Transcatheter aortic valve implantation (TAVI) has shown promising results in patients with severe aortic stenosis (AS) at high risk for conventional heart surgery. The safety and efficacy of transapical aortic valve implantation using the JenaValve™, a second-generation TAVI device, were evaluated. The system consists of a tested porcine root valve mounted on a nitinol stent with feeler-guided positioning and clip fixation on the diseased leaflets.

This multicentre, prospective, single-arm study, conducted at seven German sites, enrolled 73 patients (mean age 83.1 ± 3.9), European System for Cardiac Operative Risk Evaluation (EuroSCORE) (28.4 ± 6.5%) of whom 67 patients underwent elective TAVI. Three sizes were used for annular diameters up to 23 mm (n = 21), 25 mm (n = 31) and 27 mm (n = 15). Clinical and echocardiographic evaluations were performed at baseline, post-procedure, discharge and 30 days, and also at 3, 6 and 12 months. The primary endpoint was all-cause mortality at 30 days. Secondary endpoints were procedural success, major adverse cardiac and cerebrovascular events and echocardiographic performance.

TAVI with the JenaValve™ device was successful in 60 patients (procedural success rate 89.6%). The overall mortality at 30 days was 7.6%. Conversion to surgery was necessary in four patients (6%), two patients underwent valve-in-valve implantations (3%), one patient was withdrawn per protocol after conversion to TAVI using a balloon-expandable valve (1.5%) since the patient did not receive the study device. Perioperative stroke occurred in two cases (3%). Pacemaker implantation for new onset conduction disorders was necessary in six patients (9.1%). No ostial coronary obstructions were seen. Post-procedure TAVI resulted in favourable reduction of mean transvalvular gradients (40.6 ± 15.9 vs. 10.0 ± 7.2 mmHg, P < 0.0001) and increase in valve opening area (0.7 ± 0.2 vs. 1.7 ± 0.6 cm², P < 0.0001). The majority of successfully treated patients revealed no or minimal paravalvular aortic regurgitation (86.4%); none of the patients had severe post-procedural regurgitation (>2+).

Transapical JenaValve™ implantation was safe and effective in the treatment of severe AS in elderly patients at high risk for surgery. Active clip fixation on the native leaflets and anatomically correct feeler-guided positioning led to good functionality and prevented ostial coronary impairment. Implantation without the need for rapid pacing prevented haemodynamic compromise during valve implantation.

The optimal timing of the Fontan staging for a univentricular heart and its impact on growth remains debateable. In a Fontan cohort, the influence of staged interventions and patient factors on somatic development was explored.

We reviewed 64 total cavopulmonary connection (TCPC) patients treated since 1992. Serial anthropometric parameters recorded from birth to the latest follow-up (mean 12.5 ± 6.1 years) and at each intervention [neonatal surgery, bidirectional cavopulmonary anastomosis (BCPA), TCPC, catheter treatment] were converted to z-scores. The influence of saturation, heart failure treatment and surgery intervals on growth was determined.

The mean z-scores for weight and height changed significantly at each surgery up to the TCPC (–0.3 ± 1.2 and 0 ± 1 at birth, –1.3 ± 1.9 and –0.9 ± 1.7 at neonatal surgery, –2.1 ± 1.2 and –1.6 ± 1.3 at the BCPA, –1.2 ± 1.3 and –0.7 ± 1.4 at the TCPC for weight and height, respectively; P < 0.05 for each interval), with the largest decline before the BCPA, and the most marked improvement before the TCPC. Z-scores did not change significantly after the TCPC. Younger age at the BCPA had a positive influence on the weight z-score at the TCPC (P < 0.05); somatic growth at the latest follow-up (FU) was negatively influenced by heart failure treatment (P < 0.05).

Body growth is severely impaired in Fontan patients. A close interstage follow-up between the first surgery and the BCPA must be targeted at optimizing nutritional support to counter the important growth retardation occurring before the BCPA. The better catch-up growth at the TCPC when the BCPA is performed earlier in life supports the current trend to perform the BCPA at a younger age. Heart failure treatment after a Fontan completion is independently associated with decreased late somatic development.

To explore the feasibility of evaluating the aortopulmonary collateral flow (APCF) and pulmonary vascular growth of patients who underwent bidirectional Glenn shunting (BGS) using phase-contrast magnetic resonance imaging (PC-MRI) and contrast-enhanced magnetic resonance imaging (CE-MRI).

Blood flow measurements of the great vessels of the body were recorded in 22 post-BGS patients using 3.0 T PC-MRI. Right and left pulmonary blood flow (Q_P), stroke volume (SV) of the ascending aorta (Q_S), blood flow of descending aorta (Q_d) and venous return of the superior and inferior venae cavae (Q_V) per minute were calculated using the Report Card software. APCF was equal to the difference between Q_S and Q_V. The parameters for pulmonary vascular growth were assessed using CE-MRI. The relationship between pulmonary vascular growth and APCF was evaluated using correlation analysis. A comparative analysis was conducted between the MRI results and the results of five cases who underwent cardiac catheterization and 10 cases who underwent angiography.

Estimated APCF ranged from 0.23 to 1.63 l/(min/m²), accounting for 5–44% of Q_S. Morphologic abnormalities such as pulmonary stenosis, dilatation and thrombosis were clearly visualized through CE-MRI. Significant differences in individual pulmonary artery growth were observed. A significant negative correlation was found between APCF and the pulmonary artery index (PAI; r = –0.461, P = 0.031) when the McGoon rate was 2.04 ± 0.59 and the PAI was 253.27 ± 85.86 mm²/m². Good consistency or relativity was found between cardiac catheterization, angiography and MRI.

Assessing the APCF and parameters for pulmonary vascular growth in patients who underwent BGS is feasible using 3.0 T PC-MRI integrated with CE-MRI, which may play an important role in clinical and therapeutic decision-making and prognostic evaluation.

Advanced age is not a barrier to cardiac surgery, with reports demonstrating excellent outcomes, but the effect of age on more complex surgery has not been studied. We assessed the outcomes of pulmonary endarterectomy (PEA) surgery in patients aged >70.

A retrospective review of consecutive patients who underwent PEA between January 2006 and March 2011 at a national referral centre. The total cohort was dichotomized according to age on the day of surgery, either below or above 70 years. Outcomes were in-hospital mortality, overall survival and the length of ICU and hospital stays.

Four hundred and eleven patients underwent PEA during the 5-year period. The mean age was 56.9 years (range, 17–84 years). The in-hospital mortality was 14 of 308 (4.6%) for patients <70 years compared with 8 of 103 (7.8%) for patients ≥70 years (P = 0.21). The overall survival at 1, 2 and 3 years was 91.4, 89.9 and 87.7% in the <70-year old group and 85.9, 84.1 and 84.1% in the >70-year old group (log-rank test, P = 0.07), respectively. The length of ICU and in-hospital stays was longer in the >70-year old group, by 1 and 2 days, respectively (P = 0.005 and 0.001).

PEA surgery in patients ≥70 years is safe and carries a comparable risk of early mortality in younger patients, but there is an increase in resource use due to longer ICU and hospital stays. Advanced age should be taken into consideration when assessing suitability for PEA, but age per se should not be a contraindication to surgery.

Postoperative acute exacerbation (PAE) of idiopathic pulmonary fibrosis (IPF) is a serious complication that is hard to treat. Therefore, it is important to manage IPF patients in such a way as to avoid PAE. Conversely, the relationship between postoperative acute lung injury and perioperative fluid administration has been reported. Herein, we analyse the perioperative risk factors of PAE of IPF, including fluid management.

Fifty-two patients diagnosed as having clinical IPF who underwent pulmonary resection (segmentectomy, lobectomy or bilobectomy) for primary lung cancer were analysed retrospectively. Preoperative predictive factors and perioperative management items, especially fluid management, were evaluated.

The incidence of PAE of IPF was 13.5% (7 of 52 patients). Six patients (85.7%) died of respiratory failure induced by uncontrollable PAE of IPF. Upon univariate analysis, the amount of the intraoperative fluid infused (ml/kg/h), the intraoperative fluid balance (ml/kg/h) and the preoperative C-reactive protein (CRP) level were found to be significantly higher in IPF patients who developed PAE than in those who did not. A multivariate logistic regression analysis showed that the intraoperative fluid balance and the preoperative CRP were prognostic factors for PAE of IPF [P = 0.026, odds ratio (OR) = 1.312 and P = 0.048, OR = 1.280, respectively].

To prevent PAE of IPF, intraoperative management that minimizes intravenous fluid administration is essential. Moreover, caution is particularly important in patients with preoperative evidence of inflammation.

The CARMAT total artificial heart (TAH) is an implantable, electro-hydraulically driven, pulsatile flow device with four bioprosthetic valves. Its blood-pumping surfaces consist of processed bioprosthetic pericardial tissue and expanded polytetrafluorethylene (ePTFE), potentially allowing for the reduction of anti-coagulation. This pre-clinical study assessed the in vitro haemocompatibility of these surfaces.

Coupons of pericardial tissue and ePTFE were placed in closed tubular circuits filled with 12.5 ml of fresh human blood exposed to the pulsatile flow at 120 ml/min for 4 h (37°C). Silicone- and heparin-coated polyvinyl chloride (PVC) tubes served as positive and negative controls, respectively. Fresh blood from six donors was used to fill four sets of 12 circuits. Blood samples were taken at baseline and from each circuit after 4 h. Coupons of materials were examined with scanning electron microscopy.

The platelet count was 202 ± 45 10⁹ l^–1 at baseline. Four hours after circulation, the platelet counts were 161 ± 30 10⁹ l^–1 (compared with baseline, P = 0.0207) for pericardial tissue, 162 ± 35 10⁹ l^–1 (P = 0.0305) for ePTFE and 136 ± 42 10⁹ l^–1 for positive controls (P = 0.0021). Baseline plasma fibrinogen was 2.9 ± 0.5 mg/dl compared with 3.0 ± 0.5 mg/dl for pericardial tissue and 3.1 ± 0.7 mg/dl for ePTFE, indicating no marked fibrinogen consumption. Thromboxane B2 levels for positive controls were 33.3 ± 8.7 ng/ml compared with 16.2 ± 11.5 ng/ml for pericardial tissue (P = 0.0015) and 15.2 ± 4.7 ng/ml for ePTFE (P < 0.0001). Platelet adhesion was 2.87 ± 1.01 10⁹ cm^–2 for positive controls compared with 1.06 ± 0.73 10⁹ cm^–2 for pericardial tissue (P < 0.0001) and 0.79 ± 0.75 10⁹ cm^–2 for ePTFE (P < 0.0001). Thrombin–antithrombin III complex levels were 3.8 ± 0.5 μg/ml for positive controls compared with 1.9 ± 0.9 for pericardial tissue (P < 0.0001) and 2.1 ± 1.0 for ePTFE (P < 0.0001). With an electro-microscopic examination at x600, only small depositions of platelets, erythrocytes and fibrin were noticed on the pericardial tissue samples and ePTFE samples. Silicone surfaces showed marked areas of thrombi, and PVC tubings a thin protein layer.

Haemocompatibility of the TAH blood-contacting surfaces was confirmed by in vitro studies showing a limited consumption of fibrin, limited thromboxane B2 release and platelet adhesion, and minor blood cell depositions on the surfaces. These results will be validated in clinical studies, with the aim of reducing anti-coagulation when using the CARMAT TAH.

The increasing relevance of the cancer stem cell (CSC) hypothesis and the impact of CSC-associated markers in the carcinogenesis of solid tumours may provide potential prognostic implications in lung cancer. We propose that a collective genetic analysis of established CSC-related markers will generate data to better define the role of putative CSCs in lung adenocarcinoma (LAC).

Sixty-four paired tumour and non-tumour biopsies from LAC patients were included in this study. Using the quantitative reverse transcriptase–polymerase chain reaction, we assessed the expression profiles of established CSC-related biomarkers: octamer-binding transcription factor 4 (OCT4A), CD133, aldehyde dehydrogenase (ALDH), BMI-1, ATP-binding cassette subfamily G, member 2 (ABCG2), SRY (sex-determining region Y)-box 2 (SOX2) and uPAR, and evaluated their relation to clinicopathological parameters and disease prognosis.

All of the above-mentioned CSC-related markers were detectable in both tumour and corresponding normal tissues. Importantly, expression levels of OCT4A, CD133, BMI-1, SOX2 and uPAR were significantly higher (OCT4A, P = 0.0003; CD133, P = 0.002; BMI-1, P = 0.04; SOX2, P = 0.0003; uPAR, P = 0.03) in the tumour compared with those in the non-tumour tissues. By contrast, the quantities of ACBG2 and ALDH were markedly reduced (ACBG2, P = 0.0006; ALDH, P = 0.007) in the tumour relative to those in the normal biopsies. Using multivariate analysis, elevated ALDH and CD133 revealed significant associations in tumour stage (ALDH, P = 0.03; CD133, P = 0.007) and differentiation (ALDH, P = 0.03; CD133, P = 0.018). We observed that ALDH and OCT4A were associated with nodal status (ALDH, P = 0.05; OCT4A, P = 0.03) having lower mRNA levels in tumours with lymph node metastasis, N+, compared with that in N0. High OCT4A levels were significantly correlated with tumour size of <3 cm, decrease in tumours >3 cm (P = 0.03). Kaplan–Meier correlation analyses, showed that OCT4A and CD133 were correlated to short disease-free intervals (OCT4A, P = 0.047; CD133, P = 0.033) over a period of 29 months.

Our study reveals that CSC-associated markers: OCT4A, CD133 and ALDH are involved in the initial phase of carcinogenesis of LAC, and can be used as predictors of early stage LAC and poor disease-free intervals. In addition, this work validates the relevance of the CSC hypothesis in LAC.

Patients undergoing transapical aortic valve implantation (TA-AVI) are usually over 80 years old and have a high prevalence of chronic kidney disease. However, transcatheter valve therapies require the use of contrast injections with the risk of nephrotoxicity. The aim of this study was to evaluate post-operative kidney function and survival in patients with pre-existing renal impairment with regard to the amount of contrast media used during TA-AVI.

From January 2008 to March 2011, 50 patients (52% females, mean age 80.7 ± 5.3 years) with a serum creatinine level of >1.3 mg/dl were investigated. Patients receiving a dose of <100 ml of a contrast agent (low-dose group, n = 24) were separated from those who received >100 ml of a contrast agent (high-dose group, n = 26). An acute contrast-induced nephropathy (CIN) was defined as a serum creatinine increase of 0.5 mg/dl or by >25% of a baseline value within 48 h from contrast medium administration. Patients in both groups had similar characteristics in terms of age, sex, body mass index and comorbidities.

The median pre-contrast creatinine was 1.67 (1.37–1.83) mg/dl in the low-dose group and 1.51 (1.26–1.98) mg/dl in the high-dose group (P = 0.76). The post-contrast creatinine at 48 h was 1.53 (1.33–2.05) and 2.29 (1.67–2.86) mg/dl in the groups receiving low- and high-dose contrast agents, respectively (P = 0.007). CIN occurred in 41.7% (n = 10) of patients in the low-dose contrast group and in 69.2% (n = 18) in the high-dose contrast group (P = 0.046). Haemodialysis is necessary for 16.7% of the low-dose group and 38.5% of the high-dose group (P = 0.12). Trends towards longer intensive care unit and hospital stay were seen in patients with an extensive use of contrast media [4.3 (2.5–6.5) vs. 5 (3–7.8) days and 12 (9–14.3) vs. 13 (9–18) days, P = 0.091 vs. P = 0.546, respectively]. Regarding death, 3-month and 3-year mortality were significantly higher in the high-dose group (8.3 vs. 30.8%, P = 0.036 and 25 vs. 61.5%, P = 0.004, respectively).

Our results indicate a possible association between higher CIN and mortality rate and the extensive use of contrast media during TA-AVI among high-risk patients with pre-existing renal impairment.