Gabriele Dell’Era

Mean platelet volume and the extent of coronary artery disease: Results from a large prospective study

BACKGROUND Platelets play a central role in the pathogenesis of coronary artery disease. Mean platelet volume (MPV) is an indicator of platelet activation, and has been demonstrated to be correlated with platelet reactivity. The aim of the current study was to investigate whether mean platelet volume is associated with the extent of coronary artery disease. METHODS We measured MPV in 1411 consecutive patients undergoing coronary angiography. All angiograms were analyzed by two investigators blinded of clinical data. Significant coronary artery disease was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. The relationship between MPV and platelet aggregation was evaluated by PFA-100 in 50 consecutive patients who were not taken any antiplatelet therapy, and in a cohort of patients who were on aspirin by PFA-100 (n=161) and Multiplate (n=94). RESULTS Patients were divided into three groups according to tertiles of MPV. Patients with higher MPV were slightly older (p=0.038), with larger prevalence of diabetes (p<0.0001), hypertension (p=0.008), previous CVA (p=0.041), less often with stable angina (p=0.043) and family history of CAD (p=0.011), more often on statins (p=0.012), and diuretics (p=0.007). MPV was associated with baseline glycaemia (p<0.0001) and red blood cell count (p=0.056), but inversely related to platelet count (p<0.0001). MPV was not associated with the extent coronary artery disease (p=0.71) and carotid IMT (p=0.9). No relationship was found between MPV and platelet aggregation. CONCLUSION This study showed that MPV is not related to platelet aggregation, the extent of coronary artery disease and carotid IMT. Thus, this parameter cannot be considered as a marker of platelet reactivity or a risk factor for coronary artery disease.

Long-term follow-up of DDDR closed-loop cardiac pacing for the prevention of recurrent vasovagal syncope.

Aims Vasovagal syncope (VVS) is a common disorder characterized by a drop in blood pressure accompanied with bradycardia; although it is generally considered a benign condition, some patients may be highly symptomatic despite general counselling and/or pharmacological therapy. Closed-loop stimulation (CLS), responding to myocardial contraction dynamics, demonstrated effectiveness in short-term prevention of recurrent VVS. The aim of this study was to evaluate CLS pacing in a long-term follow-up. Methods The study involved 35 patients (mean age 59 ± 15 years) with 3 years’ follow-up (mean 61 ± 35 months). We compared syncopal events and presyncopes before and after CLS implantation. Mean number of syncopes for patients was six (range 1–24; 212 syncopal spells registered) before pacemaker implantation. Results At follow-up, 29 of 35 patients (83%) were asymptomatic; one patient experienced recurrent loss of consciousness but reported an improvement in the quality of life (one syncope or presyncope per month after CLS, vs. one syncope per week and daily presyncopes before CLS). Five patients experienced syncopal recurrences after CLS (range: 1–7, with a total of 15 episodes); in all the cases, the number of post-CLS syncopes was significantly lower. Conclusion Our study seems to confirm previous results of short-term trials: DDDR-CLS pacing is an extremely useful tool in the prevention of recurring VVS, even in long-term follow-up.

Effects of closed-loop stimulation vs. DDD pacing on haemodynamic variations and occurrence of syncope induced by head-up tilt test in older patients with refractory cardioinhibitory vasovagal syncope: the Tilt test-Induced REsponse in Closed-loop Stimulation multicentre, prospective, single blind, randomized study

Aims Closed-loop stimulation (CLS) seemed promising in preventing the recurrence of vasovagal syncope (VVS) in patients with a cardioinhibitory response to head-up tilt test (HUTT) compared with conventional pacing. We hypothesized that the better results of this algorithm are due to its quick reaction in high-rate pacing delivered in the early phase of vasovagal reflex, which increase the cardiac output and the blood pressure preventing loss of consciousness. Methods and results This prospective, randomized, single-blind, multicentre study was designed as an intra-patient comparison and enrolled 30 patients (age 62.2 ± 13.5 years, males 60.0%) with cardioinhibitory VVS, carrying a dual-chamber pacemaker incorporating CLS algorithm. Two HUTTs were performed one week apart: one during DDD-CLS 60-130/min pacing and the other during DDD 60/min pacing; patients were randomly and blindly assigned to two groups: in one the first HUTT was performed in DDD-CLS (n = 15), in the other in DDD (n = 15). Occurrence of syncope and haemodynamic variations induced by HUTT was recorded during the tests. Compared with DDD, DDD-CLS significantly reduced the occurrence of syncope induced by HUTT (30.0% vs. 76.7%; P < 0.001). In the patients who had syncope in both DDD and DDD-CLS mode, DDD-CLS significantly delayed the onset of syncope during HUTT (from 20.8 ± 3.9 to 24.8 ± 0.9 min; P = 0.032). The maximum fall in systolic blood pressure recorded during HUTT was significantly lower in DDD-CLS compared with DDD (43.2 ± 30.3 vs. 65.1 ± 25.8 mmHg; P = 0.004). Conclusion In patients with cardioinhibitory VVS, CLS reduces the occurrence of syncope induced by HUTT, compared with DDD pacing. When CLS is not able to abort the vasovagal reflex, it seems to delay the onset of syncope.

Prevalence of ventricular arrhythmias in patients with cardiac resynchronization therapy without back-up ICD: a single-center experience.

Aims Current guidelines recommend cardiac resynchronization therapy (CRT) in selected heart failure patients, but do not precisely clarify when a back-up implantable cardioverter defibrillator (ICD) should be associated (CRT-D). In this study we evaluate the occurrence of ventricular arrhythmias in a population of patients implanted with biventricular pacemaker without a back-up ICD (CRT-P). Methods We performed a retrospective analysis on 84 patients (55 men, mean age 74 ± 7 years), implanted with a CRT-P since April 2000. Patients had in 31% an underlying coronary artery disease, in 56% an idiopatic dilated cardiomyopathy and in 13% a valvular disease. An upgrade to CRT-P was performed from previous conventional pacemakers in 36% of cases. Baseline New York Heart Association (NYHA) functional class was II in 25%, III in 63% and IV in 12%. Mean left ventricular ejection fraction was 29.8 ± 8.8% with two-dimensional echo. During follow-up, occurrence of ventricular arrhythmias was assessed clinically and through the pacemaker stored data at the scheduled check-up. Results During a mean follow-up of 29 months (range 2–127 months), telemetry interrogation revealed unsustained ventricular tachyarrhythmias in 11 of 84 patients (13.1%). Only one patient experienced an episode of sustained ventricular tachycardia. An upgrading to a CRT-D was performed in two patients; one of these patients died suddenly 15 months after the upgrade. Death occurred in 20 of 84 patients (23.8%): 15 for refractory heart failure and five for noncardiac causes. Conclusion Our data show that CRT-P may be well tolerated in selected patients even during a long-term follow-up; and that an upgrade to CRT-D may not be enough to prevent sudden death.

Cardiac resynchronization therapy and electrical storm: results of the OBSERVational registry on long-term outcome of ICD patients (OBSERVO-ICD)

Aims Electrical storm (ES) is a condition defined as three or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 h, and usually coexist with advanced heart failure in patients with structural heart disease. The aim of the present study is to test whether cardiac resynchronization therapy (CRT) can be associated with a lower incidence of ES. Methods and results The OBSERVO-ICD (NCT02735811) is a multicentre, retrospective registry, enrolling all consecutive patients undergoing ICD or CRT-D implantation from 2010 to 2012 in five Italian high-volume arrhythmia centres. Propensity score matching was used to compare two equally sized cohorts of ICD and CRT-D patients with similar characteristics. The primary endpoint was the time free from ES. Secondary endpoints were time free from unclustered VT/VF episodes and time free from ES in CRT-D patients according to clinical or echographic response. CRT-D was associated with a 45% relative risk reduction in ES when compared with ICD (5.6% vs. 12.3%; log rank P = 0.014). CRT-responders presented lower rates of ES when compared with non-responders and negative responders according to both clinical and echographic criteria (log-rank P = 0.017 and 0.023, respectively). No ES was detected in any of the 133 full responders to CRT-D. Clinical and echographic positive responses, but not CRT-implant per se, were associated with lower estimate rates of unclustered VTs/VFs. Conclusion Patients with CRT had a lower incidence of ES when compared with propensity-matched ICD patients. The long-term benefit of CRT seems to be due to the improved haemodynamics, as CRT-responders performed markedly better over a long-term follow-up.

Non-invasively estimated left atrial stiffness is associated with short-term recurrence of atrial fibrillation after electrical cardioversion

BACKGROUND As atrial stiffness (Kla) is an important determinant of cardiac pump function, better mechanical characterization of left atrial (LA) cavity would be clinically relevant. Pulmonary venous ablation is an option for atrial fibrillation (AF) treatment that offers a powerful context for improving our understanding of LA mechanical function. We hypothesized that a relation could be detected between invasive estimation of Kla and new non-invasive deformation parameters and traditional LA and left ventricular (LV) function descriptors, so that Kla can be estimated non-invasively. We also hypothesized that a non-invasive surrogate of Kla would be useful in predicting AF recurrence after cardioversion. METHODS In 20 patients undergoing AF ablation, LA pressure-volume curves were derived from invasive pressure and echocardiographic images; Kla was calculated during ascending limb of V-loop as ΔLA pressure/ΔLA volume. 2D-speckle-tracking echocardiographic LA and LV longitudinal strains and volumes, ejection fraction (EF) and ventricular stiffness (Klv), as obtained from mitral deceleration time, were tested as non-invasive Kla predictors. In 128 sinus rhythm patients 1 month after electrical cardioversion for persistent AF, non-invasively estimated Kla (computed-Kla) was tested as predictor of recurrence at 6 months. RESULTS Tertiles of mean LA pressure correlated with increasing Kla (trend, p=0.06) and decreasing LA peak strain, LVEF, and LV longitudinal strain (p=0.029, p=0.019, and p=0.024). There were no differences in LA and LV volumes and Klv across groups. Multiple regression analysis identified LV longitudinal strain as the only independent predictor of Kla (p=0.014). Patients in highest quartile of computed-Kla (estimated as [log]=0.735+0.051×LV strain) tended to have highest AF recurrence rate (25%) as compared with remaining 3 quartiles (9%, 9%, 3%, p=0.09). CONCLUSION Kla can be assessed invasively in patients undergoing AF ablation and it can be estimated non-invasively using LV strain. AF recurrence after cardioversion tends to be highest in highest quartile of computed-Kla.

Persistence of ICD indication at the time of replacement in patients with initial implant for primary prevention indication: Effect on subsequent ICD therapies

Background Indication to implantable cardioverter defibrillator (ICD) for primary prevention of sudden death relies on left ventricular ejection fraction (LVEF). We measured the proportion of patients in whom indication to ICD persisted at the time of generator replacement (GR) and searched for predictors of appropriate therapies after GR. Methods We identified all consecutive patients who had received an ICD at our hospital, for LVEF ≤35% and no previous arrhythmias or unexplained syncope. Then, we included the 166 patients who outlived their first device and underwent GR. Results At the time of GR (mean follow-up 59 ± 20 months), ICD indication (i.e. LVEF ≤35% or previously treated ventricular arrhythmias) persisted in 114 (69%) patients. After GR, appropriate ICD therapies were delivered in 30 (26%) patients with persistent ICD indication and in 12 (23%) of the remaining patients (p = 0.656). Nonetheless, the annual rate of therapies was higher in the first group (1.08 versus 0.53 events/year; p < 0.001), as well as the rate of inappropriate therapies (0.03 versus 0 events/year; p = 0.031). The only independent predictor of appropriate ICD therapies after GR was the rate of shocks received before replacement (Hazard Ratio: 1.41; 95% confidence interval: 1.01–1.96; p = 0.041). Conclusion In heart failure with reduced LVEF, ICD indication persisted at the time of GR in 69% of patients. However, even in the absence of persistent ICD indication at GR, the risk of recurrence of arrhythmic events was not null.

An unusual case of ECG ST-segment elevation.

To the Editor A 76-year-old white woman with hypertension and a history of a mantle cell nonHodgkin lymphoma was admitted to the emergency department with shortness of breath and slight chest pain. Physical examination showed a tachyarrhythmic heart rate (162 beats/min) with normal blood pressure (120/60 mmHg); serial 12-lead electrocardiogram showed evidence of atrial fibrillation with a diffuse ST-segment elevation in the lateral leads (Fig. 1).

IntErnationaL eLeCTRicAl storm registry (ELECTRA): Background, rationale, study design, and expected results

Electrical storm (ES) is defined as three or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 h and is associated with an increased cardiac and all-cause mortality. ES is a full arrhythmic emergency, its prevalence steadily increasing along with the number of implantable cardioverter-defibrillator implanted every year in developed countries. Nowadays, little evidence exists regarding clinical predictors of ES and their potential association on mortality and heart failure (HF), nor optimal pharmacological and non-pharmacological treatment has ever been codified. The intErnationaL eLeCTRicAl storm registry (ELECTRA) is a multicentre, observational, prospective clinical study with two major aims. First, to create an international database on ES encompassing clinical features, pharmacological management, and interventional treatment strategies. Second, to describe mortality and rehospitalization rates in patients with ES over a long follow-up. The primary endpoint is all-cause mortality 3 years after the ES index event. The main secondary endpoint is hospitalization for all causes 3 years after the ES index event. Other secondary endpoints includes ES recurrences, unclustered VTs/VFs recurrences, and hospitalizations for HF worsening. A minimum of 500 patients will be included in the registry, and all patients will be followed-up for a minimum of three years. The present paper describes the background and current rationale of the ELECTRA study and details the study design, from enrolment strategy to data collection methods to planned data analysis. A brief overview of the expected results and their potential clinical and research implications will also be presented (NCT02882139).