Background-Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessment is an important factor in determining medical treatment and lung transplantation. Whether cardiopulmonary exercise testing data predict survival has not been reported previously. Methods and Results-We studied 86 patients with PPH (58 female, age 46Ϯ2 years, median NYHA class III) between 1996 and 2001 who were followed up in a tertiary referral center. Right heart catheterization was performed and serum uric acid levels were measured in all patients. Seventy patients were able to undergo exercise testing. At the start of the study, the average pulmonary artery pressure was 60Ϯ2 mm Hg, average pulmonary vascular resistance was 1664Ϯ81 dyne · s · cm

T cells are crucial for the control of cytomegalovirus (CMV) in infected individuals. Although CMV-specific T cells can be quantified by various methods, clear correlates of protection from CMV disease have not been defined. However, responses to the pp65 protein are believed to play an important role. Here, the proportions of interferon γ–producing T cells following ex vivo activation with pools of overlapping peptides representing the pp65 and immediate early (IE)-1 proteins were determined at multiple time points and related to the development of CMV disease in 27 heart and lung transplant recipients. Frequencies of IE-1–specific CD8 T cells above 0.2 and 0.4% at day 0 and 2 wk, respectively, or 0.4% at any time during the first months discriminated patients who did not develop CMV disease from patients at risk, 50–60% of whom developed CMV disease. No similar distinction between risk groups was possible based on pp65-specific CD8 or CD4 T cell responses. Remarkably, CMV disease developed exclusively in patients with a dominant pp65-specific CD8 T cell response. In conclusion, high frequencies of IE-1 but not pp65-specific CD8 T cells correlate with protection from CMV disease. These results have important implications for monitoring T cell responses, adoptive cell therapy, and vaccine design.

This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM.

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Echocardiographic strain and strain-rate imaging (deformation imaging) is a new non-invasive method for assessment of myocardial function. Due to its ability to differentiate between active and passive movement of myocardial segments, to quantify intraventricular dyssynchrony and to evaluate components of myocardial function, such as longitudinal myocardial shortening, that are not visually assessable, it allows comprehensive assessment of myocardial function and the spectrum of potential clinical applications is very wide. The high sensitivity of both tissue Doppler imaging (TDI) derived and two dimensional (2D) speckle tracking derived myocardial deformation (strain and strain rate) data for the early detection of myocardial dysfunction recommend these new non-invasive diagnostic methods for extensive clinical use. In addition to early detection and quantification of myocardial dysfunction of different etiologies, assessment of myocardial viability, detection of acute allograft rejection and early detection of allograft vasculopathy after heart transplantation, strain and strain rate data are helpful for therapeutic decisions and also useful for follow-up evaluations of therapeutic results in cardiology and cardiac surgery. Strain and strain rate data also provide valuable prognostic information, especially prediction of future reverse remodelling after left ventricular restoration surgery or after cardiac resynchronization therapy and prediction of short and median-term outcome without transplantation or ventricular assist device implantation of patients referred for heart transplantation.The Review explains the fundamental concepts of deformation imaging, describes in a comparative manner the two major deformation imaging methods (TDI-derived and speckle tracking 2D-strain derived) and discusses the clinical applicability of these new echocardiographic tools, which recently have become a subject of great interest for clinicians.

Abstract-Despite its importance for the regulation of heart function, little is known about the isoform expression of the multifunctional Ca 2ϩ /calmodulin-dependent protein kinase (CaMKII) in human myocardium. In this study, we investigated the spectrum of CaMKII isoforms ␦ 2 , ␦ 3 , ␦ 4 , ␦ 8 , and ␦ 9 in human striated muscle tissue. Isoform ␦ 3 is characteristically expressed in cardiac muscle. In skeletal muscle, specific expression of a new isoform termed ␦ 11 is demonstrated. Complete sequencing of human ␦ 2 cDNA, representing all common features of the investigated CaMKII subclass, revealed its high homology to the corresponding rat cDNA. Comparative semiquantitative reverse transcription-polymerase chain reaction analyses from left ventricular tissues of normal hearts and from patients suffering from dilated cardiomyopathy showed a significant increase in transcript levels of isoform ␦ 3 relative to the expression of glyceraldehyde-3-phosphate dehydrogenase in diseased hearts (101.6Ϯ11.0% versus 64.9Ϯ9.9% in the nonfailing group; PϽ0.05, nϭ6). Transcript levels of the other investigated cardiac CaMKII isoforms remained unchanged. At the protein level, by using a subclass-specific antibody, we observed a similar increase of a ␦-CaMKII-specific signal (7.2Ϯ1.0 versus 3.8Ϯ0.7 optical density units in the nonfailing group; PϽ0.05, nϭ4 through 6). The diseased state of the failing hearts was confirmed by a significant increase in transcript levels for atrial natriuretic peptide (292.9Ϯ76.4% versus 40.1Ϯ3.2% in the nonfailing group; PϽ0.05, nϭ3 through 6). Our data characterize for the first time the ␦-CaMKII isoform expression pattern in human hearts and demonstrate changes in this expression pattern in heart failure. (Circ Res. 1999;84:713-721.)

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AimsUnloading-promoted reversal of heart failure (HF) allows long-term transplant-free outcome after ventricular assist device (VAD) removal. However, because few patients with chronic cardiomyopathy (CCM) were weaned from VADs (the majority only recently), the reliability of criteria used for weaning decisions to predict long-term post-weaning success is barely known. After 15 years of weaning experience, we assessed this issue.Methods and resultsIn 47 patients with CCM as the underlying cause for HF, who were part of a total of 90 patients weaned from bridge-to-transplant-designed VADs since 1995, we analysed data on cardiac morphology and function collected before VAD implantation, echocardiographic parameters recorded during ‘off-pump’ trials, duration of HF before implantation, and stability of recovery before and early after VAD removal. Post-weaning 5 year freedom from HF recurrence reached 66%. Only five patients (10.6%) died due to HF recurrence or weaning-related complications. Pre-explantation off-pump left ventricular ejection fraction (LVEF) of ≥50 and ≥45% revealed predictive values for cardiac stability lasting ≥5 years after VAD removal of 91.7 and 79.1%, respectively. With each unit of LVEF reduction, the risk of HF recurrence became 1.5 times higher. The predictive value of LVEF ≥45% also became >90% if additional parameters like pre-explantation LV size and geometry, stability of unloading-induced cardiac improvement before VAD removal, and HF duration before VAD implantation were also considered. Definite cut-off values for certain parameters (including tissue-Doppler-derived LV wall motion velocity) allowed formulation of weaning criteria with high predictability for post-weaning stability, also in patients with incomplete cardiac recovery.ConclusionsVentricular assist device removal in CCM patients is feasible and can be successful even after incomplete cardiac recovery. Parameters of pre-explantation cardiac function, LV size and geometry, their stability during final off-pump trials, and HF duration allow detection of patients with the potential to remain stable for >5 post-weaning years.