Arianna Di Molfetta

Left ventricular pacing with a new quadripolar transvenous lead for CRT: Early results of a prospective comparison with conventional implant outcomes

BACKGROUND Flexible left ventricular (LV) pacing configurations are a useful component of cardiac resynchronization therapy (CRT) systems for preventing high LV pacing thresholds and phrenic nerve stimulation (PNS). A quadripolar LV lead has recently been designed with the purpose of allowing more choices in lead placement location and programming capability. OBJECTIVE To verify the effectiveness of quadripolar LV leads compared to conventional bipolar LV leads implant outcomes. METHODS Forty-five consecutive patients underwent implantation with either the quadripolar (n = 22; quadripolar group) or a conventional bipolar LV lead (n = 23; bipolar group). The primary outcome of the study was LV lead failure, defined as the need for lead revision or reprogramming during the first 3 months after implantation. Additionally, operative and follow-up data were prospectively noted and checked for significance between groups. RESULTS The implantation success rate in both groups was 100%. Baseline characteristics, procedure duration, and fluoroscopy time did not differ significantly between groups. Two lead dislodgments (requiring reoperation) and 4 clinical PNS were reported in the bipolar group; reprogramming of the device was sufficient to prevent PNS in 3 patients, the fourth is pending solution. One PNS successfully managed noninvasively occurred in the quadripolar group. By Kaplan-Meier analysis, event-free survival for the combined primary outcome was significantly lower in patients with quadripolar leads (P = .037). CONCLUSION This prospective, controlled study provides strong evidence that CRT with the quadripolar LV lead results in low rates of dislocations and phrenic nerve stimulation.

A modular computational circulatory model applicable to VAD testing and training.

Aim of this work was to develop a modular computational model able to interact with ventricular assist devices (VAD) for research and educational applications. The lumped parameter model consists of five functional modules (left and right ventricles, systemic, pulmonary, and coronary circulation) that are easily replaceable if necessary. The possibility of interacting with VADs is achieved via interfaces acting as impedance transformers. This last feature was tested using an electrical VAD model. Tests were aimed at demonstrating the possibilities and verifying the behavior of interfaces when testing VADs connected in different ways to the circulatory system. For these reasons, experiments were performed in a purely numerical mode, simulating a caval occlusion, and with the model interfaced to an external left-VAD (LVAD) in two different ways: with atrioaortic and ventriculoaortic connection. The caval occlusion caused the leftward shift of the LV p–v loop, along with the drop in arterial and ventricular pressures. A narrower LV p–v loop and cardiac output and aortic pressure rise were the main effects of atrioaortic assistance. A wider LV p–v loop and a ventricular average volume drop were the main effects of ventricular-aortic assistance. Results coincided with clinical and experimental data attainable in the literature. The model will be a component of a hydronumerical model designed to be connected to different types of VADs. It will be completed with autonomic features, including the baroreflex and a more detailed coronary circulation model.

Reproduction of Continuous Flow Left Ventricular Assist Device Experimental Data by Means of a Hybrid Cardiovascular Model With Baroreflex Control

Long-term mechanical circulatory assistance opened new problems in ventricular assist device-patient interaction, especially in relation to autonomic controls. Modeling studies, based on adequate models, could be a feasible approach of investigation. The aim of this work is the exploitation of a hybrid (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo experimental data acquired during a continuous flow left ventricular assistance. The hybrid cardiovascular simulator embeds three submodels: a computational cardiovascular submodel, a computational baroreflex submodel, and a hydronumerical interface submodel. The last one comprises two impedance transformers playing the role of physical interfaces able to provide a hydraulic connection with specific cardiovascular sites (in this article, the left atrium and the ascending/descending aorta). The impedance transformers are used to connect a continuous flow pump for partial left ventricular support (Synergy Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular simulator. Data collected from five animals in physiological, pathological, and assisted conditions were reproduced using the hybrid cardiovascular simulator. All parameters useful to characterize and tune the hybrid cardiovascular simulator to a specific hemodynamic condition were extracted from experimental data. Results show that the simulator is able to reproduce animal-specific hemodynamic status both in physiological and pathological conditions, to reproduce cardiovascular left ventricular assist device (LVAD) interaction and the progressive unloading of the left ventricle for different pump speeds, and to investigate the effects of the LVAD on baroreflex activity. Results in chronic heart failure conditions show that an increment of LVAD speed from 20 000 to 22 000 rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3 L/min). Thanks to its flexibility and modular structure, the simulator is a platform potentially useful to test different assist devices, thus providing clinicians additional information about LVAD therapy strategy.

Impact of continuous intracardiac ST-segment monitoring on mid-term outcomes of ICD-implanted patients with coronary artery disease. Early results of a prospective comparison with conventional ICD outcomes

Background Although myocardial ischaemia monitored by some implantable cardioverter-defibrillators (ICDs) might improve patient care, the clinical usefulness of this technology has not yet been validated. Objective To investigate the potential impact of ICD-based ischaemia monitoring on clinical care and patient management of ICD recipients. Design Prospective, controlled, non-randomised study. Setting Single-centre, university hospital. Patients Consecutive patients with known coronary artery disease, followed up for at least 6 months. Interventions Patients implanted with either an ICD providing continuous intracardiac ST monitoring (n=53; ST group) or with an ICD without this capability (n=50). Main outcome measures Major cardiovascular events, appropriateness of ST-shift episodes and unscheduled device-related visits. Results During follow-up (15.4±8.4 months), one patient experienced ST-shift events confirmed by angiography to be related to myocardial ischaemia. Myocardial infarction was a rare event and occurred in one patient (ST group) who had an ST-elevation myocardial infarction 3 weeks after the implant, but at this time the algorithm had not yet been activated. In the ST group, seven patients had one or more episodes of false-positive ST events (median 9, range 1–90). The programmable features of the device helped overcome the problem in six patients. Among patients with a remote monitoring system, unscheduled outpatient visits were significantly increased in the ST group (17 vs 4; p=0.032). Conclusions Although, this study was underpowered by the small number of acute ischaemic events, ICD-based ST monitoring failed to provide a benefit over ICDs without this capability and increased unscheduled evaluations in patients with remote follow-up. The sensitivity and specificity of the algorithm still require validation.

Simulation of apical and atrio-aortic VAD in patients with transposition or congenitally corrected transposition of the great arteries

Purpose VADs could be used for transportation of the great arteries (TGA) and for congenitally corrected transposition (ccTGA) treatment. A cardiovascular numerical model (NM) may offer a useful clinical support in these complex physiopathologies. This work aims at developing and preliminarily verifying a NM of ccTGA and TGA interacting with VADs. Methods Hemodynamic data were collected at the baseline (BL) and three months (FUP) after apical (atrio-aortic) VAD implantation in a TGA (ccTGA) patient and used in a lumped parameter NM to simulate the patients physiopathology. Measured (MS) and simulated (SIM) data were compared. Results MS and SIM data are in accordance at the BL and at FUP. Cardiac output (l/min): BL_m = 2.9 ± 0.4, BL_s = 3.0 ± 0.3; FUP_m = 4.2 ± 0.2, FUP_s = 4.1 ± 0.1. Right atrial pressure (mmHg): BL_m = 21.4 ± 4.1, BL_s = 18.5 ± 4.5; FUP_m = 13 ± 4, FUP_s = 14.8 ± 3.6. Pulmonary arterial pressure (mmHg): BL_m = 56 ± 6.3, BL_s = 57 ± 2, FUP_m = 37.5 ± 7.5, FUP_s = 35.5 ± 5.9. Systemic arterial pressure (mmHg): BL_m = 71 ± 2, BL_s = 74.6 ± 2.1; FUP_m = 84 ± 9, FUP_s = 81.9 ± 9.8. Conclusions NM can simulate the effect of a VAD in complex physiopathologies, with the inclusion of changes in circulatory parameters during the acute phase and at FUP. The simulation of differently assisted physiopathologies offers a useful support for clinicians.

Hybrid model analysis of intra-aortic balloon pump performance as a function of ventricular and circulatory parameters.

We investigated the effects of the intra-aortic balloon pump (IABP) on endocardial viability ratio (EVR), cardiac output (CO), end-systolic (V(es)) and end-diastolic (V(ed)) ventricular volumes, total coronary blood flow (TCBF), and ventricular energetics (external work [EW], pressure-volume area [PVA]) under different ventricular (E(max) and diastolic stiffness) and circulatory (arterial compliance) parameters. We derived a hybrid model from a computational model, which is based on merging computational and hydraulic submodels. The lumped parameter computational submodel consists of left and right hearts and systemic, pulmonary, and coronary circulations. The hydraulic submodel includes part of the systemic arterial circulation, essentially a silicone rubber tube representing the aorta, which contains a 40-mL IAB. EVR, CO, V(es), and V(ed), TCBF and ventricular energetics (EW, PVA) were analyzed against the ranges of left ventricular E(max) (0.3-0.5-1 mm Hg/cm(3)) and diastolic stiffness V(stiffness) (≈0.08 and ≈0.3 mm Hg/cm(3), obtained by changing diastolic stiffness constant) and systemic arterial compliance (1.8-2.5 cm(3)/mm Hg). All experiments were performed comparing the selected variables before and during IABP assistance. Increasing E(maxl) from 0.5 to 2 mm Hg/cm(3) resulted in IABP assistance producing lower percentage changes in the selected variables. The changes in ventricular diastolic stiffness strongly influence both absolute value of EVR and its variations during IABP (71 and 65% for lower and higher arterial compliance, respectively). V(ed) and V(es) changes are rather small but higher for lower E(max) and higher V(stiffness). Lower E(max) and higher V(stiffness) resulted in higher TCBF and CO during IABP assistance (∼35 and 10%, respectively). The use of this hybrid model allows for testing real devices in realistic, stable, and repeatable circulatory conditions. Specifically, the presented results show that IABP performance is dependent, at least in part, on left ventricular filling, ejection characteristics, and arterial compliance. It is possible in this way to simulate patient-specific conditions and predict the IABP performance at different values of the circulatory or ventricular parameters. Further work is required to study the conditions for heart recovery modeling, baroreceptor controls, and physiological feedbacks.

Device monitoring of heart failure in cardiac resynchronization therapy device recipients: a single-center experience with a novel multivector impedance monitoring system.

Objectives We investigated the performance of a new intrathoracic multivector impedance monitoring system for the prediction of heart failure events in consecutive device-implanted patients. Methods Eighty heart failure patients implanted with biventricular defibrillators with multivector impedance monitoring capability were prospectively enrolled. Clinical heart failure status and impedance data were assessed during follow-up and if patients presented with an alert or heart failure deterioration. Results During follow-up (8.0 ± 4.4 months), 56 events of device alert for fluid index increase were identified in 29 patients, and a total of 39 heart failure events (defined by worsening of heart failure signs and symptoms) occurred in 23 patients. The sensitivity and positive predictive value (PPV) for heart failure deterioration was 61.5 and 42.9%, respectively. False-positive alerts occurred in 23 of 80 patients (28.8%), for an episode rate of 0.60 a year. Among all clinical heart failure events, decompensation caused hospitalization in 13 cases (33.3%), seven of them were preceded by an alert condition (53.8%) resulting in a sensitivity of 53.8% and a PPV of 17.9%. Conclusion The present study confirms the feasibility and clinical usefulness of this novel multivector impedance monitoring system. It would be worthwhile to perform larger studies to assess its actual clinical value in heart failure patients.

A Model of the Cardiorespiratory Response to Aerobic Exercise in Healthy and Heart Failure Conditions.

The physiological response to physical exercise is now recognized as an important tool which can aid the diagnosis and treatment of cardiovascular diseases. This is due to the fact that several mechanisms are needed to accommodate a higher cardiac output and a higher oxygen delivery to tissues. The aim of the present work is to provide a fully closed loop cardiorespiratory simulator reproducing the main physiological mechanisms which arise during aerobic exercise. The simulator also provides a representation of the impairments of these mechanisms in heart failure condition and their effect on limiting exercise capacity. The simulator consists of a cardiovascular model including the left and right heart, pulmonary and systemic circulations. This latter is split into exercising and non-exercising regions and is controlled by the baroreflex and metabolic mechanisms. In addition, the simulator includes a respiratory model reproducing the gas exchange in lungs and tissues, the ventilation control and the effects of its mechanics on the cardiovascular system. The simulator was tested and compared to the data in the literature at three different workloads whilst cycling (25, 49 and 73 watts). The results show that the simulator is able to reproduce the response to exercise in terms of: heart rate (from 67 to 134 bpm), cardiac output (from 5.3 to 10.2 l/min), leg blood flow (from 0.7 to 3.0 l/min), peripheral resistance (from 0.9 to 0.5 mmHg/(cm3/s)), central arteriovenous oxygen difference (from 4.5 to 10.8 ml/dl) and ventilation (6.1–25.5 l/min). The simulator was further adapted to reproduce the main impairments observed in heart failure condition, such as reduced sensitivity of baroreflex and metabolic controls, lower perfusion to the exercising regions (from 0.6 to 1.4 l/min) and hyperventilation (from 9.2 to 40.2 l/min). The simulator we developed is a useful tool for the description of the basic physiological mechanisms operating during exercise. It can reproduce how these mechanisms interact and how their impairments could limit exercise performance in heart failure condition. The simulator can thus be used in the future as a test bench for different therapeutic strategies aimed at improving exercise performance in cardiopathic subjects.

A modeling tool to study the combined effects of drug administration and LVAD assistance in pathophysiological circulatory conditions

The aim of this work is to develop a tool to study the effect of sodium nitroprusside (SNP) on hemodynamics in conjunction with baroreflex and mechanical circulatory assistance. To this aim, a numerical model of the pharmacodynamic effect of SNP was developed and inserted into a cardiovascular circulatory model integrated with baroreflex and LVAD (continuous flow pump with atrio-aortic connection) sub-models. The experiments were carried out in two steps. In the first step the model was verified comparing simulations with experimental data acquired from mongrel dogs on mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), peripheral resistance, and left ventricular properties. In the second step, the combined action of SNP and mechanical circulatory assistance was studied. Data were measured at pump off and at pump on (20000 rpm and 24000 rpm). At pump off, with a 2.5 μg/kg per min SNP infusion in heart failure condition, the MAP was reduced by approximately 8%, CO and HR increased by about 16% and 18%, respectively. In contrast, during assistance (24000 rpm) the changes in MAP, CO and HR were around −9%, +12%, and +20%, respectively. Furthermore, the effects of the drug on hemodynamic parameters at different heart conditions were significantly different. Thus, the model provides insight into the complex interactions between baroreflex, drug infusion, and LVAD and could be a support for clinical decision-making in cardiovascular pathologies.

Berlin Heart EXCOR Ventricular Assist Device: Multilayer Membrane Rupture in a Pediatric Patient

A 2-year-old child was implanted with an Berlin Heart EXCOR Ventricular Assist Device (Berlin Heart, Berlin, Germany) as a bridge to heart transplantation for idiopathic dilated cardiomyopathy. At postoperative day 296, a significant reduction of membrane movement was observed. The device was explanted and tested on a hydronumerical circulation simulator. Findings suggested that the integrity of the multilayered membrane had been compromised. This was confirmed by a computed tomography scan of the device. The computed tomography evidenced a detachment of the 3-layered membrane, with a thinner, convex layer on the side of the air chamber and an opposite convexity of the remaining membranes. These showed an additional air space within the layers.