Influence of the atrio-ventricular delay optimization on the intra left ventricular delay in cardiac resynchronization therapy

BACKGROUND: Cardiac Resynchronization Therapy (CRT) leads to a reduction of left-ventricular dyssynchrony and an acute and sustained hemodynamic improvement in patients with chronic heart failure. Furthermore, an optimized AV-delay leads to an improved myocardial performance in pacemaker patients. The focus of this study is to investigate the acute effect of an optimized AV-delay on parameters of dyssynchrony in CRT patients. METHOD: 11 chronic heart failure patients with CRT who were on stable medication were included in this study. The optimal AV-delay was defined according to the method of Ismer (mitral inflow and trans-oesophageal lead). Dyssynchrony was assessed echocardiographically at three different settings: AVD(OPT); AVD(OPT)-50 ms and AVD(OPT)+50 ms. Echocardiographic assessment included 2D- and M-mode echo for the assessment of volumes and hemodynamic parameters (CI, SV) and LVEF and tissue Doppler echo (strain, strain rate, Tissue Synchronisation Imaging (TSI) and myocardial velocities in the basal segments) RESULTS: The AVD(OPT )in the VDD mode (atrially triggered) was 105.5 ± 38.1 ms and the AVD(OPT )in the DDD mode (atrially paced) was 186.9 ± 52.9 ms. Intra-individually, the highest LVEF was measured at AVD(OPT). The LVEF at AVD(OPT )was significantly higher than in the AVD(OPT-50)setting (p = 0.03). However, none of the parameters of dyssynchrony changed significantly in the three settings. CONCLUSION: An optimized AV delay in CRT patients acutely leads to an improved systolic left ventricular ejection fraction without improving dyssynchrony

Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease

BackgroundWe investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD).MethodsIn total 430 patients with CVD and healthy persons were enrolled in the current study. Peripheral blood was drawn by routine venipuncture procedure. Plasma and peripheral blood mononuclear cells (PBMCs) were collected. Cell-free genomic DNA (cfDNA) and leukocytic genomic DNA (leuDNA) were extracted from plasma and PBMCs, respectively. Relative telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) were analyzed using quantitative polymerase chain reaction. Endothelial function was evaluated by measuring flow-mediated dilation (FMD). The correlation between TL of cfDNA (cf-TL), mtDNA-CN of cfDNA (cf-mtDNA), TL of leuDNA (leu-TL), mtDNA-CN of leuDNA (leu-mtDNA), age, and FMD were analyzed based on Spearman's rank correlation. The association between cf-TL, cf-mtDNA, leu-TL, leu-mtDNA, age, gender, and FMD were explored using multiple linear regression analysis.Resultscf-TL positively correlated with cf-mtDNA (r = 0.1834, P = 0.0273), and leu-TL positively correlated with leu-mtDNA (r = 0.1244, P = 0.0109). In addition, both leu-TL (r = 0.1489, P = 0.0022) and leu-mtDNA (r = 0.1929, P < 0.0001) positively correlated with FMD. In a multiple linear regression analysis model, both leu-TL (β = 0.229, P = 0.002) and leu-mtDNA (β = 0.198, P = 0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (β = −0.426, P < 0.0001).ConclusionTL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction

Positive cardiac troponin I and T and chest pain in a patient with iatrogenic hypothyroidism and no coronary artery disease

We report about a 41-year old male patient who presented to the emergency room with acute chest pain, exertion dyspnoea, muscle stiffness, myalgia and adynamia. There was no history of coronary artery disease but known arterial hypertension and insulin dependent diabetes mellitus. Four weeks before submission the patient had been thyroidectomized after he had been diagnosed with papillary thyroid carcinoma and was now awaiting further radioiodine therapy. The thyroid-stimulating hormone level was markedly elevated to 67 mU/l (normal range 0.27-4.20 mU/l) and fT4 significantly reduced to 0.19 ng/ml (normal range 0.9-1.9 ng/ml). CK was elevated to 328 U/l, cardiac Troponin I (Stratus(R) CS) above the threshold with 0.13 mug/l and Elecsys(R) third generation troponin T above the threshold with 0.04 mug/l. The electrocardiogram showed a normal sinus rhythm and did not reveal any signs of ST-elevation or -depression. During follow-up a cardiac MRI was performed, showing normal dimensions and function but a very small area of diffuse myocardial damage, atypical of ischemic injury. In coronary angiography normal coronary arteries were found. We conclude that cardiac troponins I and T may be elevated in severe hypothyroidism without coronary artery disease due to diffuse myocardial injury which can be imaged by MRI

Therapeutic arteriogenesis in peripheral arterial disease: combining intervention and passive training

The prevalence of peripheral arterial disease (PAD) is on the rise in an aging population, significantly affecting quality of life, morbidity and mortality. Besides medical treatment and surgical or interventional revascularization, supervised exercise programs are a primary treatment modality for PAD. Training may significantly increase pain-free walking time (+ 180 %) while avoiding the associated complications of (repeated) invasive revascularization. Training effects rely on an improvement of risk factor management, muscle function, economy of movement, hemorheology, vascular growth and collateral vessel growth. Exercise training upregulates pulsatile fluid shear stress on the vascular endothelium, prompting an improvement of endothelial function (eNOS, NO) and an outgrowth of preexistent collaterals (arteriogenesis) to functional conductance arteries outside the ischemic area at risk. However, the necessary intense minimum training intervals compromise patient compliance, and the impaired functional status of many PAD patients limits active exercise training. Strategies are necessary to a) increase training compliance, b) make the benefits of exercise training available to patients unable to exercise actively and c) therapeutically enhance the adaptive growth of biological bypasses (arteriogenesis). A modified form of "passive exercise training" derived from enhanced external counterpulsation (low-pressure ECP) which was originally developed for the therapy of heart failure, may prove to be an option for this group of patients. Therefore, this review article suggests a tailored combination therapy, consisting of a facilitating revascularization procedure to restore arterial inflow, succeeded by supervised exercise training, which has yielded promising therapeutic results in clinical trials. Further studies, using appropriate imaging methods and controls, are under way to (a) establish the efficacy of low-pressure EECP in PAD patients and (b) to directly correlate training-induced improvements of collateral flow to the functional improvements seen with exercise training