Caliskan, K.

Primary electrical disorder or primary cardiomyopathy?: A case with a unique association of noncompaction cardiomyopathy and cathecolaminergic polymorphic ventricular tachycardia caused by ryanodine receptor mutation (Article)

2013-03-12T00:00:00Z

Clinical features of Noncompaction Cardiomyopathy (Doctoral Thesis)

2012-09-06T00:00:00Z

Noncompaction cardiomyopathy (NCCM) is recognized as a separate disease entity since the first report in 1984 of a rare case with persistent myocardial sinusoids and a series of 8 pediatric and adolescent patients in 1990 with increased trabeculation of the left ventricular endocardium. Given the cumulative evidence since then, NCCM is considered as a primary, predominantly genetic disorder of the myocardium. The classic clinical presentation includes severe heart failure, malignant ventricular arrhythmias, thrombo-embolic events and sudden cardiac death. But the complete spectrum comprises also asymptomatic to minor cardiac complaints like atypical chest pain and nonspecific palpitations. The noncompacted myocardium is characterized by an excessively prominent trabecular meshwork and deep intertrabecular recesses, as seen early in human embryogenesis. Therefore, the primary patho-physiological hypothesis is that incomplete compaction of the loose myocardial meshwork during gestation results in a noncompacted, heart, prone to heart failure, arrhythmias and intracardiac thrombus formation. The diagnostic criteria proposed by Jenni et al. include abnormally thickened ventricular walls with a two-layered structure, consisting of thickened, noncompacted (NC) endocardial myocardium and a thin compacted (C) epicardial myocardium (maximal end-systolic ratio NC/C 2 at parasternal short axis view). The diagnosis is established by imaging of the ventricular walls and cavities, classically by two-dimensional transthoracic echocardiography with color Doppler flow. The abnormal structures of NCCM could be identified as deep intertrabecular recesses with color Doppler flow as well as regional hypokinesia. Other imaging modalities like left ventricular (LV) angiography, computed tomography, contrast echocardiography and maghese recesses. Increased awareness of this disease entity made us recognize more and more cases of NCCM, especially with help of modern maging modalities like contrast echocardiography and MRI allowing better visualization the left ventricular cavity. However, in daily clinical practice, many questions about several clinical aspects remained open, because the available literature consisted of several case reports and small case series only.

Normal left ventricular twist in patients with non-compaction cardiomyopathy, or in normal subjects with hypertrabeculation? (Article)

2012-09-01T00:00:00Z

Long-term follow-up of prophylactic implantable cardioverter-defibrillator- only therapy: Comparison of ischemic and nonischemic heart disease (Article)

2011-12-01T00:00:00Z

Background: The benefits of primary prophylactic implantable cardioverter-defibrillators (ICDs) are actually debated, as some drawbacks become more apparent and as the natural history of cardiac disease seems to improve. Therefore, contemporary follow-up data of non-trial populations treated according to current guidelines remain necessary. The aim of this study was to evaluate mortality and the occurrence of ICD interventions in patients with coronary artery disease (CAD) and dilated cardiomyopathy (DCM) who received in the recent era a primary prophylactic ICD without resynchronization therapy. Hypothesis: Survival and event-free rates from appropriate ICD therapy are different between ischemic and nonischemic ICD patients. Methods: Prospective cohort study of 427 consecutive primary prevention ICD patients with ischemic or nonischemic heart disease, excluding patients with resynchronization. Results: Ischemic heart disease was present in 290 patients (68%), nonischemic heart disease in 137 patients (32%). During a median follow-up of 31 months (interquartile range [IQR] 15-45 months), 30 patients (7%) died. Mortality was not different in both disease categories. The incidence of appropriate ICD interventions was similar in CAD and DCM (23% vs 21%). Appropriate ICD intervention occurred more frequently in patients with atrial fibrillation (29% vs 19%). Inappropriate ICD intervention occurred in 11% of patients. Conclusions: The clinical course of ischemic and nonischemic heart disease patients treated with a primary prophylactic ICD is similar with respect to mortality and to appropriate and inappropriate ICD interventions, in spite of a younger age at baseline of the DCM patients.

Indications and outcome of implantable cardioverter-defibrillators for primary and secondary prophylaxis in patients with noncompaction cardiomyopathy (Article)

2011-08-01T00:00:00Z

Prophylactic ICDs for Noncompaction Cardiomyopathy. Background: Noncompaction cardiomyopathy (NCCM) is a rare, primary cardiomyopathy, with initial presentation of heart failure, emboli, or arrhythmias, including sudden cardiac death. Implantable cardioverter-defibrillators (ICDs) are frequently used for primary and secondary prevention in different cardiomyopathy patients, but data about ICD in NCCM are scarce. The aim of this study was, therefore, to investigate ICD indications and outcomes in NCCM patients. Methods and Results: We collected prospective data from our NCCM cohort (n = 77 pts, mean age: 40 ± 14 years). ICD was implanted in 44 (57%) patients with NCCM according to the current ICD guidelines for nonischemic cardiomyopathies: in 12 for secondary prevention (7 × ventricular fibrillation, 5 × sustained ventricular tachycardia [VT]) and in 32 patients for primary prevention (heart failure/severe LV dysfunction). During a mean follow-up of 33 ± 24 months, 8 patients presented with appropriate ICD shocks due to sustained VT after median 6.1 [1-16] months. This included 4 of 32 (13%) patients in the primary prevention group and 4 of 12 (33%) in the secondary prevention group (P = 0.04). 9 patients presented with inappropriate ICD therapy: 6 (19%) in the primary and 3 (25%) in the secondary prevention group, at a median follow-up of 4 (2-23) months. Conclusions: In our cohort of NCCM patients, an ICD was frequently implanted for primary or secondary prevention of sudden cardiac death. At follow-up, frequent appropriate ICD therapy was observed in both groups, supporting the application of current ICD guidelines for primary and secondary prevention of sudden cardiac death in NCCM.

Diagnostic Value of Rigid Body Rotation in Noncompaction Cardiomyopathy (Article)

2011-05-01T00:00:00Z

Background: The diagnosis of noncompaction cardiomyopathy (NCCM) remains subject to controversy. Because NCCM is probably caused by an intrauterine arrest of the myocardial fiber compaction during embryogenesis, it may be anticipated that the myocardial fiber helices, normally causing left ventricular (LV) twist, will also not develop properly. The resultant LV rigid body rotation (RBR) may strengthen the diagnosis of NCCM. The purpose of the current study was to explore the diagnostic value of RBR in a large group of patients with prominent trabeculations. Methods: The study comprised 15 patients with dilated cardiomyopathy, 52 healthy subjects, and 52 patients with prominent trabeculations, of whom a clinical expert in NCCM defined 34 as having NCCM. LV rotation patterns were determined by speckle-tracking echocardiography and defined as follows: pattern 1A, completely normal rotation (initial counterclockwise basal and clockwise apical rotation, followed by end-systolic clockwise basal and counterclockwise apical rotation); pattern 1B, partly normal rotation (normal end-systolic rotation but absence of initial rotation in the other direction); and pattern 2, RBR (rotation at the basal and apical level predominantly in the same direction). Results: The majority of normal subjects had LV rotation pattern 1A (98%), whereas the 18 subjects with hypertrabeculation not fulfilling diagnostic criteria for NCCM predominantly had pattern 1B (71%), and the 34 patients with NCCM predominantly had pattern 2 (88%). None of the patients with dilated cardiomyopathy showed RBR. Sensitivity and specificity of RBR for differentiating NCCM from "hypertrabeculation" were 88% and 78%, respectively. Conclusions: RBR is an objective, quantitative, and reproducible functional criterion with good predictive value for the diagnosis of NCCM as determined by expert opinion.

Paradoxical effects of interatrial conduction delay in a hypertrophic cardiomyopathy patient in the long-term: Time is a great healer (Article)

2011-05-01T00:00:00Z

Paradoxical Effects of Interatrial Conduction Delay. We present a unique case where early proarrhythmic and late antiarrhythmic characteristics of interatrial conduction delay were observed during the long-term progression of HCM. Occurrence of AT constantly increased as the interatrial conduction delay became more prominent, while the P-wave width in sinus rhythm and the AT cycle length both showed an instantaneous increase in parallel. As the interatrial delay reached a critical point, the right and left atrial P-wave became virtually separated, as demonstrated by the findings of ECGs and echocardiography. This phenomenon resulted in the complete cessation of tachycardias. (J Cardiovasc Electrophysiol, Vol. 22, pp. 587-589 May 2011)

Bradycardiomyopathy: The case for a causative relationship between severe sinus bradycardia and heart failure (Article)

2010-07-01T00:00:00Z

Bradycardiomyopathy. A 28-year-old man presented with progressive fatigue. Physical examination and ECG revealed severe sinus bradycardia. Echocardiography showed features of noncompaction cardiomyopathy and moderate aortic valve regurgitation. We hypothesized that the chronic volume overload exaggerated by prolonged diastole due to the bradycardia resulted in heart failure and noncompaction cardiomyopathy look-alike features. After implantation of an AAI pacemaker, his symptoms and signs of cardiomyopathy were fully recovered.

The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy (Article)

2010-06-01T00:00:00Z

Background-Left ventricular (LV) noncompaction(LVNC) is a distinct cardiomyopathy featuring a thickened bilayered LV wall consisting of a thick endocardial layer with prominent intertrabecular recesses with a thin, compact epicardial layer. Similar to hypertrophic and dilated cardiomyopathy, LVNC is genetically heterogeneous and was recently associated with mutations in sarcomere genes. To contribute to the genetic classification for LVNC, a systematic cardiological family study was performed in a cohort of 58 consecutively diagnosed and molecularly screened patients with isolated LVNC (49 adults and 9 children). Methods and Results-Combined molecular testing and cardiological family screening revealed that 67% of LVNC is genetic. Cardiological screening with electrocardiography and echocardiography of 194 relatives from 50 unrelated LVNC probands revealed familial cardiomyopathy in 32 families (64%), including LVNC, hypertrophic cardiomyopathy, and dilated cardiomyopathy. Sixty-three percent of the relatives newly diagnosed with cardiomyopathy were asymptomatic. Of 17 asymptomatic relatives with a mutation, 9 had noncompaction cardiomyopathy. In 8 carriers, nonpenetrance was observed. This may explain that 44% (14 of 32) of familial disease remained undetected by ascertainment of family history before cardiological family screening. The molecular screening of 17 genes identified mutations in 11 genes in 41% (23 of 56) tested probands, 35% (17 of 48) adults and 6 of 8 children. In 18 families, single mutations were transmitted in an autosomal dominant mode. Two adults and 2 children were compound or double heterozygous for 2 different mutations. One adult proband had 3 mutations. In 50% (16 of 32) of familial LVNC, the genetic defect remained inconclusive. Conclusion-LVNC is predominantly a genetic cardiomyopathy with variable presentation ranging from asymptomatic to severe. Accordingly, the diagnosis of LVNC requires genetic counseling, DNA diagnostics, and cardiological family screening.

Double intra-atrial connections in a patient late after orthotopic heart transplantation (Article)

2010-06-01T00:00:00Z

Atrial tachycardias occurring late after orthotopic heart transplantation are frequently caused by an ongoing atrial tachycardia in the recipient remnant atrium that is associated with intra-atrial muscle band connections between the 2 atrial compartments. The standard approach for most centers that treat these patients is to identify and disconnect these intra-atrial connections. We present a patient where double intra-atrial connections were capable of different degrees of stimulus propagation from the recipient remnant atrium to the donor atrial compartment. After the ablation of both intra-atrial connections, we also ablated the index arrhythmia in the recipient remnant atrium. This case presentation draws attention to the possibility of the presence of multiple intra-atrial connections.

Empty handed: A call for an international registry of risk stratification to reduce the 'sudden-ness' of death in patients with non-compaction cardiomyopathy (Article)

2009-09-01T00:00:00Z

Dose-dependent benefit of nitroglycerin on microcirculation of patients with severe heart failure (Article)

2009-07-29T00:00:00Z

Introduction: Microcirculatory abnormalities are frequently observed in patients with severe heart failure and correlate to worse outcomes. We tested the hypothesis that nitroglycerin dose-dependently improves perfusion in severe heart failure and that this could be monitored by measuring central-peripheral temperature gradient and with Sidestream Dark Field imaging of the sublingual mucosa. Methods: A dose-response study was performed in 17 patients with cardiogenic shock (n = 9) or end-stage chronic heart failure (n = 8) admitted to Erasmus University Medical Center. We did hemodynamic measurements at baseline and during increasing infusion rates of nitroglycerin (up to a maximum dose of 133 μg min-1). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). Results: Nitroglycerin dose-dependently decreased mean arterial pressure (p < 0.001) and cardiac filling pressures (both central venous pressure (CVP) and pulmonary capillary wedge pressure: p < 0.001). It increased cardiac index (p = 0.01). Nitroglycerin decreased delta-T (p < 0.001) and increased sublingual PCD (p < 0.001). Significant changes in delta-T and PCD occurred earlier, i.e., at a lower doses of NTG, than changes in global hemodynamics. Macrohemodynamic and microcirculatory responses to nitroglycerin infusion were consistent in patients with either cardiogenic shock or end-stage chronic heart failure. Changes in microcirculatory parameters occurred independently of changes in cardiac index. Conclusions: Nitroglycerin dose-dependently increases tissue perfusion in patients with severe heart failure, as observed by a decrease in central-peripheral temperature gradient and an increase in sublingual perfused capillary density.

Reduced regional systolic function is not confined to the noncompacted segments in noncompaction cardiomyopathy (Article)

2009-05-29T00:00:00Z

Background: Isolated ventricular noncompaction (IVNC) is a relatively rare genetic primary cardiomyopathy. The aim of the present study was to investigate with regional real-time three-dimensional echocardiographic analysis whether there is a difference between the contribution of noncompacted and compacted left ventricular (LV) segments to global LV dysfunction in patients with IVNC. Methods: The study comprised 289 segments of 17 patients with stringent diagnostic criteria for IVNC. Their results were compared to 153 segments of 9 control subjects. The systolic performance of compacted and noncompacted LV segments was assessed using the wall motion score during 2D echocardiography. The 3D images were acquired with a RT3DE system with X4 matrix-array transducer and were used for the regional volume measurements. Results: Wall motion score index was markedly abnormal in the compacted LV segments of IVNC patients but significantly less abnormal compared to the noncompacted segments (2.21 ± 0.63 vs. 2.01 ± 0.74, p < 0.05). No relationship was found between the number of noncompacted segments per patient and LV ejection fraction or end-diastolic volume. In the IVNC patients, noncompacted and compacted LV segments had comparable increased 3D regional volumes and reduced systolic function. Conclusions: These results suggest that systolic LV dysfunction observed in IVNC is not confined to noncompacted LV segments.

Inadequate immune regulatory function of CD4+CD25bright+FoxP3+ T cells in heart transplant patients who experience acute cellular rejection (Article)

2009-04-27T00:00:00Z

BACKGROUND.: CD4CD25FoxP3 regulatory T cells are suppressors of antigen-activated immune reactivity. Here, we assessed the clinically relevant role of these cells in the control of immune responses directed to a transplanted heart. METHODS.: We investigated the phenotype and function of peripheral CD4CD25FoxP3 T cells in heart transplant patients free from acute rejections (n=9) and in rejectors (n=12) before and during acute cellular rejection. RESULTS.: Between rejectors and nonrejectors, the proportion of CD4CD25 T cells and of FoxP3 cells within this population was comparable. Yet, CD4CD25FoxP3 T cells of rejectors had a higher CD127 expression than those of nonrejectors (P=0.0001). Depletion of CD4CD25 T cells from peripheral blood mononuclear cells increased the antidonor proliferative response of both nonrejectors (P≤0.0005) and rejectors (P≤0.03). In rejectors, however, only a 2-fold increase was measured, whereas the nonrejectors' response became 14 times higher (P=0.002). Reconstitution of CD4CD25 T cells only suppressed the overall antidonor proliferative response of CD25 responder cells of nonrejectors significantly (P=0.001). Moreover, the percentage inhibition of the response was higher in nonrejectors than in rejectors (P=0.02). Analyses of pretransplant samples revealed that CD4CD25 T cells of rejectors already had a lower suppressive capacity than those of nonrejectors before transplantation (P=0.04). CONCLUSION.: CD4CD25FoxP3 T cells of heart transplant patients who experience acute rejection had an up-regulated CD127 expression and an inadequate regulatory function compared with those of nonrejecting patients. Our observations suggest that the function of circulating CD4CD25FoxP3 regulatory T cells may be pivotal for the prevention of acute cellular rejection after clinical heart transplantation.

Diagnosis of biventricular non-compaction cardiomyopathy by real-time three-dimensional echocardiography (Article)

2009-03-01T00:00:00Z

Non-compaction of the ventricular myocardium is a recently recognized rare disorder of the endomyocardial morphogenesis. The disease can be characterized by systolic and diastolic heart failure, ventricular arrhythmias and systemic embolization. The present case suggests the clinical role of real-time three-dimensional echocardiography in the spatial evaluation of both ventricles in suspected biventricular non-compaction cardiomyopathy.

Donor-specific immune regulation by CD8+ lymphocytes expanded from rejecting human cardiac allografts (Article)

2009-02-01T00:00:00Z

To assess whether regulatory T cells are present in rejecting human cardiac allografts, we performed functional analyses of graft lymphocytes (GLs) expanded from endomyocardial biopsies (EMB; n = 5) with histological signs of acute cellular rejection. The GL cultures were tested for their proliferative capacity and regulatory activity on allogeneic-stimulated peripheral blood mononuclear cells (PBMC) of the patient (ratio PBMC:GLs = 5:1). Three of these GL cultures were hyporesponsive to donor antigens and suppressed the antidonor proliferative T-cell response of PBMC, but not the anti-third-party response. Interestingly, it was the CD8+GL subset of these cultures that inhibited the antidonor response (65-91% inhibition of the proportion of proliferating cells); the CD4+GLs of the expanded GL cultures were not suppressive. In conclusion, CD8+GLs expanded from rejecting human cardiac allografts can exhibit donor-specific immune regulatory activities in vitro. We suggest that during acute cellular rejection, GLs may not only consist of graft-destructing effector T cells, but also of cells of the CD8+type with the potential to specifically inhibit antidonor immune reactivity.

Intractable supraventricular tachycardia as first presentation of thoracic aortic dissection. Case report (Article)

2009-01-26T00:00:00Z

A patient presented with palpitations at the emergency department 3 days after a percutaneous coronary intervention complicated by dissection of the left anterior descending and circumflex coronary arteries. Physical examination revealed a high pulse rate and low blood pressure and the electrocardiogram demonstrated atrioventricular nodal re-entry tachycardia. This arrhythmia was eventually terminated by electrical cardioversion. Echocardiography demonstrated moderate aortic regurgitation and subsequent computed tomography showed a large Stanford type A aortic dissection. The patient was successfully operated and discharged 10 days after surgery.

Blood dendritic cell levels and phenotypic characteristics in relation to etiology of end-stage heart failure: Implications for dilated cardiomyopathy (Article)

2009-01-09T00:00:00Z

Background: Dysregulation of dendritic cell (DC) mediated immune responses towards auto-antigens, is considered an important feature in the maintenance of experimentally induced heart failure (HF). In order to evaluate the role of blood DCs in cardiomyopathies of different origins, we examined myeloid (mDC) and plasmacytoid (pDC) subset levels and maturation characteristics, according to HF severity and etiology in humans. Methods: Absolute numbers of mDCs and pDCs in 12 New York Heart Association (NYHA) class-II, 28 NYHA class III-IV HF patients and 18 healthy controls, were studied by 4-colour whole blood flow cytometry. Results: End-stage (NYHA III-IV) HF patients had comparable circulating DC subset levels to NYHA-II patients and controls. However, within the NYHA III-IV group total DC levels in patients with non-ischemic dilated cardiomyopathy (DCM) were higher (P < 0.001) than in patients with coronary artery disease (CAD), hypertrophic cardiomyopathy (HCM) or other HF etiology. This was due to a significant increase of primarily mDCs (P < 0.0001) and to a lesser extent of pDCs (P < 0.05) in idiopathic DCM patients, independent of systolic or diastolic cardiac dysfunction. Maturation marker CD83 and lymphoid homing chemokine receptor CCR7 surface expression was enhanced only on mDCs, but not pDCs from DCM patients (P < 0.05), compared to patients with CAD, HCM or other underlying cardiac pathophysiology. Conclusions: Total blood DC levels in end-stage HF are elevated in patients with DCM. Whole blood DC characterisation may lead to new insights into the pathophysiology of idiopathic DCM in humans.

Adverse reactions after the use of sulphur hexafluoride (SonoVue) echo contrast agent (Article)

2009-01-01T00:00:00Z

The aim of the present study was to analyse the adverse effects of SonoVue echo contrast in a consecutive series of 352 cardiac patients during a 4-year period. During 352 consecutive cardiac SonoVue studies, seven patients (2.0%) experienced adverse effects. Four patients (1.1%) had mild allergic reactions causing skin erythema and mild sinus tachycardia, and three patients (0.9%) experienced a severe allergic reaction resulting in (nonfatal) shock. The reported incidence of adverse effects of SonoVue echo contrast in this consecutive series of cardiac patients seems markedly higher than those reported in a company postmarketing analysis.

Evaluation of left atrial systolic function in noncompaction cardiomyopathy by real-time three-dimensional echocardiography (Article)

2008-12-01T00:00:00Z

Background: Noncompaction cardiomyopathy (NCCM) is a rare disorder with persistance of the embryonic pattern of myoarchitecture. NCCM is characterized by loosened, spongy myocardium associated with a high incidence of systolic and diastolic left ventricular (LV) dysfunction and heart failure (HF). It is known that LV dysfunction contributes to elevated left atrial (LA) and pulmonary vascular pressures, however atrial function has not been examined in NCCM. The objective of the present study was to assess LA systolic function characterized by LA ejection force (LAEF) in NCCM patients using real-time three-dimensional echocardiography (RT3DE) and to compare to control subjects. Methods: The study comprised 17 patients with an established diagnosis of NCCM and their results were compared to 17 healthy age-matched controls with no evidence of cardiovascular disease. Forty-one percent of NCCM patients were in NYHA functional class II/III HF. Previously proposed echocardiographic diagnostic criteria for NCCM were used. All patients underwent conventional two-dimensional echocardiography and RT3DE. LAEF was measured based on MA annulus diameter (LAEF3D-MAD) and area (LAEF3D-MAA) using RT3DE. Results: The presence and severity of mitral regurgitation were more frequent in NCCM patients than in control subjects. LV diameters and mitral annulus were significantly increased in NCCM patients. Compared with control subjects, both LAEF3D-MAD(3.8 ± 2.2 vs 2.3 ± 1.0 kdyne P < 0.05 and LAEF3D-MAA(12.7 ± 7.6 vs 4.9 ± 2.1 kdyne, P < 0.01) were significantly increased in NCCM patients. Conclusions: LAEF as a characteristic of LA systolic function is increased in NCCM patients compared to normal individuals. These results can suggest compensating left atrial work against the dysfunctional LV in NCCM patients.

Left ventricular solid body rotation in non-compaction cardiomyopathy: A potential new objective and quantitative functional diagnostic criterion? (Article)

2008-11-01T00:00:00Z

Background: Left ventricular (LV) twist originates from the interaction between myocardial fibre helices that are formed during the formation of compact myocardium in the final stages of the development of myocardial architecture. Since non-compaction cardiomyopathy (NCCM) is probably caused by intrauterine arrest of this final stage, it may be anticipated that LV twist characteristics are altered in NCCM patients, beyond that seen in patients with impaired LV function and normal compaction. Aims: The purpose of this study was to assess LV twist characteristics in NCCM patients compared to patients with non-ischaemic dilated cardiomyopathy (DCM) and normal subjects. Methods and results: The study population consisted of 10 patients with NCCM, 10 patients with DCM, and 10 healthy controls. LV twist was determined by speckle tracking echocardiography. In all controls and DCM patients, rotation was clockwise at the basal level and counterclockwise at the apical level. In contrast, in all NCCM patients the LV base and apex rotated in the same direction. Conclusions: These findings suggest that 'LV solid body rotation', with near absent LV twist, may be a new sensitive and specific, objective and quantitative, functional diagnostic criterion for NCCM.

Tele-guidance of chronic heart failure patients enhances knowledge about the disease. A multi-centre, randomised controlled study (Article)

2008-11-01T00:00:00Z

Background: New strategies are required to optimize care in increasing numbers of chronic heart failure patients. The aim of this randomised trial was to evaluate a remote guidance system. Methods: Intervention group patients received a home TV-channel providing educational materials. Tele-guidance was performed by a Medical Service Centre. Control group patients were followed by cardiologists and HF-nurses. Primary endpoints were total days in hospital for all causes and days alive and out of hospital. Secondary endpoints were: quality of life and knowledge of disease and self care. Results: 214 patients were enrolled, median age was 66 years, 89% had systolic LV dysfunction, and 90% were in NYHA class II or III. The mean LVEF was 31%. Over a mean follow-up duration of 288 days, there were 199 hospital admissions in 105 patients. Comparison of the groups revealed no differences for the primary outcomes or for QoL or self care behaviour. Knowledge about heart failure however, increased significantly more in the Intervention group (p < 0.001). Conclusion: Tele-guidance may play a role in the management of heart failure patients since it takes over some of the tasks of HF-nurses. This may facilitate delivery of optimal care to more patients with the same level of experienced staff.

FOXP3 mRNA expression analysis in the peripheral blood and allograft of heart transplant patients (Article)

2008-01-01T00:00:00Z

Previously, we demonstrated in heart transplant patients that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during an acute cellular rejection. In this study, we analyzed whether the FOXP3 gene expression in the peripheral blood also reflects anti-donor immune responses, and therefore may provide clues for non-invasive detection of non-responsiveness or acute rejection. We examined the FOXP3 expression patterns of peripheral blood mononuclear cells (PBMC; n = 69) of 19 heart transplant patients during quiescence and rejection in comparison with those of endomyocardial biopsies (EMB; n = 75) of 24 heart transplant patients. While the FOXP3 mRNA levels were abundantly expressed in rejecting EMB (ISHLT rejection grade > 1R) compared with EMB without histological evidence of myocardial damage (ISHLT rejection grade 0R-1R; p = 0.003), no association with rejection or non-responsiveness was found for the FOXP3 mRNA levels in the peripheral blood. Thus, in contrast to intragraft FOXP3 gene expression, the peripheral FOXP3 mRNA levels lack correlation with anti-donor immune responses in the graft, and, consequently, FOXP3 does not appear to be a potential candidate gene for non-invasive diagnosis of non-responsiveness or rejection.

Alterations in aortic elasticity in noncompaction cardiomyopathy (Article)

2008-01-01T00:00:00Z

Background: Noncompaction cardiomyopathy (NCCM) is a recently recognized disorder frequently associated with systolic and diastolic heart failures. This study was designed to examine aortic stiffness in NCCM patients and to compare these results to age- and gender-matched controls. Methods: A total of 20 patients with typical echocardiographic features of NCCM (age 38 ± 16 years, eight males) were investigated. Their results were compared to 20 age- and gender-matched controls. All subjects underwent a complete two-dimensional transthoracic echocardiographic examination. Systolic (SD) and diastolic (DD) ascending aortic diameters were recorded in M-mode at a level of 3 cm above the aortic valve from a parasternal long-axis view. Aortic stiffness index (β) was calculated as a characteristic of aortic elasticity, as ln(SBP/DBP)/[(SD - DD)/DD], where SBP and DBP are the systolic and diastolic blood pressures, respectively, and ln is the natural logarithm. Results: The number of noncompacted segments in the NCCM patients was 4.6 ± 2.0. NCCM patients had significantly increased left ventricular dimensions and reduced left ventricular ejection fraction. Compared to controls, aortic stiffness index (β) was significantly increased in NCCM patients (8.3 ± 5.2 vs. 3.5 ± 1.1, p < 0.001). Conclusion: Increased aortic stiffness can be observed in patients with NCCM with moderate to severe heart failure. These alterations may be due to neurohormonal changes in heart failure.

Predictors of Cardiac Events After Cardiac Resynchronization Therapy With Tissue Doppler-Derived Parameters (Article)

2007-12-01T00:00:00Z

Background: To evaluate the prognostic value of tissue Doppler imaging (TDI)-derived parameters (E/E′ ratio and Tei index) in heart failure (HF) patients who underwent cardiac resynchronization therapy (CRT). Methods and Results: The study comprised 74 consecutive HF patients (mean age 60 ± 11 years) who underwent CRT. Echocardiography including TDI measurements was performed in all patients at baseline and 3 months after CRT. During a median follow-up period of 720 days (range 210 to 1020 days), 21 patients (28%) had events (8 deaths, and hospitalization for HF in the remaining 13). From the baseline clinical and echocardiography data, univariable Cox-regressions analysis revealed that only diabetes (hazard ratio [HR] 3.703, P < .01), E/A ratio (HR 3.492, P < .001), and E/E′ ratio (HR 1.130, P < .001) were predictors for cardiac events. From the 3-month follow-up data, the E/A ratio (HR 2.988, P < .005), E/E′ ratio (HR 1.170, P < .001), left ventricular ejection fraction (HR 0.835, P < .01), deceleration time (HR 0.977, P < .05), and the Tei index (HR 15.784, P < .001) were predictors for cardiac events. After multivariable analysis, only diabetes (HR 5.544, P < .05), the 3-month E/E′ ratio (HR 1.229, P < .001), and change in Tei index (HR 32.174, P < .001) were independent predictors for cardiac events. Patients with a high baseline and 3-month follow-up E/E′ ratio had an 88% cardiac event rate. Conclusions: The Tei index and E/E′ ratio are independent predictors of poor response and cardiac events after CRT.

Cardiac β-myosin heavy chain defects in two families with non-compaction cardiomyopathy: Linking non-compaction to hypertrophic, restrictive, and dilated cardiomyopathies (Article)

2007-11-01T00:00:00Z

Cardiomyopathies are classified according to distinct morphological characteristics. They occur relatively frequent and are an important cause of mortality and morbidity. Isolated ventricular non-compaction or non-compaction cardiomyopathy (NCCM) is characterized by an excessively thickened endocardial layer with deep intertrabecular recesses, reminiscent of the myocardium during early embryogenesis. Aims: Autosomal-dominant as well as X-linked inheritance for NCCM has been described and several loci have been associated with the disease. Nevertheless, a major genetic cause for familial NCCM remains to be identified. Methods and Results: We describe, in two separate autosomal-dominant NCCM families, the identification of mutations in the sarcomeric cardiac β-myosin heavy chain gene (MYH7), known to be associated with hypertrophic cardiomyopathy (HCM), restricted cardiomyopathy (RCM), and dilated cardiomyopathy (DCM). Conclusion: These results confirm the genetic heterogeneity of NCCM and suggest that the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM with HCM, RCM, and DCM.

Intragraft FOXP3 mRNA expression reflects antidonor immune reactivity in cardiac allograft patients (Article)

2007-06-01T00:00:00Z

BACKGROUND. Regulatory FOXP3+ T cells control immune responses of effector T cells. However, whether these cells regulate antidonor responses in the graft of cardiac allograft patients is unknown. Therefore, we analyzed the gene expression profiles of regulatory and effector T-cell markers during immunological quiescence and acute rejection. METHODS. Quantitative real-time polymerase chain reaction was used to analyze mRNA expression levels in time-zero specimens (n=24) and endomyocardial biopsies (EMB; n=72) of cardiac allograft patients who remained free from rejection (nonrejectors; n=12) and patients with at least one histologically proven acute rejection episode (rejectors; International Society for Heart and Lung Transplantation [ISHLT] rejection grade >2; n=12). RESULTS. For all analyzed regulatory and effector T-cell markers, mRNA expression levels were increased in biopsies taken after heart transplantation compared with those in time-zero specimens. Posttransplantation, the FOXP3 mRNA levels were higher in EMB assigned to a higher ISHLT rejection grade than the biopsies with grade 0: the highest mRNA levels were detected in the rejection biopsies (rejection grade >2; P=0.003). In addition, the mRNA levels of CD25, glucocorticoid-induced TNF receptor family-related gene, cytotoxic T lymphocyte-associated antigen 4, interleukin-2, and granzyme B were also significantly higher in rejecting EMB than in nonrejecting EMB (rejection grade ≤2). This increase in expression levels in relation to the histological rejection grade was only observed in patients who developed an acute rejection episode; the mRNA levels of nonrejectors remained stable irrespective of ISHLT rejection grade. CONCLUSIONS. These observations suggest that, after clinical heart transplantation, FOXP3+ T cells do not prevent acute rejection, but rather are a response to antidonor effector T-cell activity.

Spectral pulsed-wave tissue Doppler imaging lateral-to-septal delay fails to predict clinical or echocardiographic outcome after cardiac resynchronization therapy (Article)

2007-02-01T00:00:00Z

Aims: The current study sought to assess if pre-implantation lateral-to-septal delay (LSD) ≥60 ms assessed by spectral pulsed-wave myocardial tissue Doppler imaging (PW-TDI) could predict successful long-term outcome after cardiac resynchronization therapy (CRT). Methods and results Sixty patients (72% males, mean age 59 ± 10 years) who were referred for CRT according to the ACC/ESC guidelines were enrolled in the study. All patients underwent spectral PW-TDI before and 1 year after CRT. Two left ventricular (LV) dyssynchrony time intervals, TOand TP(time to onset and peak of LV myocardial velocity, respectively), LSD were recorded. Left ventricular dyssynchrony was defined as LSD ≥60 ms. Clinical response was defined as an improvement in >1 NYHA class plus improvement in 6-min walk distance (6MWD) ≥25%, echocardiographic response was defined as a ≥15% reduction in LV end-systolic volume (LV-ESV). One year after CRT, 50 patients (83%) were clinical responders and 47 patients (78%) were echocardiographic responders. Both TOand TPLV dyssynchrony indices failed to predict echocardiographic CRT outcome. In addition, there were no significant differences between 'synchronous' and 'dyssynchronous' patient populations at baseline or follow-up in either clinical (NYHA class and 6MWD) or echocardiographic (LV ejection fraction, LV end-diastolic, and end-systolic) variables. Conclusion: The great majority of patients referred for CRT benefit clinically from it. However, spectral PW-TDI failed to predict CRT outcome. When PW-TDI dyssynchrony was applied for selection of proper CRT patients, up to 80-86% of the patients with synchronous LSD that had proven clinical and echocardiographic benefit from CRT would have been denied CRT.

Wide spectrum of presentation and variable outcomes of isolated left ventricular non-compaction (Article)

2007-01-01T00:00:00Z

Objectives: To investigate diagnostic routes, echocardiographic substrates, outcomes and prognostic factors in patients with isolated ventricular non-compaction (IVNC) identified by echocardiographic laboratories with referral from specialists and primary care physicians. Patients and design: Since 1991, all patients with suspected IVNC were flagged and followed up on dedicated databases. Patients were divided into symptom-based and non-symptom-based diagnostic subgroups. Results: 65 eligible patients were followed up for 6-193 months (mean 46 (SD 44). In 53 (82%) patients, IVNC was associated with variable degrees of left ventricular (LV) dilatation and hypokinesia, and in the remaining 12 (18%) LV volumes were normal. Diagnosis was symptom based in 48 (74%) and non-symptom based in 17 (26%) (familial referral in 10). The non-symptom-based subgroup was characterised by younger age, lower prevalence of ECG abnormalities, better systolic function and lower left atrial size, whereas the extent of non-compaction was not different. No major cardiovascular events occurred in the non-symptom-based group, whereas 15 of 48 (31%) symptomatically diagnosed patients experienced cardiovascular death or heart transplantation (p = 0.01, Kaplan-Meier analysis). Independent predictors of cardiovascular death or heart transplantation were New York Heart Association class HI-IV, sustained ventricular arrhythmias and left atrial size. Conclusions: IVNC is associated with a broad spectrum of clinical and pathophysiological findings, and the overall natural history and prognosis may be better than previously thought. Adult patients with incidental or familial discovery of IVNC have an encouraging outlook, whereas those who have symptoms of heart failure, a history of sustained ventricular tachycardia or an enlarged left atrium have an unstable course and more severe prognosis.