High-Sensitivity Troponin T and Soluble Form of AXL as Long-Term Prognostic Biomarkers after Heart Transplantation.

ANTECEDENTS: Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. AIM: Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. METHODS: 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction < 50%, or heart failure not due to an acute rejection. RESULTS: 51 patients (53%) presented CAV at evaluation; 21 of them had CV events. Hs-cTnT (56 ± 45 versus 20 ± 18 ng/L; p = 0.04) and sAXL concentrations (98 ± 51 versus 26 ± 26 ng/L; p = 0.01) were significantly higher in patients with CV events. Hs-cTnT (HR 1.03; 95% CI 1.015-1.042, p = 0.0001) and sAXL (HR 1.01; 95% CI 1.001-1.019, p = 0.02) were independent predictors of CV events. A hs-cTnT concentration < 21 ng/L, detected by AUC ROC, predicted the absence of CV events with a predictive value of 91%; sAXL did not add more predictive value to hs-cTnT. Survival free of CV events was 92% in patients with hs-cTnT < 21 ng/L and 57% in those with hs-cTnT > 21 ng/L (p < 0.001). CONCLUSION: Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes.

Tricuspid valve replacement with mechanical prostheses: Short and long-term outcomes.

BACKGROUND AND AIM: Tricuspid valve replacement has been associated with high mortality and poor long-term outcomes. We report the preoperative risk factors associated with short and long-term outcomes following tricuspid valve replacement with mechanical prostheses. METHODS: In 62 patients who underwent mechanical tricuspid valve replacement, clinical, laboratory, and echocardiographic findings were analyzed using both univariate and multivariate analyses to describe operative and long-term mortality. RESULTS: In our population (mean age 59 ± 9.7 years, 82.3% female), most common causes of tricuspid valve disease were rheumatic fever (69.4%) and functional regurgitation (19.4%). Operative and long-term mortality were 17.7 and 33.9%, respectively. Age, diabetes mellitus, and coronary artery disease were independently associated with increased long-term mortality. New York Heart Association (NYHA) class and right heart failure symptoms significantly improved during follow-up. CONCLUSIONS: In this series of mechanical tricuspid valve replacements in patients with predominately rheumatic heart disease, operative and long-term mortality were increased; however, survivors had significant improvement in their NYHA class and freedom from right heart failure symptoms. Three preoperative factors (age, diabetes mellitus, and coronary artery disease) were independently associated with long-term mortality.

Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes.

AIMS: Ageing-related cardiac disorders such as heart failure and atrial fibrillation often present with intracellular calcium homeostasis dysfunction. However, knowledge of the intrinsic effects of ageing on cellular calcium handling in the human heart is sparse. Therefore, this study aimed to analyse how ageing affects key mechanisms that regulate intracellular calcium in human atrial myocytes. METHODS AND RESULTS: Whole membrane currents and intracellular calcium transients were measured in isolated human right atrial myocytes from 80 patients with normal left atrial dimensions and no history of atrial fibrillation. Patients were categorized as young (<55 years, n = 21), middle aged (55-74 years, n = 42), and old (≥75 years, n = 17). Protein levels were determined by western blot. Ageing was associated with the following electrophysiological changes: (i) a 3.2-fold decrease in the calcium transient (P < 0.01); (ii) reduction of the L-type calcium current (ICa) amplitude (2.4 ± 0.3 pA/pF vs. 1.4 ± 0.2 pA/pF, P < 0.01); (iii) lower levels of L-type calcium channel alpha-subunit (P < 0.05); (iv) lower rates of both fast (14.5 ± 0.9 ms vs. 20.9 ± 1.9, P < 0.01) and slow (73 ± 3 vs. 120 ± 12 ms, P < 0.001) ICa inactivation; and (v) a decrease in the sarcoplasmic reticulum calcium content (10.1 ± 0.8 vs. 6.4 ± 0.6 amol/pF, P < 0.005) associated with a significant decrease in both SERCA2 (P < 0.05) and calsequestrin-2 (P < 0.05) protein levels. In contrast, ageing did not affect spontaneous sarcoplasmic reticulum calcium release. CONCLUSION: Ageing is associated with depression of SR calcium content, L-type calcium current, and calcium transient amplitude that may favour a progressive decline in right atrial contractile function with age.

The Sorin Freedom SOLO stentless aortic valve: easier implantation technique with potentially less risk of complications.

Aortic valve replacement by bioprosthesis is increasingly being used. Among these, stentless bioprosthesis is becoming a valid choice due to its potential hemodynamic improvement. The Sorin Freedom SOLO stentless aortic valve (FS) (Sorin Biomedica Cardio, Saluggia, Italy) is widely used, with initial and midterm promising results. It is designed to be deployed in a straightforward manner in the supraannular position with a single running suture due to its reproducible implantation technique. Few specific valve-related complications, such as transient thrombocytopenia or rare thrombotic events, are known. Our experience, after the implantation of 33 Freedom SOLO, suggests that using the classical implantation technique, the noncoronary sinus adopts a conformation that increases the difficulty of the implant. Besides, it could also be distorted increasing the risk of periprosthetic leakage and hypothetically becoming the origin of thrombus. We present an easy and safe variation in the implantation technique of the FS that decreases the technical difficulty of the implantation, reduces the risk of periprosthetic leakage, and may additionally reduce the risk of thrombosis.

Ruling out coronary artery disease with noninvasive coronary multidetector CT angiography before noncoronary cardiovascular surgery.

PURPOSE: To assess the usefulness of preoperative coronary computed tomographic (CT) angiography in the detection of coronary artery disease (CAD) in nonselected patients scheduled to undergo noncoronary cardiovascular surgery to avoid unnecessary invasive coronary angiography (ICA). MATERIALS AND METHODS: The institutional review board approved the study protocol; informed consent was given. This prospective study involved 161 consecutive patients who underwent coronary calcium scoring and coronary CT angiography before undergoing noncoronary cardiovascular surgery. Seven patients were excluded because of contraindications to CT angiography. The major indication of noncoronary cardiovascular surgery was valvular heart disease (121 patients). Follow-up was performed at a median of 20 months to define ischemic events described as acute coronary syndrome or death secondary to acute coronary syndrome, arrhythmias, or cardiac failure. Multivariate analysis was performed to determine predictors of nondiagnostic coronary CT angiography. Kaplan-Meier analysis was performed to evaluate outcome at follow-up. RESULTS: Twenty-one patients did not undergo surgery, which left 133 patients as the study group. Atrial fibrillation was present in 45 of 133 patients. The interquartile range of the Agatston coronary calcium score was 0-471. Coronary CT angiography was diagnostic in 108 of 133 patients. Of these, 93 of 108 had no significant CAD (≤ 50% stenosis), and noncoronary cardiovascular surgery was performed in them without preoperative ICA. No patients in this group had postoperative ischemic events at follow-up. Coronary CT angiography was nondiagnostic in 25 of 133 patients who were referred for preoperative ICA. Multivariate analysis showed Agatston score to be the only independent predictor of nondiagnostic coronary CT angiography (odds ratio = 1.002; 95% confidence interval: 1.001, 1.003; P = .001). The best Agatston score cutoff for diagnostic coronary CT angiography was 579. CONCLUSION: In nonselected patients scheduled to undergo noncoronary cardiovascular surgery, preoperative coronary CT angiography was diagnostic in 81% of cases. Preoperative ICA could be safely avoided in patients without significant CAD by using coronary CT angiography. The Agatston score, but not the presence of atrial fibrillation, was an independent predictor of nondiagnostic coronary CT angiography. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100384/-/DC1.

Changes in myocardial electrical impedance in human heart graft rejection.

BACKGROUND: Monitoring of post-transplant heart rejection is currently based on endomyocardial biopsy analysis. This study aimed to assess the effects of heart graft rejection on myocardial electrical impedance. METHODS AND RESULTS: Twenty-nine cardiac transplant patients and 9 controls underwent measurement of myocardial electrical impedance using a specifically designed amplifying system. The module and phase angle of myocardial impedance were measured. Histopathological rejection grading was performed according to ISHLT classification. Fifty impedance tests were performed in transplanted patients. Myocardial impedance (Z) was higher in controls than in transplanted patients (p<0.001) and followed a progressive decline at increasing current frequencies (p<0.001). Likewise, the phase angle of impedance in controls ranged from positive values at low frequencies to negative values at higher frequencies (from 2.5+/-0.9 degrees at 10 kHz to -3.8+/-2.1 degrees at 300 kHz, p<0.001). Rejection was associated with a significant decrease in myocardial impedance (Z) (15+/-6.6 Omega in grade 0, 13+/-6.0 Omega in grade 1A, and 3.3+/-0.9 Omega in grade 3A at 10 kHz, p<0.003). CONCLUSIONS: Mild degrees of cardiac graft rejection are associated with significant changes in myocardial electrical impedance in transplant patients. Further clinical investigation is warranted to assess the potential of cardiac impedance to detect heart graft rejection.

Host cell-derived cardiomyocytes in sex-mismatch cardiac allografts.

BACKGROUND: Mesenchymal precursor cells are able to respond to tissue signals and differentiate into a phenotype characteristic of mature cells of that tissue. We sought to investigate whether adult human cardiomyocytes can be derived from recipient precursor cells in sex-mismatched cardiac allografts. METHODS: We studied four male patients who received hearts from female donors, and four female patients who received an allograft from a male donor. Four sex-matched transplant patients, two of each sex served as controls. Combined fluorescence in situ hybridization with probes specific for X- and Y-chromosomes and immunohistochemistry with alpha-actin was used to identify cardiac muscle cells 4 and 12 months after transplantation. Slides were examined with a fluorescence microscope to detect the presence of male cells with one X and one Y signal in the nucleus, and female cells containing two X signals. RESULTS: Mature cardiomyocytes from the host (1-2%) were found in five endomyocardial biopsy specimens at 4 months, and in three specimens at 12 months. In addition, recipient cells negative for cytoplasmic alpha-actin were also identified (1-21% per slide). The number of infiltrating recipient cells was not associated with the degree of rejection of the sample or with the number of prior rejection episodes. Echocardiographic evaluation showed no improvement in cardiac performance in hearts from patients with more than 10% chimeric recipient cells. CONCLUSIONS: Our data confirm the existence of mature cardiomyocytes derived from host cells, likely mesenchymal precursors, in the adult cardiac allograft in vivo.