Clinical Implementation of Cardiac Resynchronization Therapy-Regional Disparities across Selected ESC Member Countries.

BACKGROUND: The present analysis aimed to estimate the penetration of cardiac resynchronization therapy (CRT) on the basis of the prevalence and incidence of eligible patients in selected European countries and in Israel. METHODS AND RESULTS: The following countries were considered: Italy, Slovakia, Greece, Israel, Slovenia, Serbia, the Czech Republic, Poland, Romania, Hungary, Ukraine, and the Russian Federation. CRT penetration was defined as the number of patients treated with CRT (CRT patients) divided by the prevalence of patients eligible for CRT. The number of CRT patients was estimated as the sum of CRT implantations in the last 5 years, the European Heart Rhythm Association (EHRA) White Book being used as the source. The prevalence of CRT indications was derived from the literature by applying three epidemiologic models, a synthesis of which indicates that 10% of heart failure (HF) patients are candidates for CRT. HF prevalence was considered to range from 1% to 2% of the general population, resulting in an estimated range of prevalence of CRT indication between 1000 and 2000 patients per million inhabitants. Similarly, the annual incidence of CRT indication, representing the potential target population once CRT has fully penetrated, was estimated as between 100 and 200 individuals per million. The results showed the best CRT penetration in Italy (47-93%), while in some countries it was less than 5% (Romania, Russian Federation, and Ukraine). CONCLUSION: CRT penetration differs markedly among the countries analyzed. The main barriers are the lack of reimbursement for the procedure and insufficient awareness of guidelines by the referring physicians

The fusion band in V1: a simple ECG guide to optimal resynchronization? An echocardiographic case report

BACKGROUND: Patients with left bundle branch block have a preserved right bundle branch conduction and the efficacy of left ventricular pacing could be explained with the fusion between artificial pulse delivered in the left lateral wall and the spontaneous right ventricular activation. Moreover, the efficacy of left ventricular pacing could be enhanced with an optimal timing between the spontaneous right ventricular activation and the left ventricular pulse. CASE PRESENTATION: We evaluated a patient (male, 47 yrs) with surgically corrected mitral regurgitation, sinus rhythm and left bundle branch block, heart failure (NYHA class III) despite medical therapy and low ejection fraction (25%): he was implanted with a biventricular device. We programmed ventricular pacing only through the left ventricular lead. We defined what we called electrocardiographic "fusion band" as follow: programming OFF the stimulator, we recorded the native electrocardiogram and measured, through the device, the intrinsic atrioventricular interval. Then, atrioventricular interval was progressively shortened by steps of 20 ms down to 100 ms. Twelve leads electrocardiogram was recorded at each step. The fusion band is the range of AV intervals at which surface electrocardiogram (mainly in V1 lead) presents an intermediate morphology between the native left bundle branch block (upper limit of the band) and the fully paced right bundle branch block (lower limit). The patient underwent echocardiographic examination at each atrioventricular interval chosen inside the fusion band. The following parameters were evaluated: ejection fraction, diastolic filling time, E wave deceleration time, aortic velocity time integral and myocardial performance index. All the echocardiographic parameters showed an improvement inside the fusion band, with a "plateau" behaviour. As the fusion band in this patient ranged from an atrioventricular delay of 200 ms to an atrioventricular delay of 120 ms, we chose an intermediate atrioventricular delay of 160 ms, presuming that this might guarantee the persistence of fusion even during any possible physiological (autonomic, effort) atrioventricular conduction variation. CONCLUSION: In this heart failure patient with left bundle branch block, tailoring of the atrioventricular interval resynchronized myocardial contraction with left ventricular pacing alone, utilizing a sensed right atrial activity and the surface electrocardiographic pattern

Dysregulation of Mitochondrial Dynamics and the Muscle Transcriptome in ICU Patients Suffering from Sepsis Induced Multiple Organ Failure

BACKGROUND: Septic patients treated in the intensive care unit (ICU) often develop multiple organ failure including persistent skeletal muscle dysfunction which results in the patient's protracted recovery process. We have demonstrated that muscle mitochondrial enzyme activities are impaired in septic ICU patients impairing cellular energy balance, which will interfere with muscle function and metabolism. Here we use detailed phenotyping and genomics to elucidate mechanisms leading to these impairments and the molecular consequences. METHODOLOGY/PRINCIPAL FINDINGS: Utilising biopsy material from seventeen patients and ten age-matched controls we demonstrate that neither mitochondrial in vivo protein synthesis nor expression of mitochondrial genes are compromised. Indeed, there was partial activation of the mitochondrial biogenesis pathway involving NRF2alpha/GABP and its target genes TFAM, TFB1M and TFB2M yet clearly this failed to maintain mitochondrial function. We therefore utilised transcript profiling and pathway analysis of ICU patient skeletal muscle to generate insight into the molecular defects driving loss of muscle function and metabolic homeostasis. Gene ontology analysis of Affymetrix analysis demonstrated substantial loss of muscle specific genes, a global oxidative stress response related to most probably cytokine signalling, altered insulin related signalling and a substantial overlap between patients and muscle wasting/inflammatory animal models. MicroRNA 21 processing appeared defective suggesting that post-transcriptional protein synthesis regulation is altered by disruption of tissue microRNA expression. Finally, we were able to demonstrate that the phenotype of skeletal muscle in ICU patients is not merely one of inactivity, it appears to be an actively remodelling tissue, influenced by several mediators, all of which may be open to manipulation with the aim to improve clinical outcome. CONCLUSIONS/SIGNIFICANCE: This first combined protein and transcriptome based analysis of human skeletal muscle obtained from septic patients demonstrated that losses of mitochondria and muscle mass are accompanied by sustained protein synthesis (anabolic process) while dysregulation of transcription programmes appears to fail to compensate for increased damage and proteolysis. Our analysis identified both validated and novel clinically tractable targets to manipulate these failing processes and pursuit of these could lead to new potential treatments