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

Safety, Efficacy and Evidence Base for Use of the Subcutaneous Implantable Cardioverter Defibrillator

The trans-venous implantable cardioverter defibrillator (TV-ICD) is effective in treating life-threatening ventricular arrhythmia and reduces mortality in high-risk patients. However, there are significant short- and long-term complications that are associated with intravascular leads. These shortcomings are mostly relevant in young patients with long life expectancy and low risk of death from non-arrhythmic causes. Drawbacks of trans-venous leads recently led to the development of the entirely subcutaneous implantable cardioverter defibrillator (S-ICD). The S-ICD does not require vascular access or permanent intravascular defibrillation leads. Therefore, it is expected to overcome many complications associated with conventional ICDs. This review highlights data on safety and efficacy of the S-ICD and is envisioned to help in identifying the role of this device in clinical practice

On the Lagrangian formulation of the double copy to cubic order

We investigate the Lagrangian formulation of the double-copy correspondence between gauge theories and gravity, up to the cubic order. Building on the definition of the double-copy field as a convolution of two vectors, we obtain free gravitational Lagrangians as products of two Yang-Mills Lagrangians, in a form amenable to be easily extended to the massive case. We discuss the origin of these results from tensionless strings and show the existence of gauge fixings that mix the two spin-one sectors and lead to an alternative, especially simple, version of the free Lagrangian. We then construct cubic vertices for the full double-copy multiplet, comprising a graviton, a two-form and a scalar particle, by means of the Noether procedure. Both at the free and at the cubic level the result gets uniquely fixed only upon imposing, on top of gauge invariance, a left-right Lorentz symmetry ruling contraction of indices among double-copy fields. Whereas the outcome nicely matches the cubic interactions of $\mathcal{N}=0$ supergravity, including the gauge-invariant coupling between the scalar particle and the two-form, such a twofold Lorentz symmetry seems to conflict with the perturbative reconstruction of space-time geometry.Comment: 28 pages. minor editing, matches published versio

Distinguishing hypertension from hypertrophic cardiomyopathy as a cause of left ventricular hypertrophy

Distinguishing Hypertension From Hypertrophic Cardiomyopathy as aCause of Left Ventricular HypertrophyIn most hypertensive patients, left ventricular (LV) wallthickness is normal or only mildly increased (≤13 m

Old and new therapeutic solutions in the treatment of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the myocardium that is relatively common in the general population, with an autosomal dominant inheritance as a genetic basis. Clinical and natural history pathways can be very different among patients with HCM. Treatment strategies have made very important advances in the last two decades, especially reducing cases of sudden death through effective risk stratification and the use of implantable defibrillators. Heart failure has become the predominant cause of morbidity and mortality in patients with HCM, being responsible for as many as 60% of disease-related deaths. HCM is most often characterized by the presence of left ventricular outflow tract (LVOT) obstruction, and this obstruction is the most frequent cause of impaired exercise tolerance in HCM and a strong independent predictor of heart failure progression and mortality. The different treatment strategies of LVOT obstruction in HCM are discussed below: surgical, invasive, and the more recent pharmacological

Multi-modality imaging approach in a challenging case of surgically corrected partial anomalous pulmonary venous return and atrial tachycardia treated with radiofrequency ablation

Pulmonary anomalous venous return (PAPVR) is defined as a congenital anomaly in which at least one but not all of the pulmonary veins abnormally drain into a systemic vein or directly into the right atrium. Signs and symptoms related to this condition are due to the hemodynamic abnormalities secondary to left-to-right shunt and the possible presence of other associated cardiac anomalies (e.g., sinus venous atrial septal defect). Therefore, depending on the extent of the shunt, the clinical presentation of PAPVR is variable, ranging from asymptomatic patients to patients affected by severe heart failure with right-sided volume overload. PAPVR with a clinically significant shunt should be referred for surgical correction with different techniques depending on the presence of associated cardiac anomalies. We are presenting a case of partial anomalous venous return (PAPVR) in a 66-year-old man who underwent surgery 26 years ago to correct an anomalous venous connection between the right superior pulmonary vein (RSPV) and the superior vena cava (SVC) through a veno-atrial baffle. The patient was admitted to the emergency department due to atrial tachycardia. Trans-thoracic echocardiography (TTE) showed a dilated right ventricle (RV) with mild RV systolic dysfunction and pulmonary hypertension.Cardiac magnetic resonance (CMR) further confirmed the findings described by TTE and also demonstrated areas of fibrosis replacement in the hinge points. Cardiac computed tomography (CCT) was able to accurately depict and evaluate the surgically created veno-atrial baffle and also showed an anomalous connection between the left superior pulmonary vein (LSPV) and the brachiocephalic vein (BCV) through a vertical vein. The patient was successfully treated with radiofrequency ablation for his arrhythmia

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

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

Computed tomography-based identification of ganglionated plexi to guide cardioneuroablation for vasovagal syncope

This study shows that CT-based EFP-guided CNA for CI-VVS is feasible, can assist RF delivery with high precision, and has the potential to overcome the interpatient variability that affects CNA when performed solely by anatomic landmarks. Further larger studies with longer follow-up are required to improve CT-based identification of GPs and our understanding of GP pathophysiology

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