Aging can be seen as process characterized by accumulation of oxidative stress induced damage. Oxidative stress derives from different endogenous and exogenous processes, all of which ultimately lead to progressive loss in tissue and organ structure and functions. The oxidative stress theory of aging expresses itself in age-related diseases. Aging is in fact a primary risk factor for many diseases and in particular for cardiovascular diseases and its derived morbidity and mortality. Here we highlight the role of oxidative stress in age-related cardiovascular aging and diseases. We take into consideration the molecular mechanisms, the structural and functional alterations, and the diseases accompanied to the cardiovascular aging process.

Background In the past years, different devices have been investigated to help in identifying early decompensation events in patients with heart failure (HF) and reduced ejection fraction (EF), reducing hospital admissions. In this report, we present the first patient experience with levosimendan infusion led by CardioMEMS. Case summary A 68-year-old man with HF and reduced EF with more than 20 hospitalizations for exacerbation of HF was enrolled in our HF Clinic from October 2017. Echocardiogram showed a dilated left ventricle with severely reduced EF (29%) and increased pulmonary artery systolic pressure (40 mmHg). From October 2017 to May 2019, the patient went through numerous hospitalizations, despite optimal medical therapy; subsequently, was adopted a strategy of levosimendan infusions guided by CardioMEMS. Levosimendan infusions improved haemodynamic and pressure profiles. The patient was monitored daily by CardioMEMS, and from June to December 2019, he had only two hospitalizations scheduled for levosimendan infusion and none for HF exacerbation. Discussion Our case supports the combination of CardioMEMS and levosimendan for the optimal management of patients with advanced HF. These results further strengthen the development of a randomized clinical trial to demonstrate the clinical usefulness of this device in combination with the levosimendan infusion programme in advanced HF patients.

Methods and results A 58 years-old man was admitted to our intensive care unit for syncope due to inconstant capture of epicardial ventricular lead. His cardiovascular history began 20 years before when he underwent single chamber pacemaker implantation with insertion of a passive fixation ventricular lead for symptomatic complete atrio ventricular block (AVB). Electrical parameters were good at implantation. However, during follow-up a gradual and progressive increase of pacing threshold occurred, with no changes in impedance values, finally leading to complete loss of ventricular capture. Hence, 2 years later, the lead was extracted and a new transvenous ventricular lead was placed in septal position. All electrical parameters were optimal at the end of the procedure. However, in the following months threshold values gradually increased as previously observed. The referring clinicians decided to surgically extract both the device and transvenous lead and to implant an epicardial ventricular lead connected to an abdominal generator. The pacemaker worked properly for about 17 years until he was transferred to our institution with evidence of inconstant lead capture at maximum pacing outputs. A temporary transvenous pacemaker was immediately inserted. Clinical examination, laboratory exams, and echocardiography were normal. Cardiac magnetic resonance (MRI) was not feasible due to the epicardial lead. Thus, in order to obtain cardiac substrate characterization, we decided to perform high density multielectrode voltage mapping of the right ventricular endocardium with HD Grid multielectrode mapping catheter (HD Grid mapping catheter sensor enabled, Abbott Technologies, Minneapolis, MN). Electroanatomic voltage map allows distinction of areas of healthy myocardium (>1.5 mV) from scar tissue (<0.5 mV). Unexpectedly, voltage mapping highlighted no scar zones, showing a globally normal endomyocardial surface. Therefore, a new endocavitary pacemaker was inserted in right prepectoral region and an active fixation right ventricular lead was placed on mid-ventricular septum. A backup pacing lead was placed in a more apical position in an area of endocardial healthy myocardium. Post-procedural sensing, impedance and capture threshold were optimal (0.3 V × 0.4 ms for mid-septal lead and 0.3 × 0.4 ms for the other one). At 1 month follow-up mid-septal lead’s threshold was slightly increased (1.0 V × 0.4 ms) and further increase was observed at 3-month outpatient visit (1.75 V × 0.4 ms). Capture threshold of the other lead and other parameters were stable. The patient received remote monitoring for home surveillance of the implanted system. Home monitoring shows a trend toward a progressive increase of pacing threshold of the mid-septal lead and stable value of the other electrode. Conclusions The present report suggests an innovative use of high-density mapping with HD Grid catheter to characterize endocardial right ventricular myocardium in a patient with contraindication to cardiac MRI and recurrent failure of previous implanted pacing systems for unknown reason and to guide effective lead placement in areas of normal endocardial voltage. Combined use of telemedicine and high-resolution mapping technique allowed us to avoid unnecessary high risk reintervention for novel epicardial lead placement.

A 53-years old man presented to our institution with a diagnosis of decompensated heart failure NYHA Class IV. He had a history of ischaemic heart disease with severe biventricular dysfunction, diabetes, hypertension, dyslipidaemia, advanced chronic kidney disease, previous explanation of dual-chamber implantable electronic device (ICD) due to endocarditis and subsequent implantation of subcutaneous ICD in primary prevention. Home therapy included uptitrated angiotensin-converting enzyme inhibitor, β-blocker, loop-diuretic, spironolactone, acetylsalicylic acid, and oral hypoglycemics. Clinical examination showed signs and symptoms of systemic and pulmonary congestion with pleural effusion and ascites. Echocardiography revealed diffuse left ventricular (LV) hypokinesis with an ejection fraction (EF) of 25%, severe right ventricular dysfunction and increased filling pressures. He was treated with high dose of i.v. diuretics with mild improvement of dyspnoea. However, haemodynamic stability was labile with worsening of symptoms as soon as mild down-titration of iv diuretics was attempted. Levosimendan, a calcium-sensitizer inodilator, indicated for short-term treatment of acutely decompensated severe chronic heart failure (HF), was administered with good clinical response. Thus, we thought that the patient could have benefited from contractility modulation therapy (CCM) which acts on intramyocardial calcium handling. CCM is a novel therapeutic option for patients with classes III–IV HF with EF ≥ 25% to ≤ 45% and narrow QRS complex that acts on intramyocardial calcium-handling. CCM proved effective in alleviating symptoms, improving exercise tolerance and quality of life, and reducing hospitalization rates in HF. It improves myocardial contractility, reverses the foetal myocyte gene program associated with HF and facilitates cardiac reverse remodelling. Therefore, an Optimizer Smart System (Impulse Dynamics) was implanted. Two pacing electrodes were placed on the interventricular septum in apical and mid-septal position, respectively. The leads were connected to a pulse-generator in a right pectoral pocket. In the following days, we observed a progressive improvement in clinical status, with gradual resolution of peripheral oedema, dyspnoea and fatigue and significant weight loss. Six-month echocardiography showed a stable value of EF and significant improvement in stroke volume (35.2 ml from 24.8 ml at baseline). The patient did not undergo further hospitalization for decompensated HF and was in stable ambulatory NYHA Class IV. We believe CCM is an option in patients with advanced HF in which avoiding recurrent hospitalizations, with their overt increase mortality, is often a challenging therapeutic goal. 765 Figure