Tumor necrosis factor alpha—an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BackgroundSystemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre‐interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF‐α in TAVR.MethodsA total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post‐intervention, 4, 5, and 7 days post‐intervention, and 1, 3, and 6 months post‐TAVR.ResultsIn a univariate Cox proportional hazard analysis, plasma concentrations of TNF‐α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000–1.004), p = 0.028; after 5d: HR 1.003 (1.001–1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut‐offs were calculated. Patients above the cut‐off for TNF‐α after 5d had a significantly worse 12‐month mortality than patients below the cut‐off (18.8% vs. 2.8%, p = 0.046).ConclusionPlasma levels of TNF‐α after 24 h and 5 days were independently associated with 12‐month mortality in patients undergoing TAVR. Thus, TNF‐α could represent a novel biomarker for enhanced risk stratification in these patients.     

Troponin release following endurance exercise: is inflammation the cause? a cardiovascular magnetic resonance study

Background

The aetiology and clinical significance of troponin release following endurance exercise is unclear but may be due to transient myocardial inflammation. Cardiovascular magnetic resonance (CMR) affords us the opportunity to evaluate the presence of myocardial inflammation and focal fibrosis and is the ideal imaging modality to study this hypothesis. We sought to correlate the relationship between acute bouts of ultra endurance exercise leading to cardiac biomarkers elevation and the presence of myocardial inflammation and fibrosis using CMR.

Methods

17 recreation athletes (33.5 +/- 6.5 years) were studied before and after a marathon run with troponin, NTproBNP, and CMR. Specific imaging parameters to look for inflammation included T2 weighted images, and T1 weighted spin-echo images before and after an intravenous gadolinium-DTPA to detect myocardial hyperemia secondary to inflammation. Late gadolinium imaging was performed (LGE) to detect any focal regions of replacement fibrosis.

Results

Eleven of the 17 participant had elevations of TnI above levels of cut off for myocardial infarction 6 hrs after the marathon (0.075 +/- 0.02, p = 0.007). Left ventricular volumes were reduced post marathon and a small increase in ejection fraction was noted (64+/- 1% pre, 67+/- 1.2% post, P = 0.014). Right ventricular volumes, stroke volume, and ejection fraction were unchanged post marathon. No athlete fulfilled criteria for myocardial inflammation based on current criteria. No regions of focal fibrosis were seen in any of the participants.

Conclusion

Exercise induced cardiac biomarker release is not associated with any functional changes by CMR or any detectable myocardial inflammation or fibrosis.     

The groin first approach for transcatheter aortic valve implantation: are we pushing the limits for transapical implantation?

Objective

Transcatheter aortic valve implantation (TAVI) is a therapeutic option for old and multimorbid patients with severe aortic stenosis. When applying the groin first approach by transfemoral implantation, patients in the transapical group are highly selected with even higher morbidity. We report outcome of the transapical group.

Methods

Between April 2008 and May 2011, 267 patients underwent TAVI through either a transfemoral (n = 201 CoreValve, n = 33 Edwards Sapien prostheses; mean age 81 ± 6 years, logistic EuroSCORE 19.5 ± 12.6 %; 4–76, STS score 7.2 ± 4 %; 1.5–28.9) or transapical approach (n = 33 Edwards Sapien prostheses; mean age 80 ± 1 years, logistic EuroSCORE 31.6 ± 17.1 %; 9.4–69.1, STS score 12.8 ± 7.1 %; 2.5–28.8). The transapical access was chosen only when transfemoral implantation was not possible.

Results

EuroSCORE and STS score were significantly higher in the transapical group (p = 0.001, respectively). A 30-day survival was comparable with 87.9 % in the transapical versus 92 % in the transfemoral group (p = 0.52). In the transapical group, female gender was predominant (n = 23; 70 %). Eight patients underwent previous cardiac surgery. All transapical implantations were successful. No bleeding or neurological complications occurred. Six patients required postoperative pacemaker implantation. Cardiac decompensation with concomitant pneumonia was the underlying cause for early mortality, except for one patient with abdominal malperfusion. Follow-up (0–37 months) was complete in 100 %, nine patients died after 30 days postoperatively (6 cardiac and 3 non-cardiac related). Echocardiography revealed good valve function with not more than mild paravalvular incompetence.

Conclusions

Groin first approach is reasonable due to less invasive implantation technique. However, despite even higher predicted mortality, transapical aortic valve implantation is non-inferior to transfemoral approach.     

The Ross operation: utilization of the patient’s own pulmonary valve as a replacement device for the diseased aortic valve

Prosthetic heart valves have been outpaced by progress in cardiac surgery. Early biologic valve protheses consisted of tissues mounted on a rigid stent, and did not require anticoagulation, but rarely survived two decades. Subsequently, durable mechanical valve prostheses dominated despite, the requisite anticoagulation. The mechanical design remains imperfect, with obstruction to flow, turbulance, hematological changes and also, occasionally audible clicks. Reports documenting superior function for cryopreserved human aortic heart valves (homografts) without these problems, albeit with limited durability, followed. The marketing of ‘stentless biologic valves’, mimicking these attributes was a reaction to the shortage of homografts. These imperfections explain the rediscovery of the Ross operation, in which the patient’s pulmonary valve (autograft) is excised to replace the aortic valve. The autograft is living tissue, complete with attributes of a healthy heart valve, including growth and durability. The pulmonary valve, where lower pressure and oxygen saturation retards degeneration, is subsituted with a pulmonary homograft. The Ross operation is exacting and leaves the patient with two potentially malfunctioning valves.     

Dysfunction of alveolar macrophages after cardiac surgery and postoperative pneumonia? - an observational study

Introduction

Patients undergoing cardiac surgery have an increased risk of postoperative pneumonia. Pulmonary immune dysfunction might be a contributing factor. We therefore determined changes of the surface molecules on alveolar macrophages (AMs). To characterize modulation in patients with pneumonia we correlated these changes to the development of postoperative pneumonia.

Methods

After ethical approval and written informed consent, 33 patients undergoing elective coronary bypass grafting surgery were included in this observational study. Peripheral blood cells and alveolar lavage fluid were collected directly after induction of anesthesia and two hours after separation from cardiopulmonary bypass (CPB). Human leukocyte antigen-DR (HLA-DR) and toll-like receptors (TLR) 2/4 expression on monocytes and AM were assessed by flow cytometry. A total of three patients developed postoperative pneumonia determined according to the criteria of the Center of Disease Control. Statistical analysis was performed with the Mann–Whitney-U test and Wilcoxon test.

Results

We found significant changes of phenotypic and functional immune markers on AMs after cardiac surgery. HLA-DR expression on peripheral blood monocytes and AMs was significantly reduced compared to baseline in all patients (each approximately 30%). After surgery patients who developed postoperative pneumonia revealed a trend of stronger reduction of HLA-DR expression (83.7% versus 27.1%) and TLR4 expression on AMs (46.1% versus 9.9%) compared to patients without pneumonia. Already before surgery, the baseline of TLR2 expression on AM was significantly lower (27.7%) in patients who developed postoperative pneumonia.

Conclusions

As far as we know this is the first study that shows an early impairment of lung cellular immune response after cardiac surgery. These findings can help to understand the role of cell-mediated immunosuppression and its association to the development of postoperative pneumonia.     

Fetal circulation in left-sided congenital heart disease measured by cardiovascular magnetic resonance: a case–control study

Background

The distribution of blood flow in fetuses with congenital heart disease (CHD) is likely to influence fetal growth, organ development, and postnatal outcome, but has previously been difficult to study. We present the first measurements of the distribution of the fetal circulation in left-sided CHD made using phase contrast cardiac magnetic resonance (CMR).

Methods

Twenty-two fetuses with suspected left-sided CHD and twelve normal controls underwent fetal CMR and echocardiography at a mean of 35 weeks gestation (range 30–39 weeks).

Results

Fetuses with left-sided CHD had a mean combined ventricular output 19% lower than normal controls (p < 0.01). In fetuses with left-sided CHD with pulmonary venous obstruction, pulmonary blood flow was significantly lower than in those with left-sided CHD without pulmonary venous obstruction (p < 0.01). All three fetuses with pulmonary venous obstruction had pulmonary lymphangectasia by fetal CMR and postnatal histology. Fetuses with small but apex forming left ventricles with left ventricular outflow tract or aortic arch obstruction had reduced ascending aortic and foramen ovale flow compared with normals (p < 0.01). Fetuses with left-sided CHD had more variable superior vena caval flows than normal controls (p < 0.05). Six fetuses with CHD had brain weights at or below the 5^th centile for gestational age, while none of the fetuses in the normal control group had brain weights below the 25^th centile.

Conclusions

Measurement of the distribution of the fetal circulation in late gestation left-sided CHD is feasible with CMR. We demonstrated links between fetal blood flow distribution and postnatal course, and examined the relationship between fetal hemodynamics and lung and brain development. CMR enhances our understanding of pathophysiology of the fetal circulation and, with more experience, may help with the planning of perinatal management and fetal counselling.     

The distribution and prognosis of anomalous coronary arteries identified by cardiovascular magnetic resonance: 15?year experience from two tertiary centres

Background

Aberrant coronary arteries represent a diverse group of congenital disorders. Post-mortem studies reveal a high risk of exercise-related sudden cardiac death in those with an anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS) with an inter-arterial course. There is little documentation of lifetime history and long-term follow-up of patients with coronary artery anomalies.

Methods

Patients with anomalous coronary arteries undergoing cardiovascular magnetic resonance over a 15-year period were identified and classified by anatomy and course. Medical records were reviewed for major adverse cardiovascular events (MACE). Revascularisation or myocardial infarction counted only if occurring in the distribution of the anomalous artery.

Results

Consecutive patients with coronary artery anomalies were retrospectively identified (n = 172). Median follow-up time was 4.3 years (IQR 2.5–7.8, maximum 15.6). 116 patients had ACAOS of which 64 (55%) had an inter-arterial course (IAC) and 52 (45%) did not. During follow up 110 ACAOS patients were alive, 5 died and 1 lost to follow-up.ACAOS patients experienced 58 MACE events (5 cardiovascular deaths, 5 PCI, 24 CABG and 24 had myocardial infarction). 47 MACE events occurred in ACAOS with IAC and 11 in those without (p < 0.0001), the statistical difference driven by surgical revascularisation and myocardial infarction.

Conclusions

In life, patients with an anomalous coronary artery originating from the opposite sinus of Valsalva taking an IAC have higher rates of both myocardial infarction and surgical revascularisation during long-term follow up, compared to those without IAC.     

What role may symptoms play in the diagnosis of airflow limitation?: A study in an elderly population

Background

Chronic obstructive pulmonary disease (COPD) is an under-diagnosed condition. General practitioners meet and examine the patients in early stages of the disease, and symptoms represent the starting point of the diagnostic process.

Aim

To evaluate the diagnostic value of respiratory symptoms in the diagnosis of airflow limitation.

Methods

Spirometry was performed in a cross-sectional population-based study of 3954 subjects 60 years and older (54.5% women), who also filled in a questionnaire on symptoms.

Results

The prevalence of any airflow limitation was 15.5% and 20.8%, in women and men, respectively, whereas the corresponding prevalence of severe airflow limitation (FEV₁<50% predicted) was 3.4% and 4.9%. The positive predictive value of chronic cough with phlegm for any airflow limitation was 37.0% in women and 40.4% in men, and 17.3% and 14.2%, respectively, for severe airflow limitation. Wheezing was a symptom which persisted despite smoking cessation, whereas coughing was considerably less common in ex-smokers than in current smokers. Wheezing, dyspnoea on unhurried walking, dyspnoea on quick walking, and coughing with phlegm were independent predictors of any airflow limitation, OR 1.5, 1.8, 1.4, and 1.6 respectively. (The ORs for severe airflow limitation were 2.4, 2.4, 2.4, and 1.6 respectively.) To be an ex-smoker (OR 2.4) or a current smoker (OR 5.8) was of greater importance. In never- and ex-smokers the chance of having airflow limitation was almost doubled when having two or more, compared with one, of the three symptoms: wheezing, dyspnoea, and coughing with phlegm. Ex-smokers reporting two symptoms had a similar risk of airflow limitation to current smokers not reporting any symptoms.

Conclusion

Respiratory symptoms are valuable predictors of airflow limitation and should be emphasized when selecting patients for spirometry.     

Right ventricular hypertrophy after atrial switch operation: normal adaptation process or risk factor? A cardiac magnetic resonance study

Background

Systemic right ventricle (RV) hypertrophy and impaired function occur after atrial switch for dextro-transposition of the great arteries (d-TGA). Echocardiography is limited in its ability to assess the RV. We sought to evaluate systemic RV myocardial-mass index (MMI) and function after atrial switch and to analyse the role of hypertrophy for ventricular function with special consideration of the interventricular septal (IVS) movement.

Methods

Thirty-seven consecutive patients (median age 22.9?years) after atrial switch were studied using cardiac magnetic resonance imaging (1.5T Intera, Philips) with a dedicated 5-channel phased-array surface cardiac coil. Cine steady-state free-precession sequences were acquired to obtain myocardial masses and function. The systolic movement of the IVS was defined as positive when moving towards the centroid of the RV and was defined as non-positive otherwise. Patient parameters were compared to controls.

Results

The systemic RVs were significantly larger (p?<?0.001) than the left ventricles of the control group, systolic function was significantly impaired (p?<?0.001) and MMI including the IVS was comparable (p?=?n.s.). RV-MMI excluding the IVS and RV ejection fraction (EF) demonstrated a quadratic correlation (r?=?0.6, p?<?0.001), meaning that patients with RV-MMI ≤29?g/m² and >68?g/m² had a reduced level of systolic function. Positive septal movement improved RV function compared with non-positive septal movement (p?=?0.024).

Conclusions

There seems to be a range of beneficial RV hypertrophy after atrial switch in which a sufficient RV-EF can be expected. A positive septal movement, probably the result of hypertrophic septal RV fibres, improves RV function and might be regarded as a beneficial contraction pattern.     

The role of oncologists in multidisciplinary cancer teams in the UK: an untapped resource for team leadership?

Background and aims In the UK, cancer care is managed via multidisciplinary teams (MDT). Core members of these teams are typically surgeons, oncologists, radiologists, pathologists and clinical nurse specialists (with other health care professionals potentially present). Good teamwork, including team communication and leadership, has been shown to be a prerequisite for safe care delivery in other health care contexts, but cancer MDT team working processes are yet to be fully explored. This study aimed to assess the self‐perceived contribution of oncologists to MDTs, with emphasis on their potential role as team leaders. Methods Data were collected at the British Uro‐oncology Group 6th Annual Meeting (Sep 11–12 2009, York, UK). Respondents completed various items related to their perceived contribution to MDTs, aspects of current and potential MDT leadership, team decision making in these meetings, and also demographic information. Results Seventy‐seven oncologists attended the meeting, of whom 61 fully completed the survey (response rate 79%). Oncologists reported that their contribution to the MDT discussion carries equal weight to those of surgeons, radiologists and pathologists. Whereas 83% of respondents reported that MDT chairmanship could rotate, only 39% reported that it does in their own MDTs. More than 90% of respondents thought that oncologists (clinical or medical) could chair these meetings, but only 25% of them had ever chaired their own MDT. Conclusions Despite a high level of contribution to MDTs and the respect of their colleagues, oncologists are not taking leadership roles within MDTs at the level that they expect. This study raises the question of whether a re‐evaluation the leadership of MDTs is required with clinicians from a variety of specialities being given opportunities to develop skills necessary to lead cancer MDTs and improve team performance and ultimately cancer care.     

Role of computed tomography enterography/magnetic resonance enterography: is it in prime time?

Today, cross-sectional imaging modalities, such as computed tomography enterography (CTE) and magnetic resonance enterography (MRE), are particularly suited to evaluate small bowel diseases, especially Crohn's disease (CD). It is well known that CTE/MRE can provide excellent assessment of disease activity as well as the macroscopic features, extramural abnormalities, and complications of the small intestine in patients with CD. In general, CTE is considered as the first-line modality for the evaluation of suspected inflammatory bowel disease and for long-term assessment or follow-up of these patients. Because of the advantage of lack of radiation, MRE is being used more frequently, especially in children or young patients with CD.