Severity of spleep apnea syndrome and life-threatening tachyarrhythmias in patients with implantable cardioverter defibrillator.

BACKGROUND: Sleep apnea syndrome (SAS) has been reported to be associated with a higher incidence of ventricular arrhythmias. The aim of this study was twofold: (1) to investigate whether in SAS patients receiving an implantable cardioverter defibrillator (ICD) the severity of SAS was associated with the occurrence of ventricular arrhythmias; (2) to assess whether changes in nocturnal apnoic/hypopnoic episodes may favor the occurrence of life-threatening arrhythmias, that is, sustained ventricular tachycardia (VT)/fibrillation (VF), requiring ICD intervention. METHODS: We enrolled 46 patients with documented SAS at polysomnography (apnea/hypopnea index [AHI] > 5) who also had a left ventricle ejection fraction (LVEF) < 35% and, according to primary prevention indications, implanted an ICD (Boston Scientific Incepta) able to daily monitor apnoic/hypopnoic episodes occurring during sleep. Patients were followed at 3-month intervals. RESULTS: At a mean follow-up of 18 months, 21 episodes of sustained VT/FV requiring ICD intervention were documented in eight patients (17.4%). Baseline AHI was significantly higher in patients with compared to those without ICD intervention. ICD interventions, however, were not preceded by any worsening of apnoic/hypopnoic episodes. The respiratory disturbance index (RDI) of the week during the event, indeed, was not different from that recorded during the previous 2 weeks (25.4 ± 11, 25.6 ± 10 and 25.1 ± 10, respectively; p = .9). CONCLUSIONS: In patients with SAS who received an ICD for primary prevention of sudden death, those with ICD interventions showed a more severe form of the disease at baseline. ICD interventions, however, were not preceded by any significant changes in SAS severity.

Comparison of six disease severity scores for allergic rhinitis against pollen counts a prospective analysis at population and individual level.

BACKGROUND: Many different symptom (medication) scores are nowadays used as measures of allergic rhinoconjunctivitis severity in individual patients and in clinical trials. Their differences contribute to the heterogeneity of the primary end-point in meta-analyses, so that calls for symptom (medication) score harmonization have been launched. OBJECTIVE: To prospectively compare six different severity scores for allergic rhinitis (AR) against pollen counts at both population and individual levels. METHODS: Two groups of children with seasonal AR and grass pollen sensitization were recruited in Ascoli, Italy (n = 76) and Berlin, Germany (n = 29). Symptoms and drug intake were monitored daily for 40 and 30 days of the grass pollen season in 2011 (Ascoli) and 2013 (Berlin), respectively, through an Internet-based platform (AllergyMonitor(™) , TPS Production srl, Rome, Italy). From the gathered data, the informatics platform automatically generated one symptom score (RTSS) and five symptom-medication scores (RC-ACS(©) , ACS, RTSS[LOCF], RTSS[WC] and AdSS). Values were then statistically normalized for reciprocal comparison and matched against the daily variations of local grass pollen counts (Spearman's rank correlation). RESULTS: The grass pollen counts were higher in Ascoli than in Berlin (peak values 194 vs. 59 grains/m(3) ). At population level, the trajectories of the normalized average values of the six scores differed only slightly in both studies and correlated well with the pollen counts (ranges r(2) : 0.38-0.50 in Ascoli, 0.41-0.56 in Berlin). By contrast, in individual patients, trajectories of different scores were often quite heterogeneous. The RTSS[WC] had a very low discriminatory power and generated in many patients long, flat horizontal segments. CONCLUSIONS: Disease severity scores for seasonal AR, as evaluated via an Internet-based platform, tend to provide similar results at population level but can often produce heterogeneous slopes in individual patients. The choice of the disease severity score might have only a low impact on the outcome of a very large clinical trial, but it may be crucial in the management of individual patients.

Outcome of Patients Treated by Cardiac Resynchronization Therapy Using a Quadripolar Left Ventricular Lead.

BACKGROUND: Not all heart failure (HF) patients benefit from cardiac resynchronization therapy (CRT). We assessed whether choosing the site of left ventricular (LV) pacing by a quadripolar lead may improve response to CRT. METHODS AND RESULTS: We prospectively randomized 23 patients with HF (67±11 years; 21 males) to CRT with a quadripolar LV lead (group 1, with the LV pacing site chosen on the basis of QRS shortening using simultaneous biventricular pacing), and 20 patients (71±6 years; 16 males) to a bipolar LV lead (group 2, with devices programmed with a conventional tip-to-ring configuration). New York Heart Association (NYHA) class and LV ejection fraction (EF) by 2D echocardiography were assessed at baseline and after 3 months. The baseline EF was not different between the 2 groups (25±6% group 1 vs. 27±3% group 2; P=0.22), but after 3 months EF was higher in group 1 (35±13% group 1 vs. 31±4% group 2; P<0.001). A reduction in at least 1 NYHA class at 3 months was observed in 22 (96%) and 12 (60%) of group 1 and group 2 patients, respectively (P<0.05). CONCLUSIONS: CRT with a quadripolar LV lead was associated with an improvement of EF greater than that observed in patients receiving a bipolar LV lead. In devices with a quadripolar lead, CRT programming based on the best QRS shortening is reliable and effective. (Circ J 2016; 80: 613-618).

The association between ICD interventions and mortality is independent of their modality: clinical implications.

BACKGROUND: Patients with severe structural heart disease have increased mortality after implantable cardioverter-defibrillator (ICD) shocks. Whether this is limited to ICD shock therapy only or extends also to no-shock therapies, such as antitachycardia pacing (ATP), is unclear. We investigated the impact of different ICD therapies on long-term mortality. METHODS: We enrolled 573 patients who underwent ICD implantation at our institution from 2004 to 2011. The population was divided into 3 groups: no device interventions (group 1), ATP interventions (group 2), and shock interventions (group 3). The endpoint was the all-cause mortality. RESULTS: Over a follow-up period of 48 months (range 1-110), 447 (78%) had no device interventions, 71 (12%) had ATP therapy only, and 55 (10%) had at least one shock intervention. All-cause mortality occurred in 94 patients in group 1 (21%), 23 patients (43%) in group 2, and 21 patients (38%) in group 3. At multivariable Cox regression analysis, ATP intervention (HR: 1.8; 95% CI 1.1-3; P < 0.001), shock intervention (HR: 1.39; 95% CI 1.09-1.77; P = 0.008), age (HR: 1.05; 95% CI 1.02-1.07; P < 0.001), and LVEF (HR: 0.95; 95% CI 0.93-0.98; P = 0.001) were predictors of all-cause mortality. No significant difference in mortality was found between group 2 and 3. CONCLUSION: Patients with ICDs who receive appropriate interventions are at increased risk of mortality. Such risk is not dependent on different types of ICD therapy, such as shocks or ATP. Our data suggest that sustained ventricular arrhythmias per se have a negative impact on prognosis rather than modality of ICD therapy.

[Cardiac contractility modulation: a treatment option for patients with refractory heart failure]. / La modulazione della contrattilità cardiaca: un'opzione terapeutica per il paziente con insufficienza cardiaca refrattaria.

Heart failure is the cardiovascular epidemic of the 21st century, with poor prognosis and quality of life despite optimized medical treatment. In the past two decades, only two new drugs have been added to therapeutic strategies for patients with symptomatic heart failure and even less progresses have been made on devices, with the implantable defibrillator indicated for patients with ejection fraction ≤35% and cardiac resynchronization therapy for those with QRS >130 ms and evidence of left bundle branch block. Nevertheless, only a third of patients meet these criteria and a high percentage of patients are non-responders in terms of improving symptoms. Nowadays, in patients with symptomatic heart failure with ejection fraction between 25% and 45% and QRS <130 ms, not eligible for cardiac resynchronization therapy, cardiac contractility modulation represents a concrete treatment option, having proved to be safe and effective in reducing hospitalizations for heart failure and improving symptoms, functional capacity and quality of life.The aim of this review is therefore to summarize the pathophysiological mechanisms, the current indications and the recent developments regarding the new applications of cardiac contractility modulation for patients with chronic heart failure.

Renal artery stenting in patients with chronic ischemic heart disease.

OBJECTIVES: To investigate the role of renal stenting in selected patients with chronic ischemic heart disease and renal artery stenosis. METHODS: Consecutive patients, with chronic ischemic heart disease and severe hypertension and/or impaired renal function undergoing renal stenting, were prospectively enrolled. Mid-term (at least 2 years) follow-up was performed to assess both changes in renal function [serum creatinine and estimated glomerular filtrate rate (eGFR)] and blood pressure (BP) control (number of required drugs) and to record the incidence of clinical major adverse events. Moreover, in the first consecutive 24 patients, out-of-range pressure values at 24-hr BP monitoring and GFR at renal scintigraphy were measured at baseline and 1 month after stenting. RESULTS: Seventy patients treated by stenting on 86 renal arteries entered the study. Procedural success rate was 99% and no major complication occurred. At 2-year follow-up, both mean serum creatinine (-0.1 +/- 0.7 mg/dl at follow-up compared to baseline, P = 0.6) and eGFR (+3.7 +/- 23.5 ml/min/1.73m(2) at follow-up compared to baseline, P = 0.2) did not significantly change while the number of drugs required to control BP significantly decreased (2.7 +/- 0.8 to 2.2 +/- 0.7, P < 0.0001). In the subset of 24 patients evaluated at 1 month, GFR significantly increased (62 +/- 20 ml/min to 67 +/- 21 ml/min; P = 0.008) and the rate of the out-of-range systolic pressure values at 24-hr monitoring significantly decreased (51-33%, P = 0.005). Elevated baseline creatinine values and the presence of global renal ischemia were identified as predictors of poor outcome at the multivariate analysis. CONCLUSIONS: In selected patients with chronic ischemic heart disease and hypertension and/or renal insufficiency, renal stenting may be performed with very low periprocedural complications and results in unchanged renal function and improved BP control.

Influence of left ventricular hypertrophy on microvascular dysfunction and left ventricular remodelling after acute myocardial infarction.

AIMS: To ascertain whether the presence of left ventricular (LV) hypertrophy in patients with ST-segment elevation myocardial infarction (STEMI) influences microvascular dysfunction and LV remodelling at 6 months of follow-up. METHODS AND RESULTS: Fifty-six consecutive STEMI patients successfully treated with primary or rescue percutaneous coronary intervention underwent conventional two-dimensional and myocardial contrast echocardiography within 24 h and at 6 months. Left ventricular mass, end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction, and wall motion score index (WMSI) were measured. Left ventricular hypertrophy was defined as LV mass index >116 g/m(2) in men and >104 g/m(2) in women. In order to evaluate the potential influence of microvascular dysfunction on LV remodelling, myocardial perfusion was semiquantitatively scored by contrast score index (CSI). Patients with LV hypertrophy had higher EDV and ESV both at 24 h and at 6 months, compared with patients without LV hypertrophy (P < 0.05). No significant changes over time were observed in both groups. Both WMSI and CSI were similar between groups at 24 h and at follow-up, but improved in both groups over time (P < 0.05). CONCLUSION: Left ventricular hypertrophy does not appear to influence the development of post-acute myocardial infarction LV remodelling. Hypertrophic and non-hypertrophic left ventricles showed the same extent and temporal improvement in regional contractile function and microvascular perfusion.

Prognostic significance of non-sustained ventricular tachycardia on stored electrograms in pacemaker recipients.

BACKGROUND: Little is known about the prognostic significance of non-sustained ventricular tachycardia (NS-VT) in outpatients scheduled for routine pacemaker controls. We therefore sought to investigate the prognostic significance of non-sustained ventricular tachycardia on stored electrograms in pacemaker recipients. METHODS: We enrolled patients implanted with dual chamber pacemaker for atrioventricular block or sinus node dysfunction from 2010 to 2016, with LVEF> 45%, older than 18 years, with at least 3 device interrogations at follow-up. Data were collected about medical history, pharmacological therapy at implantation, pacemaker programming, NS-VT occurrence, long-term survival. RESULTS: A total of 308 patients were included in the final analysis, with median follow-up time of 56 months. No ventricular arrhythmic episodes were documented in 221 patients (Group 1), whereas 87 had at least 1 episode of NS-VT during follow-up (Group 2). As a whole, 282 episodes of NS-VT were documented. There was a higher prevalence of previous myocardial infarction and slightly lower left ventricular ejection fraction (LVEF) in Group 2. The primary endpoint (all-cause mortality) occurred in 50 patients (22%) of Group 1 and 12 (14%) patients of Group 2 (p = 0.07). Clinical predictors of all-cause mortality at univariate analysis included age, LVEF and coronary artery disease (CAD). Only age and CAD, however, remained as predictors of mortality at multivariable analysis. A sizeable, but not statistically significant, portion of patients who died had a de novo occurrence of NS-VT at the last pacemaker check. CONCLUSION: Our data do not support a prognostic role for the detection of NS-VT during pacemaker controls.

Cardiac troponin T and NT-proBNP as diagnostic and prognostic biomarkers of primary cardiac involvement and disease severity in systemic sclerosis: A prospective study.

OBJECTIVES: The aim of our study was to define the role of high-sensitive cardiac troponin T (hs-cTnT) and NT-proBNP in identifying Systemic Sclerosis (SSc) patients with cardiac involvement and at higher risk of cardiac death. METHODS: Plasma hs-cTnT and NT-proBNP concentrations were measured in 245 SSc-patients. RESULTS: hs-cTnT and NT-proBNP levels were higher in SSc-patients than in healthy controls. Hs-cTnT levels were higher than 0.014 ng/ml in 32.3% SSc-patients, while NT-proBNP was above 125 pg/ml in 31.8% of them, irrespective of classical cardiovascular risk factor and of pulmonary arterial hypertension. Elevated hs-cTnT and NT-proBNP were associated with diffuse skin involvement and directly correlated with the skin score. Patients with increased cardiac markers presented a lower left-ventricular ejection fraction (LVEF) and a higher rate of right bundle branch block (RBBB) on electrocardiogram (ECG) compared to patients with normal cardiac enzymes. During the follow-up, 12 SSc-patients experience a disease-related death; 9 of these were directly related to cardiac involvement (sudden cardiac death or heart failure) and the majority of them occurred among patients with increase of at least one cardiac biomarker. Long-term survival was worse in patients with increase of both cardiac biomarkers. CONCLUSIONS: Evaluation of hs-cTnT and NT-proBNP levels may provide a tool to screen non-invasively SSc-patients for heart involvement. A higher incidence of impaired systolic function, ECG abnormalities and a poor outcome in SSc-patients with elevated cardiac enzymes suggests that they may be valuable screening biomarkers to detect a cardiac damage at early stages and to improve risk stratification.

DNA metabarcoding uncovers fungal diversity of mixed airborne samples in Italy.

Fungal spores and mycelium fragments are particles which become and remain airborne and have been subjects of aerobiological studies. The presence and the abundance of taxa in aerobiological samples can be very variable and impaired by changeable climatic conditions. Because many fungi produce mycotoxins and both their mycelium fragments and spores are potential allergens, monitoring the presence of these taxa is of key importance. So far data on exposure and sensitization to fungal allergens are mainly based on the assessment of few, easily identifiable taxa and focused only on certain environments. The microscopic method used to analyze aerobiological samples and the inconspicuous fungal characters do not allow a in depth taxonomical identification. Here, we present a first assessment of fungal diversity from airborne samples using a DNA metabarcoding analysis. The nuclear ITS2 region was selected as barcode to catch fungal diversity in mixed airborne samples gathered during two weeks in four sites of North-Eastern and Central Italy. We assessed the taxonomic composition and diversity within and among the sampled sites and compared the molecular data with those obtained by traditional microscopy. The molecular analyses provide a tenfold more comprehensive determination of the taxa than the traditional morphological inspections. Our results prove that the metabarcoding analysis is a promising approach to increases quality and sensitivity of the aerobiological monitoring. The laboratory and bioinformatic workflow implemented here is now suitable for routine, high-throughput, regional analyses of airborne fungi.

Myocardial infarction in isolated ventricular non-compaction: contrast echo and MRI.

We describe the case of an occasional discovery of isolated ventricular non-compaction in an adult recovered for an acute myocardial infarction, in which only the echocardiogram revealed an isolated ventricular non-compaction, confirmed by MRI: an unusual association between coronary artery disease and isolated ventricular non-compaction.

Prognostic Role of Ventricular Ectopic Beats in Systemic Sclerosis: A Prospective Cohort Study Shows ECG Indexes Predicting the Worse Outcome.

BACKGROUND: Arrhythmias are frequent in Systemic Sclerosis (SSc) and portend a bad prognosis, accounting alone for 6% of total deaths. Many of these patients die suddenly, thus prevention and intensified risk-stratification represent unmet medical needs. The major goal of this study was the definition of ECG indexes of poor prognosis. METHODS: We performed a prospective cohort study to define the role of 24h-ECG-Holter as an additional risk-stratification technique in the identification of SSc-patients at high risk of life-threatening arrhythmias and sudden cardiac death (SCD). One-hundred SSc-patients with symptoms and/or signs suggestive of cardiac involvement underwent 24h-ECG-Holter. The primary end-point was a composite of SCD or need for implantable cardioverter defibrillator (ICD). RESULTS: Fifty-six patients (56%) had 24h-ECG-Holter abnormalities and 24(24%) presented frequent ventricular ectopic beats (VEBs). The number of VEBs correlated with high-sensitive cardiac troponin T (hs-cTnT) levels and inversely correlated with left-ventricular ejection fraction (LV-EF) on echocardiography. During a mean follow-up of 23.1±16.0 months, 5 patients died suddenly and two required ICD-implantation. The 7 patients who met the composite end-point had a higher number of VEBs, higher levels of hs-cTnT and NT-proBNP and lower LV-EF (p = 0.001 for all correlations). All these 7 patients had frequent VEBs, while LV-EF was not reduced in all and its range was wide. At ROC curve, VEBs>1190/24h showed 100% of sensitivity and 83% of specificity to predict the primary end-point (AUROC = 0.92,p<0.0001). Patients with VEBS>1190/24h had lower LV-EF and higher hs-cTnT levels and, at multivariate analysis, the presence of increased hs-cTnT and of right bundle branch block on ECG emerged as independent predictors of VEBs>1190/24h. None of demographic or disease-related characteristics emerged as predictors of poor outcome. CONCLUSIONS: VEBS>1190/24h identify patients at high risk of life-threatening arrhythmic complications. Thus, 24h-ECG-Holter should be considered a useful additional risk-stratification test to select SSc-patients at high-risk of SCD, in whom an ICD-implantation could represent a potential life-saving intervention.

Use of a novel high-osmolar gadolinium chelate, gadobutrol, for percutaneous renal artery stenting in two patients with chronic renal failure.

Gadolinium chelates have been recently proposed and preliminarily tested as contrast agents for diagnostic and interventional angiography in alternative to iodinated media. However, in most studies low-osmolarity agents were employed and digital subtraction was required for satisfactory images. In this article, we report for the first time in the literature two cases of successful percutaneous renal artery stenting in which gadobutrol, a high-osmolar (1 mmol/ml) gadolinium chelate, was employed as contrast agent because of chronic renal failure and substantial risk for iodinated contrast-associated nephrotoxicity. In both patients gadobutrol yielded high-quality images without digital subtraction and was well tolerated with no ensuing renal dysfunction.

Reversible microvascular dysfunction coupled with persistent myocardial dysfunction: implications for post-infarct left ventricular remodelling.

BACKGROUND: Recent studies have shown that microvascular dysfunction after myocardial infarction is a dynamic phenomenon. AIMS: To evaluate the implications of dynamic changes in microvascular dysfunction on contractile recovery and left ventricular remodelling, and to identify the ideal timing of assessment of such microvascular dysfunction. METHODS AND RESULTS: In 39 patients with a first myocardial infarction who underwent successful percutaneous coronary intervention, microvascular dysfunction was studied by myocardial contrast echocardiography (MCE) at 24 h, 1 week and 3 months after the procedure. Real-time MCE was performed by contrast pulse sequencing and intravenous Sonovue. 14 patients exhibited left ventricular remodelling at 3 months (>20% increase in left ventricular end-diastolic volume, group B), whereas 25 did not (group A). Microvascular dysfunction was similar in the two groups at 24 h and improved in group A only, being significantly better than that of group B at 1 week (p<0.05) and 3 months (p<0.005). Improvement in microvascular dysfunction was not associated with improvement in wall motion in the same segments. With multivariate analysis including all echocardiographic variables, microvascular dysfunction at 1 week was found to be the only independent predictor of left ventricular remodelling (p<0.01). With a cut-off value of 1.4, 1-week microvascular dysfunction predicts left ventricular remodelling with sensitivity and specificity of 73%. CONCLUSIONS: Improvement in microvascular dysfunction occurs early after myocardial infarction, although it is not associated with a parallel improvement in wall motion but is beneficial in preventing left ventricular remodelling. Accordingly, 1-week microvascular dysfunction is a powerful and independent predictor of left ventricular remodelling.