedal–plantar arch and presence of tibial or peroneal vessel occlusion. Multivariate models adjusted for age, sex, hypertension, hyperlipidemia and smoking. Results: A total of 419 patients were included [age 75.2 ± 10.3 years, 288 (69%) male]. CKD nearly doubled the unadjusted odds ratio (OR) for loss of patency of the pedal–plantar arch. After adjustment, association remained significant for severe CKD [estimated glomerular filtration rate (eGFR) ≤ 29 ml/min compared with eGFR ≥ 60 ml/min, adjusted (adj.) OR 8.24 (95% confidence interval {CI} 0.99–68.36, p = 0.05)]. CKD was not related to risk of tibial or peroneal artery occlusion [PAD-control versus CKD, adj. OR 1.09 (95% CI 0.49–2.44, p = 0.83)] in contrast to DM [PAD–control versus DM, adj. OR 2.41 (95% CI 1.23–4.72, p = 0.01), CKD versus DM, adj. OR 2.21 (95% CI 0.93–5.22); p = 0.07)]. Conclusions: Below the knee (BTK) vascular pattern differs in patients with either DM or CKD alone. Severe CKD is a risk factor for loss of patency of the pedal–plantar arch.

Long-term oxygen therapy in COPD patients: population-based cohort study on mortality

Purpose Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and is associated with a growing and substantial socioeconomic burden. Long-term oxygen therapy (LTOT), recommended by current treatment guidelines for COPD patients with severe chronic hypoxemia, has shown to reduce mortality in this population. The aim of our study was to assess the standardized mortality ratios of incident and prevalent LTOT users and to identify predictors of mortality. Patients and methods We conducted a 2-year follow-up population-based cohort study comprising all COPD patients receiving LTOT in the canton of Bern, Switzerland. Comparing age- and sex-adjusted standardized mortality ratios, we examined associations between all-cause mortality and patient characteristics at baseline. To avoid immortal time bias, data for incident (receiving LTOT <6 months) and prevalent users were analyzed separately. Results At baseline, 475 patients (20% incident users, n=93) were receiving LTOT because of COPD (48/100,000 inhabitants). Mortality of incident and prevalent LTOT users was 41% versus 27%, respectively, p<0.007, and standardized mortality ratios were 8.02 (95% CI: 5.64–11.41) versus 5.90 (95% CI: 4.79–7.25), respectively. Type 2 respiratory failure was associated with higher standardized mortality ratios among incident LTOT users (60.57, 95% CI: 11.82–310.45, p=0.038). Conclusion Two-year mortality rate of COPD patients on incident LTOT was somewhat lower in our study than in older cohorts but remained high compared to the general population, especially in younger patients receiving LTOT <6 months. Type 2 respiratory failure was associated with mortality.

Predicting Mortality After Transcatheter Aortic Valve Replacement: External Validation of the Transcatheter Valve Therapy Registry Model

Background— The Transcatheter Valve Therapy (TVT) registry model was recently developed to predict the risk of in-hospital mortality in patients undergoing transcatheter aortic valve replacement. We sought to externally validate the model in an independent data set of consecutively enrolled patients in the Swiss Transcatheter Aortic Valve Implantation registry. Methods and Results— The original prediction model was retrospectively applied to 3491 consecutive patients undergoing transcatheter aortic valve replacement in Switzerland between February 2011 and February 2016. We examined model performance in terms of discrimination (Harrel C index) and calibration (Hosmer–Lemeshow goodness-of-fit test) for prediction of in-hospital and 30-day mortality and compared its predictive accuracy with the Society of Thoracic Surgeons Predicted Risk of Mortality score. Rates of in-hospital and 30-day mortality in the external validation cohort were 2.9% and 3.8%, respectively. The TVT registry model was found to have moderate discrimination (C index, 0.66; 95% confidence interval, 0.60–0.72 and C index, 0.67; 95% confidence interval, 0.62–0.72 for in-hospital and 30-day mortality, respectively) and good calibration. Compared with the Society of Thoracic Surgeons Predicted Risk of Mortality score, the TVT registry model demonstrated improved calibration for in-hospital (slope, 0.83; P=0.23 versus slope, 0.24; P<0.001, respectively) and 30-day (slope, 1.11; P=0.40 versus slope, 0.41; P<0.001, respectively) mortality. Conclusions— In a large, multicenter, non-US cohort of patients with transcatheter aortic valve replacement, the validation of the TVT registry model demonstrated moderate discrimination and good calibration for the prediction of in-hospital and 30-day mortality. As a result, the TVT registry model should be considered an alternative to the Society of Thoracic Surgeons Predicted Risk of Mortality score for decision making and assessment of early outcome in patients eligible for transcatheter aortic valve replacement.

Outcomes in Advanced Head and Neck Cancer Treated with Up-front Neck Dissection prior to (Chemo)Radiotherapy.

Objective Our aim was to compare outcomes with and without up-front neck dissection prior to (chemo)radiotherapy in head and neck squamous cell carcinoma. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods Outcomes of oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma cases with neck lymph node metastases treated from January 2001 to March 2012 were analyzed. Due to imbalances in baseline characteristics between groups treated with (n = 129) and without (n = 95) up-front neck dissection, propensity score matching was performed. Results Median follow-up was 48 months (range, 12-148). With up-front neck dissection, the hazard ratio for the primary end point, disease-free survival, was 0.63 (95% confidence interval: 0.37-1.06, P = .08). Up-front neck dissection reduced acute grade ≥3 toxicity significantly when xerostomia was excluded (odds ratio: 0.40, 95% confidence interval: 0.20-0.82, P = .012). Conclusion Our results indicate less acute treatment toxicity without any significant difference in terms of oncologic outcome with up-front neck dissection prior to (chemo)radiotherapy as compared with (chemo)radiotherapy alone. Well-designed randomized trials are required to verify this result and further investigate the impact of this strategy on late toxicity and oncologic outcome.

Baseline characteristics and patterns of care in testicular cancer patients: first data from the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS)

BACKGROUNDnThe majority of germ cell tumour (GCT) patients can be cured by orchiectomy followed by active surveillance or subsequent systemic and/or local treatments. There are various guidelines for a structured follow-up including radiographic and clinical examinations.nnnOBJECTIVEnThe Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS) prospectively evaluates follow-up, indicator of relapse and late toxicities. This is a descriptive analysis; we present baseline characteristics and treatment strategies for the first 299 patients with primary GCT or relapsed GCT after completion of treatment.nnnRESULTSnOf the patients included in this study, 192 (64.2%) had seminoma and 107 (35.8%) non-seminoma. Mean age was 41 years (standard deviation [SD] 11.7) for seminoma and 31 (SD 9.3) years for non-seminoma patients. Median tumour size was 3.5 cm (interquartile range 2.5¬‒5.0 and 2.3‒4.5 in seminoma and non-seminoma, respectively) in both histological groups. Among seminoma patients, 81 (42.2%) had primary tumours >4cm; 154 (80.2%) seminoma patients had stage I, 26 (13.5%) stage II and 12 (6.3%) stage III disease. Fifty-seven (53.3%) non-seminoma tumours were stage I, 29 (27.1%) stage II and 21 (19.6%) stage III. Marker-positive disease was present in 58 (30.2%) seminoma patients and 78 (72.9%) non-seminoma patients. Of 154 stage I seminoma patients, 89 (57.8%) chose active surveillance and 65 (42.2%) adjuvant chemotherapy. Twenty-six (45.6%) stage I non-seminoma patients had high-risk disease; 23 of these were treated with adjuvant chemotherapy and 3 chose active surveillance. Among the 30 (52.6%) low risk stage I patients, all opted for active surveillance. Twelve (46.2%) stage II seminoma patients had radiotherapy, 14 (53.8%) were treated with three to four cycles of chemotherapy. All stage III seminoma patients, and all stage II and III non-seminoma patients were treated with three to four cycles of chemotherapy. Treatment decisions were made at the respective centre. Eleven patients did not receive therapy that conformed with guidelines.nnnCONCLUSIONnIt is important to enrol GCT patients in prospective studies in general, but also in follow-up studies to assess baseline characteristics, oncological outcome, and long-term toxicity and to validate the performance of follow-up schedules. This is the first time that the distribution of disease, detailed baseline characteristics and the respective treatment of men with GCT is collected in a prospective manner in German speaking countries (Switzerland, Austria and Germany) and therefore patterns of care have been evaluated. SAG TCCS results will inform on future modifications of surveillance schedules and follow-up procedures.nnnTRIAL REGISTRATION NUMBERnNCT02229916 (Clinicaltrials.gov).