Synergistic effects of cardiac resynchronization therapy and drug up-titration in heart failure. is this enough?

This editorial refers to ‘Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival’, by C.T. Witt et al., on page 18

A next-generation sequencing approach to identify gene mutations in early-and late-onset hypertrophic cardiomyopathy patients of an Italian cohort

Sequencing of sarcomere protein genes in patients fulfilling the clinical diagnostic criteria for hypertrophic cardiomyopathy (HCM) identifies a disease-causing mutation in 35% to 60% of cases. Age at diagnosis and family history may increase the yield of mutations screening. In order to assess whether Next-Generation Sequencing (NGS) may fulfil the molecular diagnostic needs in HCM, we included 17 HCM-related genes in a sequencing panel run on PGM IonTorrent. We selected 70 HCM patients, 35 with early (≤25 years) and 35 with late (≥65 years) diagnosis of disease onset. All samples had a 98.6% average of target regions, with coverage higher than 20× (mean coverage 620×). We identified 41 different mutations (seven of them novel) in nine genes: MYBPC3 (17/41 = 41%); MYH7 (10/41 = 24%); TNNT2, CAV3 and MYH6 (3/41 = 7.5% each); TNNI3 (2/41 = 5%); GLA, MYL2, and MYL3 (1/41=2.5% each). Mutation detection rate was 30/35 (85.7%) in early-onset and 8/35 (22.9%) in late-onset HCM patients, respectively (p < 0.0001). The overall detection rate for patients with positive family history was 84%, and 90.5% in patients with early disease onset. In our study NGS revealed higher mutations yield in patients with early onset and with a family history of HCM. Appropriate patient selection can increase the yield of genetic testing and make diagnostic testing cost-effective

SENSING THE LAND SUBSIDENCE IN THE VENICE LAGOON BY INTERFEROMETRIC POINT TARGET ANALYSIS

Land subsidence is a severe geologic hazard threading the lowlying coastal areas worldwide. Monitoring land subsidence has been significantly improved over the last few years by space borne earth observation techniques based on SAR (Synthetic Aperture Radar) Interferometry. Within the INLET Project, funded by Magistrato alle Acque di Venezia – Venice Water Authority (VWA) and Consorzio Venezia Nuova (CVN), we have used the Interferometric Point Target Analysis (IPTA) to characterize the ground displacements within the Venice Lagoon. IPTA measures the movement of backscattering objects (point targets, PT) at the ground surface which persistently reflect radar signal emitted by the SAR antenna. For this study 80 ERS-1/2 and 44 ENVISAT scenes recorded from 1992 to 2005 and from 2003 to 2007, respectively, have been processed by IPTA. High reliable land subsidence data have been detected for thousands of PT located on the lagoon margins, along the littorals, in major and small islands, and on single anthropogenic structures scattered within the lagoon. On the average, land subsidence ranges from less than 1 mm/year to 5 mm/year, with some PT that exhibit values also larger than 10 mm/year depending on both the local geologic conditions and anthropogenic activities. A network of few tens of artificial square trihedral corner reflectors (TCR) has been established before summer 2007 to monitor land subsidence in the inner lagoon areas where natural reflectors completely lack (e.g., on the salt marshes). The first interferometric results on the TCR appear very promising

Autonomic cardiovascular control and cardiac arrhythmia in two pregnant women with hypertrophic cardiomyopathy: Insights from ICD monitoring

In women with hypertrophic cardiomyopathy (HCM), pregnancy prompts major changes in hemodynamic and cardiac autonomic function that may precipitate heart failure (HF) or increase the risk of cardiac arrhythmia.We report the clinical follow-up of two patients with non-obstructive HCM implanted with a cardioverter defibrillator (ICD) allowing for continuous analysis of heart rate (HR), heart rate variability (HRV) and cardiac arrhythmia throughout the entire course of pregnancy.Both patients experienced increased HR and decreased HRV from the early stages of pregnancy, which persisted until delivery. Premature ventricular contractions (PVCs) and runs of non-sustained ventricular tachycardia (NSVT) reached a peak in the second and third trimesters, concurrent with sympathetic hyperactivity. In one patient with baseline NYHA class II HF symptoms, increased PVCs and NSVT were consistent with the deterioration of HF, supporting the decision to bring the delivery forward. While both patients experienced a persistent increase in sympathetic tone and ventricular ectopic activity, no life-threatening arrhythmias were documented.During pregnancy, patients with hypertrophic cardiomyopathy develop progressive neuroautonomic imbalance, prompting an increase in non-sustained ventricular arrhythmia. This enhanced arrhythmia burden warrants close follow-up and rhythm assessment during the third trimester, especially in women who have heart failure symptoms before pregnancy. Implantable cardioverter defibrillators provide a continuous analysis of heart rate variability and arrhythmia burden that supports therapeutic decision-making during follow-up. Resumo: Em mulheres com miocardiopatia hipertrófica, a gravidez aumenta as variações hemodinâmicas e as alterações da função autonómica cardíaca que podem provocar insuficiência cardíaca ou aumentar o risco de arritmia. Reportamos o acompanhamento clínico de duas pacientes com miocardiopatia hipertrófica não obstrutiva, ambas implantadas com cardioversor-desfibrilhador (CID). A monitoração com CID permite a análise contínua da frequência cardíaca, da variabilidade da frequência cardíaca (VFC) e da arritmia durante toda a gravidez. As duas pacientes manifestaram aumentos da FC e diminuições da VFC desde o início da gravidez até ao parto. Observou-se um pico de frequência de extrassístoles ventriculares (EV) e de taquicardias ventriculares não sustentadas (TVNS) no segundo e terceiro trimestres da gestação, em correspondência da hiperatividade simpática. Numa das pacientes com classe funcional NYHA II, antes da gravidez, o aumento de EV e de TVNS contemporaneamente ao agravamento da insuficiência cardíaca levou à decisão de antecipar o parto. As duas pacientes demonstraram um aumento persistente da atividade simpática e da atividade ectópica ventricular, não existiram casos de arritmias ventriculares malignas. Durante a gravidez as pacientes com miocardiopatia hipertrófica desenvolvem um progressivo desequilíbrio autonómico que causa um aumento das arritmias ventriculares não sustentadas. O aumento do risco arrítmico necessita de um constante e frequente controle clínico e do ritmo cardíaco durante o terceiro trimestre, especialmente em mulheres com sintomas de insuficiência cardíaca antes da gravidez. O cardioversor-desfibrilhador implantável fornece uma análise continua da variabilidade da frequência cardíaca e das arritmias que podem apoiar as decisões terapêuticas durante a gravidez. Keywords: Hypertrophic cardiomyopathy, Pregnancy, Implantable cardioverter defibrillator, Heart rate variability, Ventricular arrhythmia, Palavras-chave: Miocardiopatia hipertrófica, Gravidez, Cardioversor-desfibrilhador implantável, Variabilidade da frequência cardíaca, Arritmia ventricula

Oxidative stress and cardiovascular disease

The endothelium is one of the most important, and certainly the most extensive, organs involved in cardio- vascular homeostasis. The endothelium-derived vasoactive factors inhibiting smooth muscular cells contraction and proliferation, and platelet function, include nitric oxide (NO), prostacyclin and endothelial-derived hyperpolarizing factor. However, endothelial cells can also produce vasoconstrictive, proaggregant, promitogen mediators, such as thromboxane A2, prostaglandin H2, endothelin 1, and angiotensin II. Therefore, any impair- ment of endothelial function may trigger the typical chain of events of atherogenesis, characterised by vasocon- striction, cellular proliferation and thrombosis. In this regard, the biological link between endothelial dysfunction and atherosclerosis is a reduced bioavailability of NO. However, the precise mechanisms by which the endothelial dysfunction occurs remain still unclear. A decreased bioavailability of NO can be caused by its enhanced reactive oxygen species (ROS) breakdown. Oxidative stress may represent a common mechanism by which different cardiovascular risk factors cause endothelial dysfunction and trigger atherothrombotic process

Toxoplasmosis in Kosovo pregnant women

This study presents the initial results of a collaborative project aimed at the evaluation of Toxoplasma seroprevalence in a population of Kosovar pregnant women. The serum samples of 334 pregnant women were tested to detect IgG, IgM, IgG avidity for toxoplasmosis. Data regarding age, occupation, area of origin and education were also obtained for the pregnant women examined; 97/334 (29.4%) resulted positive for IgG antibodies, four of whom (4.1%) were also positive for IgM, (1.2% of the total population examined). All four IgM-positive pregnant women also demonstrated low avidity tests. The rate of IgG seroprevalence found in our study was lower than that observed in various European countries, especially those of western Europe. Conversely, the percentage of recent infections was higher than expected. The higher rate of infections could be the result of a recent toxoplasmosis epidemic in Kosovo, most likely due to the altered hygienic conditions caused by the forced transfer of the ethnic-Albanian population from an area of low (Serbia) to high (Kosovo) toxoplasmosis prevalence

Viral hepatitis, HIV, human herpes virus and Treponema pallidum infection in haemodialysis patients from Kosovo, 2005.

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Exploring the influence of takotsubo syndrome on oncologic patients' mortality

It has been reported that patients affected by takotsubo syndrome (TTS) with a concurrent diagnosis of cancer suffer from greater mortality as compared to their non-cancer counterpart. It remains unclear whether TTS worsens the prognosis of cancer patients as well. Aim of this study was to compare outcomes of cancer patients with and without TTS. We combined data from two independent cohorts: one consisted of a prospective multicentre TTS registry; the second cohort consisted of all oncologic patients from two Cardio-Oncology Outpatient Clinics, who did not have cardiovascular conditions at the time of the cardio-oncologic visit. From the TTS registry, we selected patients with cancer (cancer-TTS patients). Next, we matched these patients with those from the cardio-oncologic cohort (cancer non-TTS patients) in a 1:2 fashion by age, sex, and type and cancer staging. Study endpoint was all-cause mortality. Among 318 TTS patients, 42 (13%) had a concurrent diagnosis of cancer. Characteristics of cancer-TTS patients and of the 84 matched cancer non-TTS subjects were comparable with the exception of diabetes mellitus, which was more common in cancer non-TTS patients. All-cause mortality was similar between cancer-TTS and cancer non-TTS patients. At Cox regression analysis TTS was not associated with mortality (OR 1.4, 95% CI 0.6-3.3, p = 0.43). Our findings show that even in the presence of acute heart failure due to TTS, the prognosis of oncologic patients is driven by the malignancy itself. Our results may prove useful for integrated management of cardio-oncologic patients