T-tubule disease:Relationship between t-tubule organization and regional contractile performance in human dilated cardiomyopathy

Evidence from animal models suggest that t-tubule changes may play an important role in the contractile deficit associated with heart failure. However samples are usually taken at random with no regard as to regional variability present in failing hearts which leads to uncertainty in the relationship between contractile performance and possible t-tubule derangement. Regional contraction in human hearts was measured by tagged cine MRI and model fitting. At transplant, failing hearts were biopsy sampled in identified regions and immunocytochemistry was used to label t-tubules and sarcomeric z-lines. Computer image analysis was used to assess 5 different unbiased measures of t-tubule structure/organization. In regions of failing hearts that showed good contractile performance, t-tubule organization was similar to that seen in normal hearts, with worsening structure correlating with the loss of regional contractile performance. Statistical analysis showed that t-tubule direction was most highly correlated with local contractile performance, followed by the amplitude of the sarcomeric peak in the Fourier transform of the t-tubule image. Other area based measures were less well correlated. We conclude that regional contractile performance in failing human hearts is strongly correlated with the local t-tubule organization. Cluster tree analysis with a functional definition of failing contraction strength allowed a pathological definition of ‘t-tubule disease’. The regional variability in contractile performance and cellular structure is a confounding issue for analysis of samples taken from failing human hearts, although this may be overcome with regional analysis by using tagged cMRI and biopsy mapping

Clinical outcome 10 years after attempted percutaneous transluminal coronary angioplasty in 856 patients.

Abstract OBJECTIVES: This study reports the 10-year outcome of 856 consecutive patients who underwent attempted coronary angioplasty at the Thoraxcenter during the years 1980 to 1985. BACKGROUND: Coronary balloon angioplasty was first performed in 1977, and this procedure was introduced into clinical practice at the Thoraxcenter in 1980. Although advances have been made, extending our knowledge of the long-term outcome in terms of survival and major cardiac events remains of interest and a valuable guide in the treatment of patients with coronary artery disease. METHODS: Details of survival, cardiac events, symptoms and medication were retrospectively obtained from the Dutch civil registry, medical records or by letter or telephone or from the patient's physician and entered into a dedicated data base. Patient survival curves were constructed, and factors influencing survival and cardiac events were identified. RESULTS: The procedural clinical success rate was 82%. Follow-up information was obtained in 837 patients (97.8%). Six hundred forty-one patients (77%) were alive, of whom 334 (53%) were symptom free, and 254 (40%) were taking no antianginal medication. The overall 5- and 10-year survival rates were 90% (95% confidence interval [CI] 87.6% to 92.4%) and 78% (95% CI 75.0% to 81.0%), respectively, and the respective freedom from significant cardiac events (death, myocardial infarction, coronary artery bypass surgery and repeat angioplasty) was 57% (95% CI 53.4% to 60.6%) and 36% (95% CI 32.4% to 39.6%). Factors that were found to adversely influence 10-year survival were age > or = 60 years (> or = 60 years [67%], 50 to 59 years [82%], or = 50% [80%]) and a history of previous myocardial infarction (previous myocardial infarction [72%], no previous infarction [83%]). These factors were also found to be independent predictors of death during the follow-up period by a multivariate stepwise logistic regression analysis. Other factors tested, with no influence on survival, were gender, procedural success and stability of angina at the time of intervention. CONCLUSIONS: The long-term prognosis of patients after coronary angioplasty is good, particularly in those <60 years old with single-vessel disease and normal left ventricular function. The majority of patients are likely to experience a further cardiac event in the 10 years after their first angioplasty procedure

Mapping system for coregistration of cardiac MRI and ex vivo tissue sampling

To design a method suitable for obtaining tissue samples from regions of different function as ascertained by magnetic resonance imaging (MRI)

Highly variable contractile performance correlates with myocyte content in trabeculae from failing human hearts

Heart failure (HF) is defined by compromised contractile function and is associated with changes in excitation-contraction (EC) coupling and cardiomyocyte organisation. Tissue level changes often include fibrosis, while changes within cardiomyocytes often affect structures critical to EC coupling, including the ryanodine receptor (RyR), the associated protein junctophilin-2 (JPH2) and the transverse tubular system architecture. Using a novel approach, we aimed to directly correlate the influence of structural alterations with force development in ventricular trabeculae from failing human hearts. Trabeculae were excised from explanted human hearts in end-stage failure and immediately subjected to force measurements. Following functional experiments, each trabecula was fixed, sectioned and immuno-stained for structural investigations. Peak stress was highly variable between trabeculae from both within and between failing hearts and was strongly correlated with the cross-sectional area occupied by myocytes (MCSA), rather than total trabecula cross-sectional area. At the cellular level, myocytes exhibited extensive microtubule densification which was linked via JPH2 to time-to-peak stress. Trabeculae fractional MCSA variability was much higher than that in adjacent free wall samples. Together, these findings identify several structural parameters implicated in functional impairment in human HF and highlight the structural variability of ventricular trabeculae which should be considered when interpreting functional data

Diagnosis of myocardial infarction and prognostic utility of high-sensitivity troponin T after isolated aortic valve replacement

Background: The Universal Definition for type 5 myocardial infarction (MI) applies to coronary artery bypass grafting (CABG), while MIs for other cardiac surgery are not specifically defined. We assessed whether elevated high-sensitivity troponin (hs-TnT), with electrocardiogram (ECG) changes and/or new wall motion abnormalities on echocardiography as defined by the Universal Definition, predicted mortality and/or morbidity after aortic valve replacement (AVR) (n = 219). Methods: Consecutive patients with isolated AVR performed during July 2010–December 2012 and followed-up for 2.3 ± 0.8 years. Hs-TnT was measured 12–24 h post-operatively. ECG and/or echocardiographic changes with hs-TnT >140 ng/L (10 times 99th percentile upper reference limit and >500 ng/L (10 times the coefficient of variation of 10% for 4th generation troponin T applied to hs-TnT) were pre-specified as the criteria for MI diagnosis. Results: There were 9.1% (20) and 3.7% (8) patients with ECG and/or echocardiographic changes and hs-TnT > 140 ng/L and hs-TnT > 500 ng/L respectively. Neither criterion was independently associated with 30-day mortality (2.7%). Hs-TnT > 500 ng/L and ECG and/or echocardiographic changes was independently associated with mortality (5.5%) during follow-up, hazards ratio 5.23, 95% confidence interval 1.09–25.2, p = 0.039. Hs-TnT per 100 ng/L as a continuous parameter was independently associated with 30-day mortality, mortality during follow-up and composite morbidity. Conclusion: The Universal Definition of MI, using 10 times the URL for the 4th generation troponin T and 35 times the URL for hs-TnT with a cutpoint of > 500 ng/L with ECG and/or echocardiographic changes, independently predicted median term mortality after AVR. Hs-TnT as a continuous parameter was independently associated with mortality at both time points and morbidity

Origin of plasma cell-free DNA after solid organ transplantation

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