Search

Objectives We assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Background Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. Methods Patients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MOI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), PM10, and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. Results We included 126 patients (median age: 67.0 years of age; interquartile range: 55.5-76.0; 97 male patients [77.0%]). Sixty-six patients (52.4%) had PR as the mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels than to IFC, and PM2.5 was independently associated with PR (odds ratio: 1.194; 95% CI: 1.036 to 1.377; P = 0.015). Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MOI at the culprit site. Interestingly, PM2.5, PM10, and C o levels were positively and significantly correlated with serum levels of C-reactive protein. Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is associated with the presence of vulnerable plaque features and with plaque rupture as a mechanism of coronary instability. An enhanced systemic and plaque inflammatory activation may explain these findings.

Background Takotsubo syndrome (TTS) is an acute and reversible form of myocardial injury often preceded by an emotional or physical stressful event. Of importance, TTS may be associated to serious adverse in-hospital complications. Coronary angiography and left ventricle angiography remain a cornerstone for TTS diagnosis. However, the prognostic role of invasively assessed left ventricular end-diastolic pressure (LVEDP) at the time of cardiac catheterization has never been investigated. Purpose We evaluated the role of invasively assessed LVEDP for predicting in-hospital complications in TTS patients compared to the most widely used echocardiographic parameters of ventricular function. Methods We prospectively enrolled 130 patients (mean age 71.2±11.3 years, 114 [87.7%] female) with TTS. Invasive measurement of LVEDP was performed at the time of cardiac catheterization. The rate of in-hospital complications (composite of acute heart failure, cardiogenic shock, life-threatening arrhythmias and all-cause death) was examined. Results In-hospital complications occurred in 37 (28.5%) patients. Patients who experienced in-hospital complications had a higher prevalence of neurological trigger and lower prevalence of emotional trigger, higher LVEDP and mean E/e' ratio and lower LV ejection fraction (LVEF) values compared to those who did not experience in-hospital complications. At multivariable Cox regression, higher LVEDP (hazard ratio [HR] 1.12, 95% confidence interval [CI] [1.05–1.20], p Conclusions LVEDP measured at the time of cardiac catheterization may help in identifying TTS patients at higher risk of cardiovascular events during the hospitalization with relevant therapeutic implications. Of note, in the prediction of in-hospital events the LEVDP performed better than non-invasive indexes commonly used for the assessment of diastolic function. Funding Acknowledgement Type of funding sources: None.

AIMS Killip classification is a simple and fast clinical tool for risk stratification of patients presenting with acute coronary syndrome (ACS). However, the clinical features and predictors of high Killip class at admission, and its prognostic impact in patients presenting with anterior ST elevation MI (STEMI) as first clinical cardiovascular event are still poorly known. The aim of this study was to identify the predictors of high Killip class and its impact on in-hospital and follow-up outcomes. METHODS We prospectively enrolled patients with unheralded anterior STEMI because of proximal or mid left anterior descending (LAD) artery categorized according to Killip classification. Patients' characteristics, in-hospital complications and major adverse cardiovascular events (MACEs; composite of all-cause death, heart failure hospitalization and new-onset ACS) at follow-up were collected. RESULTS We enrolled 147 patients [age 66.16±13.33, 113 male patients (76.9%)]. Killip class III--IV occurred in 22 (15%) patients. The median duration of follow-up was 12 [6--15.1] months. At multivariate analysis age [hazard ratio 1.137, 95% CI (1.068--1.209), P < 0.001], prehospital cardiac arrest [hazard ratio 12.145, 95% CI (1.710--86.254), P = 0.013] and proximal LAD lesion [hazard ratio 5.066, 95% CI (1.400--18.334), P = 0.013] were predictive of Killip class III--IV at admission. At multivariate analysis, Killip class III--IV was an independent predictor of in-hospital mortality [hazard ratio 7.790, 95% CI (1.024--59.276], P = 0.047 and of MACEs [hazard ratio 4.155 (1.558--11.082), P = 0.004) at follow-up. CONCLUSION Killip classification performed at the time of admission is a simple and useful clinical marker of a high risk of early and late adverse cardiovascular events.

AimsTakotsubo syndrome (TTS) is associated to serious adverse in-hospital complications. We evaluated the role of invasively assessed left ventricular end-diastolic pressure (LVEDP) for predicting in-hospital complications in TTS patients compared to the most widely used echocardiographic parameters of ventricular function.Methods and Results We prospectively enrolled 130 patients (mean age 71.2 ± 11.3 years, 114 [87.7%] female) with TTS. Invasive measurement of LVEDP was performed at the time of cardiac catheterization. The rate of in-hospital complications (composite of acute heart failure, life-threatening arrhythmias and all-cause death) was examined. In-hospital complications occurred in 37 (28.5%) patients. Patients who experienced in-hospital complications had a higher prevalence of neurological trigger and lower prevalence of emotional trigger, higher LVEDP and mean E/e′ ratio and lower LV ejection fraction (LVEF) values compared to those who did not experience in-hospital complications. At multivariate logistic regression, higher LVEDP [odds ratio (OR) 1.12, 95% confidence interval (CI) [1.05–1.20], P Conclusions LVEDP measured at the time of catheterization may help in identifying TTS patients at higher risk of cardiovascular deterioration with relevant therapeutic implications.

Funding Acknowledgements Type of funding sources: None. Background High-flow nasal cannulae oxygen therapy (HFNCOT) represents a better tolerated alternative to non-invasive pressure support ventilation (NIPSV) for acute cardiogenic pulmonary edema (ACPE) treatment. However, there are still few data on the effect of HFNCOT on cardiac function and hemodynamic. Purpose To assess and compare the effects of NIPSV and HFNCOT in ACPE setting on right ventricular (RV) systolic function and on indices of cardiac filling and output, as measured by echocardiography. Methods This is a cross-over controlled study, enrolling 15 consecutive patients admitted to our Cardiovascular Intensive Care Unit for ACPE and hypoxaemic, normo/hypocapnic acute respiratory failure, with P/F ratio < 200. Each patient received NIPSV, followed by HFNCOT. Full echocardiographic assessment and blood gas analysis (BGA) were performed 40 minutes from onset of each ventilation modality, respectively before NIPSV to HFNCOT switch and before HFNCOT interruption. In particular, RV function parameters, together with RV and atrial strain, were prospectively collected. Results In spite of not significant changes in BGA, RV function was significantly improved under HFNCOT, as compared to NIPSV, as assessed by the following parameters: tricuspid annular plane excursion (TAPSE) (P = 0.001), RV S’ wave (P = 0.007), RV fractional area change (RVFAC) (P = 0.006). Strain analysis confirmed the significant improvement in RV function, with free wall global longitudinal strain (GLS) and free wall and septum GLS significantly higher under HFNCOT, as compared to NIPSV (-21% vs -18% P Conclusions NIPSV significantly affect RV function making more complex the management of patients presenting with ACPE. In this setting, HFNCOT represents a valuable alternative, providing similar respiratory outcomes while preserving good right ventricle performance.

ObjectivePatients with Takotsubo syndrome (TTS) present an acute microvascular dysfunction that leads to an impaired myocardial perfusion and, in more severe forms, an impaired epicardial flow. However, clinical relevance of a delayed coronary flow, the coronary slow flow (CSF), has never been investigated. We studied the prognostic value of CSF occurring in the acute phase of TTS.MethodsThis cohort study prospectively evaluated patients with a diagnosis of TTS. CSF was defined as angiographically non-obstructive coronary arteries with thrombolysis in myocardial infarction-2 flow. The incidence of overall mortality and major adverse cardiovascular events (MACEs), defined as the composite of TTS recurrence, cardiac rehospitalisation, cerebrovascular events and mortality, was assessed at follow-up.ResultsWe enrolled 101 patients (mean age 71.0±11.1 years, 86 (85.1%) female); CSF occurred in 18 (17.8%) patients. At admission, patients with CSF presented more frequently with Killip class III/IV, moderate-to-severe left ventricle systolic dysfunction and right ventricle dysfunction. During the index admission, patients with CSF had a higher rate of intrahospital complications (12 (66.7%) vs 28 (33.7%), p=0.01). At long-term follow-up, patients with CSF had a significantly higher occurrence of overall mortality (9 (50%) vs 19 (22.9%), p=0.011), mainly due to non-cardiac causes (89.3%), and a higher rate of MACE (10 (55.5%) vs 27 (32.5%), p=0.06). At multivariable Cox regression, CSF was independently associated with death from any causes.ConclusionsPatients with TTS presenting with CSF have a worse clinical presentation with a higher rate of intrahospital complications and a poor long-term clinical outcome.

Background Few studies prospectively assessed risk factors for ventricular fibrillation (VF) during a first myocardial infarction (MI). We designed a nation-wide study aiming to identify clinical and genetic characteristics associated with primary VF; and report here about clinical features. Methods PREDESTINATION (PRimary vEntricular fibrillation and suDden dEath during a firST myocardIal iNfArcTION) is an Italian case-control, prospective multicentre study. Cases are patients aged 18–80years with a first MI and at least one VF episodes occurring within 24h of symptoms onset, before reperfusion. Cases and controls are paired 1: 2 by gender and age (±5years). Results Among 1026 patients enrolled between 2007 and 2017, 970 entered the primary analysis: 375 cases and 595 controls (mean age 59years, 85% males). Multivariable analysis identified 5 independent predictors of primary VF: systolic blood pressure (OR 0.982, 95% CI: 0.98–0.99 for each mmHg) and K+ levels + levels obtained after VF, the OR associated with K+ levels Conclusions The present study identified 5 independent predictors of primary VF: familiarity, anterior MI, low systolic blood pressure, physical inactivity and hypokalaemia. Importantly, the last two risk factors are modifiable and, especially in the presence of a family history of sudden death, they should be avoided as much as possible.

There is a growing interest in the study of the mechanisms of heart and brain interactions with the aim to improve the management of high-impact cardiac rhythm disorders, first of all atrial fibrillation. However, there are several topics to which the scientific interests of cardiologists and neurologists converge constituting the basis for enhancing the development of neuro-arrhythmology. This multidisciplinary field should cover a wide spectrum of diseases, even beyond the classical framework corresponding to stroke and atrial fibrillation and include the complex issues of seizures as well as loss of consciousness and syncope. The implications of a more focused interaction between neurologists and cardiologists in the field of neuro-arrhythmology should include in perspective the institution of research networks specifically devoted to investigate 'from bench to bedside' the complex pathophysiological links of the abovementioned diseases, with involvement of scientists in the field of biochemistry, genetics, molecular medicine, physiology, pathology and bioengineering. An investment in the field could have important implications in the perspectives of a more personalized approach to patients and diseases, in the context of 'precision'medicine. Large datasets and electronic medical records, with the approach typical of 'big data' could enhance the possibility of new findings with potentially important clinical implications. Finally, the interaction between neurologists and cardiologists involved in arrythmia management should have some organizational implications, with new models of healthcare delivery based on multidisciplinary assistance, similarly to that applied in the case of syncope units.

An increasing number of detection tools are available and several detection strategies have been described to pursue the diagnosis of atrial fibrillation to prevent ischemic stroke. Monitoring tools include standard electrocardiography, snapshot single-lead recordings with professional or personal devices (e.g. smartphone-based), Holter monitor, external devices with long-term recording capabilities, and cardiac implantable electronic devices, including pacemakers, implantable cardioverter defibrillators and insertable cardiac monitors. Insertable cardiac monitors have shown high sensitivity and specificity for the detection of atrial fibrillation, allow up to three years of continuous monitoring, do not require cooperation of the patient, are well tolerated, have a short device-related time delay between detection of atrial fibrillation and notification to the physician, provide information on atrial fibrillation burden and are minimally invasive. On the other hand, insertable cardiac monitors require a considerable use of resources to process the recordings and have a significant initial cost. Studies conducted with insertable cardiac monitors on patients with prior stroke and on patients with risk factors for stroke but no prior cerebrovascular events or atrial fibrillation have consistently shown a measurable incidence of atrial fibrillation at follow-up. However, the effectiveness of oral anticoagulations in reducing the incidence of ischemic stroke in patients with atrial fibrillation lasting less than 24 h, though reasonable, is currently unproven. The future of atrial fibrillation detection tools and atrial fibrillation detection strategies will be influenced by ongoing studies exploring whether oral anticoagulations reduce the incidence of stroke in patients with atrial fibrillation burden lower than 24 h.

Radiofrequency catheter ablation (RFCA) of supraventricular tachyarrhythmias carries a small but non-negligible radiation risk. Studies in children already showed the feasibility of using three-dimensional mapping systems as the primary guide for catheter visualization and positioning in these RFCAs. We aim to demonstrate the feasibility and safety of such an approach in young and middle-aged patients.Fifty patients (age 34 ± 12) with supraventricular tachyarrhythmias underwent electrophysiological study; of these, 47 patients proceeded to RFCA guided by the EnSite NavX(TM) system (23 with atrioventricular nodal reentry tachycardia, 16 with an accessory pathway, six with typical atrial flutter, and two with right atrial tachycardia).In 38/50 cases (76%), electroanatomical mapping avoided fluoroscopy entirely, including four cases requiring access to the left heart chambers by a retrograde approach. In the remaining 12/50 cases (24%), fluoroscopy use was limited to 122 ± 80 s, with a correspondingly low radiation exposure (dose area product 1.3 ± 1.1 mGy × m(2)). All procedures were acutely successful, with a procedural time of 113 ± 37 minutes, and without incurring in any major complication. Over a mean follow-up of 12 ± 3 months, we observed one recurrence of pre-excitation and one relapse of atrial flutter.Our study shows that non-fluoroscopic RFCA of supraventricular tachyarrhythmias using the EnSite NavX(TM) system is feasible, safe, and effective in a population of relatively young adults. Our experience of a non-fluoroscopic approach in these procedures deserves consideration, particularly in the young or in other patients at higher radiation risk.

The Andersen-Tawil syndrome (ATS) is characterized by hypo-normokaliemic muscle periodic paralysis, dysmorphic features and ventricular arrhythmias. Most cases are caused by mutations in KCNJ2, encoding for the potassium inwardly rectifying channel, Kir2.1 (ATS1). Although KCNJ2 mutations show no obvious genotype-phenotype correlations and incomplete penetrance, signs of cardiac involvement are usually present in most ATS1 cases. In contrast, here we describe an Italian ATS1 patient, carrying a c.574A→G mutation in KCNJ2, who had both facial dysmorphisms and muscle periodic paralysis but who did not manifest any cardiac involvement, although the same mutation was originally described in a Japanese kindred, in which all affected individuals manifested a severe cardiac phenotype.

We assessed predictors of atrial fibrillation (AF) in cryptogenic stroke (CS) or transient ischemic attack (TIA) patients who received an insertable cardiac monitor (ICM).We studied patients with CS/TIA who were randomized to ICM within the CRYSTAL AF study. We assessed whether age, sex, race, body mass index, type and severity of index ischemic event, CHADS2 score, PR interval, and presence of diabetes, hypertension, congestive heart failure, or patent foramen ovale and premature atrial contractions predicted AF development within the initial 12 and 36 months of follow-up using Cox proportional hazards models.Among 221 patients randomized to ICM (age 61.6 ± 11.4 years, 64% male), AF episodes were detected in 29 patients within 12 months and 42 patients at 36 months. Significant univariate predictors of AF at 12 months included age (hazard ratio [HR] per decade 2.0 [95% confidence interval 1.4-2.8], p = 0.002), CHADS2 score (HR 1.9 per one point [1.3-2.8], p = 0.008), PR interval (HR 1.3 per 10 milliseconds [1.2-1.4], p0.0001), premature atrial contractions (HR 3.9 for123 vs 0 [1.3-12.0], p = 0.009 across quartiles), and diabetes (HR 2.3 [1.0-5.2], p0.05). In multivariate analysis, age (HR per decade 1.9 [1.3-2.8], p = 0.0009) and PR interval (HR 1.3 [1.2-1.4], p0.0001) remained significant and together yielded an area under the receiver operating characteristic curve of 0.78 (0.70-0.85). The same predictors were found at 36 months.Increasing age and a prolonged PR interval at enrollment were independently associated with an increased AF incidence in CS patients. However, they offered only moderate predictive ability in determining which CS patients had AF detected by the ICM.

Background: Insertable cardiac monitors (ICM) have been shown to detect atrial fibrillation (AF) at a higher rate than routine monitoring methods in patients with cryptogenic stroke (CS). However, it is unknown whether there are topographic patterns of brain infarction in patients with CS that are particularly associated with underlying AF. If such patterns exist, these could be used to help decide whether or not CS patients would benefit from long-term monitoring with an ICM. Methods: In this retrospective analysis, a neuro-radiologist blinded to clinical details reviewed brain images from 212 patients with CS who were enrolled in the ICM arm of the CRYptogenic STroke And underLying AF (CRYSTAL AF) trial. Kaplan-Meier estimates were used to describe rates of AF detection at 12 months in patients with and without pre-specified imaging characteristics. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were calculated using Cox regression. Results: We did not find any pattern of acute brain infarction that was significantly associated with AF detection after CS. However, the presence of chronic brain infarctions (15.8 vs. 7.0%, HR 2.84, 95% CI 1.13-7.15, p = 0.02) or leukoaraiosis (18.2 vs. 7.9%, HR 2.94, 95% CI 1.28-6.71, p < 0.01) was associated with AF detection. There was a borderline significant association of AF detection with the presence of chronic territorial (defined as within the territory of a first or second degree branch of the circle of Willis) infarcts (20.9 vs. 10.0%, HR 2.37, 95% CI 0.98-5.72, p = 0.05). Conclusions: We found no evidence for an association between brain infarction pattern and AF detection using an ICM in patients with CS, although patients with coexisting chronic, as well as acute, brain infarcts had a higher rate of AF detection. Acute brain infarction topography does not reliably predict or exclude detection of underlying AF in patients with CS and should not be used to select patients for ICM after cryptogenic stroke.

The objective of the study was to better characterize the clinical phenotype associated with the A8344G "MERRF" mutation of mitochondrial DNA. Fifteen mutated patients were extensively investigated. The frequency of main clinical features was: exercise intolerance and/or muscle weakness 67 %, respiratory involvement 67 %, lactic acidosis 67 %, cardiac abnormalities 53 %, peripheral neuropathy 47 %, myoclonus 40 %, epilepsy 40 %, ataxia 13 %. A restrictive respiratory insufficiency requiring ventilatory support was observed in about half of our patients. One patient developed a severe and rapidly progressive cardiomyopathy requiring cardioverter-defibrillator implantation. Five patients died of overwhelming, intractable lactic acidosis. Serial muscle MRIs identified a consistent pattern of muscle involvement and progression. Cardiac MRI showed non-ischemic late gadolinium enhancement in the left ventricle inferolateral part as early sign of myocardial involvement. Brain spectroscopy demonstrated increased peak of choline and reduction of N-acetylaspartate. Lactate was never detected in brain areas, while it could be documented in ventricles. We confirm that muscle involvement is the most frequent clinical feature associated with A8443G mutation. In contrast with previous reports, however, about half of our patients did not develop signs of CNS involvement even in later stages of the disease. The difference may be related to the infrequent investigation of A8344G mutation in 'pure' mitochondrial myo-cardiomyopathy, representing a bias and a possible cause of syndrome's underestimation. Our study highlights the importance of lactic acidosis and respiratory muscle insufficiency as critical prognostic factors. Muscle and cardiac MRI and brain spectroscopy may be useful tools in diagnosis and follow-up of MERRF.

Background —Enhanced coronary vasomotion may contribute to acute coronary occlusion during the acute phase of myocardial infarction (AMI). Japanese have a higher incidence of variant angina than Caucasian patients, but racial differences in vasomotor reactivity early after AMI are controversial. Methods and Results —The same team studied 15 Japanese and 19 Caucasian patients within 14 days of AMI by acetylcholine injection into non–infarct-related (NIRA) and infarct-related (IRA) coronary arteries followed by nitroglycerin. Incidence of vasodilation, vasoconstriction, spasm, and basal tone were assessed in proximal, middle, and distal segments after each drug bolus by quantitative angiography. Japanese patients had much lower cholesterol levels than Caucasians (183±59 versus 247±53 mg/dL, P P P P Conclusions —Soon after AMI, Japanese patients exhibited a 3-fold-greater incidence of spasm and greater vasoconstriction of nonspastic segments after acetylcholine than Caucasians. The causes of such differences warrant further investigation because they may have relevant pathophysiological and therapeutic implications.

Background Patients with atrial fibrillation (AF) are at increased risk for ischemic stroke. In patients who have suffered a stroke, screening for AF is routinely performed only for a short period after the stroke as part of the evaluation for possible causes. If AF is detected after an ischemic stroke, oral anticoagulation therapy is recommended for secondary stroke prevention. In 25% to 30% of stroke patients, the stroke mechanism cannot be determined (cryptogenic stroke). The incidence of paroxysmal AF undetected by short-term monitoring in patients with cryptogenic stroke is unknown, but has important therapeutic implications on patient care. The optimum monitoring duration and method of AF detection after stroke are unknown. The purpose of this study is to evaluate the incidence of AF and time to AF detection in patients with cryptogenic stroke using an insertable cardiac monitor. Study Design The CRYSTAL AF trial is a randomized prospective study to evaluate a novel approach to long-term monitoring for AF detection in patients with cryptogenic stroke. Four hundred fifty cryptogenic stroke patients (by definition, without a history of AF) will be enrolled at approximately 50 sites in Europe, Canada, and the United States. Patients will be randomized in a 1:1 fashion to standard arrhythmia monitoring (control arm) or implantation of the subcutaneous cardiac monitor (Reveal XT; Medtronic, Inc, Minneapolis, MN) (continuous monitoring arm). Outcomes The primary end point is time to detection of AF within 6 months after stroke. The clinical follow-up period will be at least 12 months. Study completion is expected at the end of 2012.

Objective Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adults. DM1 is a multisystem disorder also affecting the heart with an increased incidence of sudden death, which has been explained with the common impairment of the conduction system often requiring pacemaker implantation; however, the occurrence of sudden death despite pacemaker implantation and the observation of major ventricular arrhythmias generated the hypothesis that ventricular arrhythmias may play a causal role as well. The aim of the study was to assess the 2-year cumulative incidence and the value of noninvasive and invasive findings as predictive factors for sudden death, resuscitated cardiac arrest, ventricular fibrillation, sustained ventricular tachycardia and severe sinus dysfunction or high-degree atrioventricular block. Methods/design More than 500 DM1 patients will be evaluated at baseline with a clinical interview, 12-lead ECG, 24-h ECG and echocardiogram. Conventional and nonconventional indications to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implantation have been developed. In the case of an indication to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implant at baseline or at follow-up, the patient will be referred for the procedure. At the end of 2-year follow-up, all candidate prognostic factors will be tested for their association with the endpoints. Trial registration ClinicalTrials.gov ID NCT00127582. Conclusion The available evidence supports the hypothesis that both bradyarrhythmias and tachyarrhythmias may cause sudden death in DM1, but the course of cardiac disease in DM1 is still unclear. We expect that this large, prospective, multicenter study will provide evidence to improve diagnostic and therapeutic strategies in DM1.

In the early phase of T1DM, the prevalence of such abnormalities are unknown. We analysed ECG features in young T1DM patients and in controls. onger mean ura on vs con ro s: 98.7±14.3 vs 90.8±11.1 ms (P

Background Hypertrophic cardiomyopathy (HCM) is associated with increased plasma brain natriuretic peptide (BNP), but sequential plasma and myocardial BNP assessment in stable and dilated HCM has never been performed. Methods and Results Forty consecutive HCM patients (42 ± 8 years, 25 males) underwent cardiac catheterization, angiography, and left ventricular (LV) endomyocardial biopsy. During follow-up (70.5 ± 6.7 months), 30 patients (Group 1) remained stable whereas 10 patients (Group 2) progressed to dilated phase. Group 2 patients underwent a second invasive study with LV biopsy. BNP plasma levels were measured at baseline and at follow-up in all patients. All biopsies were processed for histology and immunohistochemistry with anti-BNP antibodies. BNP plasma levels remained unchanged in Group 1, whereas it significantly increased in all Group 2 patients who exhibited an elevation of LV and right ventricular end-diastolic pressure. Immunohistochemistry showed an increase of BNP-positive myocytes in follow-up biopsies when compared with baseline (75.0 ± 15.0 % versus 29.8 ± 10.0 %; P = .005) with a significant correlation with LV end-diastolic pressure (r = 0.78, P < .001) and plasma BNP (r = 0.83, P < .001). Conclusions Progression to end-stage of HCM is characterized by further increase of myocardial and plasma BNP. Serial assessment of plasma BNP may provide noninvasive recognition of hemodynamic deterioration, allowing prompt institution of heart failure therapy.

Heart Rate Turbulence in Myotonic Dystrophy. Introduction: Myotonic dystrophy type 1 (MD1) is the most common muscular dystrophy of adult life. Cardiac involvement is characterized by disorders of atrioventricular conduction, ventricular arrhythmias, and sudden death. Heart rate turbulence (HRT) is a noninvasive risk predictor in patients affected by ischemic heart disease. The aim of our study is to assess the prognostic value of HRT in MD1 patients. Methods and Results: We performed HRT analysis by 24-hour Holter recording to calculate turbulence onset (TO) and turbulence slope (TS) in 29 MDl patients (mean age 52 ± 10 years), and in 30 patients (mean age 52 ± 13 years) with frequent ventricular arrhythmias and structurally normal heart (VANH). An electrophysiological study (EPS) tested ventricular arrhythmias inducibility in 22 MD1 patients. TO was significantly different between MD1 and VANH patients (-1.66 ± 2.04 and -2.98 ± 1.79%, respectively, P 0.01), while no difference was observed in TS between MDl and VANH patients (11.12 ± 6.46 and 9.12 ± 6 msec/beat, respectively). On EPS, sustained ventricular arrhythmias (SVA) were induced in six MD1 patients. TO was significantly different in inducible MDl patients (0.88 ± 1.95%), as compared with both noninducible (-2.49 ± 1.43%, P < 0.001) or no eligible to EPS (-1.93 ± 1.63%, P < 0.005) MD1 patients and to VANH patients (-2.98 ± 1.79%, P < 0.001). Conclusions: An impairment of TO, a measure of HRT, suggesting impaired cardiac parasympathetic activity, may be a useful, noninvasive predictor of arrhythmic risk in MDl patients.

Patients with ischaemic heart disease and low ejection fraction (EF) are at increased risk of sudden death. MADIT (Multicenter Automated Defibrillator Implantation Trial) II has shown that implantable cardioverter-defibrillators (ICDs) reduce the risk of death by 31% at two years in patients with previous myocardial infarction and EF < 30%.1 The absolute risk reduction over an average follow up of 20 months, however, was only 5.6%. In addition, the high prevalence of patients who have had a myocardial infarction with EF ⩽ 30% makes the cost of this strategy high. This has led to an ongoing search for reliable markers of future episodes of life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) to identify a higher-risk subgroup in which ICD therapy can be more beneficial and cost effective. The difficulty in predicting major ventricular arrhythmias probably reflects a limited understanding of their complex mechanisms. This is particularly true for patients who have had a myocardial infarction and with LV dysfunction, in whom myocardial ischaemia may trigger major ventricular arrhythmias. C reactive protein (CRP) concentration has been shown to be raised both in subjects studied …

Myotonic Dystrophy Type 1. Introduction: Conduction disturbances and arrhythmias characterize the cardiac feature of myotonic dystrophy type 1 (MD1); a myocardial involvement has been suggested as part of the cardiac disease. The aim of our study was to investigate the underlying myocardial alterations using electroanatomic mapping (CARTO) and their possible correlation with genetic and neurological findings. Methods and Results: Right atrial and ventricular CARTO maps were obtained in 13 MD1 patients. Thirteen age-matched patients with paroxysmal supraventricular tachycardia and normal heart served as controls. Unipolar voltage (UNI-v), bipolar voltage (BI-v) amplitudes, bipolar potential duration (Bi-dur), and atrial propagation time (A-pt) were measured. UNI-v and BI-v in interatrial septum, anterolateral atrial wall, and right ventricle outflow tract were lower in MD1 patients than controls (P < 0.001). Bi-dur and A-pt were longer in MD1 patients than controls (P < 0.001, P = 0.046, respectively). A significant relationship was documented between CTG triplets and the percentage of Bi-v

Background— The role of structural heart disease and sodium channel dysfunction in the induction of electrical instability in Brugada syndrome is still debated. Methods and Results— We studied 18 consecutive patients (15 males, 3 females; mean age 42.0±12.4 years) with clinical phenotype of Brugada syndrome and normal cardiac structure and function on noninvasive examinations. Clinical presentation was ventricular fibrillation in 7 patients, sustained polymorphic ventricular tachycardia in 7, and syncope in 4. All patients underwent cardiac catheterization, coronary and ventricular angiography, biventricular endomyocardial biopsy, and DNA screening of the SCN5A gene. Biopsy samples were processed for histology, electron microscopy, and molecular screening for viral genomes. Microaneurysms were detected in the right ventricle in 7 patients and also in the left ventricle in 4 of them. Histology showed a prevalent or localized right ventricular myocarditis in 14 patients, with detectable viral genomes in 4; right ventricular cardiomyopathy in 1 patient; and cardiomyopathic changes in 3. Genetic studies identified 4 carriers of SCN5A gene mutations that cause in vitro abnormal function of mutant proteins. In these patients, myocyte cytoplasm degeneration was present at histology, whereas terminal dUTP nick end-labeling assay showed a significant increase of apoptotic myocytes in right and left ventricle versus normal controls ( P =0.014 and P =0.013, respectively). Conclusions— Despite an apparently normal heart at noninvasive evaluation, endomyocardial biopsy detected structural alterations in all 18 patients with Brugada syndrome. Mutations in the SCN5A gene, identified in 4 of the 18 patients, may have induced concealed structural abnormalities of myocardiocytes that accounted for paroxysmal arrhythmic manifestations.

Aims Retrospective studies have identified a mutation in the lamin A/C (LMNA) gene in patients selected on the basis of a phenotype characterized by dilated cardiomyopathy, atrioventricular conduction disturbances and sudden death. However, the features of cardiac abnormalities in patients with an initial diagnosis of Emery–Dreifuss muscular dystrophy (EDMD) are poorly known. Aim of the present study was to investigate the spectrum of cardiac disease in patients with an initial diagnosis of EDMD caused by a mutation in the LMNA gene. Methods and results Ten consecutive patients with EDMD and a LMNA gene mutation were evaluated with structured medical interview, physical examination, ECG, echocardiogram and 24-h Holter monitoring. Electrophysiological testing and cardiac catheterization were performed if a class 1 or 2 American Heart Association guidelines indication was present. Cardiac disease was found in eight of 10 patients and consisted in the variable combination of supraventricular arrhythmias, disorders of atrioventricular conduction, ventricular arrhythmias, dilated cardiomyopathy, non-dilated cardiomyopathy, restrictive cardiomyopathy and sudden death despite pacemaker implant. Conclusions Cardiac disease is common in patients with an initial diagnosis of EDMD caused by a mutation in the LMNA gene and consists of arrhythmias, disorders of atrioventricular conduction, cardiomyopathies and sudden death despite pacemaker implant.

Biventricular stimulation is a new promising therapy for the treatment of moderate-to-severe heart failure in patients refractory to drug treatment and with contractile dyssynchrony due to conduction delay. The principle on which the resynchronization therapy is based is the reactivation of homogeneous and synchronized contraction by means of atrial-biventricular stimulation. The restoration of greater contraction synchrony seems to produce beneficial effects in the short (e.g., improvement in cardiac output, reduction of mitral regurgitation, increase of dP/dt, reduction of pulmonary wedge pressure) and the medium term (e.g., reduction of left ventricular diameters, increase of ejection fraction, reduction of mitral regurgitation, and reduction of sympathetic activity).

The follow-up of 1440 consecutive post-MI patients (68.9±10.9 years) with an LVEF≤40% was analyzed in 19 Italian hospitals to evaluate how many patients with clinical nonsustained VT and inducible sustained VT or VF underwent post-discharge risk assessment (RA). During 38 (range, 4–76) months follow-up, 611 patients (42.4%) qualified for and 294 (20.4%) effectively underwent RA combining LVEF assessment and Holter monitoring, 29 (2.0%) subsequently underwent programmed electrical stimulation and 19 (1.3%) received an ICD.

The efficacy of implantable cardioverter-defibrillators (ICD) in preventing sudden death has been shown by several trials. Nonetheless two functions need to be improved: (1) the identification of arrhythmias other than VF (supraventricular or ventricular fibrillation) in order to reduce inappropiate shocks, (2) the quality of cardiac pacing. Dual-chamber pacing should be the stimulation method of choice in patients with depressed sinus node function, or in those who are pacemaker dependent, when effective atrial pacing and sensing can be achieved. In contrast, patients with an implatable cardioverter defibrillator (ICD) who also need antibradycardia pacing, can currently receive only fixed rate ventricular pacing, even though most of them have depressed sinus node function. Furthermore, positive hemodynamic effects of atrioventricular sequential pacing in patients with left ventricular dysfunction have been described so far [1, 2]. In fact the preservation of atrioventricular synchronization can result in a positive effect on the morbility and perhaps on the mortality of pacemaker dependent patients [1].

Background: Prolongation of the atrial fibrillation cycle length (AFCL) and termination of AF during ablation have been reported. We investigate the significance of regions of maximal dominant frequency (DF) identified by spectral analysis, determining the effect of ablation at these sites located within the pulmonary veins (PV) on the fibrillatory process. Methods: Thirty-two patients undergoing AF ablation during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126 13 points/pt throughout both atria and coronary sinus (CS). At each point, 5s electrograms were obtained to determine the highest amplitude frequency on spectral analysis and construct 3D DF maps. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at PVs with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient 20%) was evaluated by determining the change in AFCL within the CS before and after isolation of each PV, and the termination of AF. Results: PV ablation was associated with an increase in AFCL (174 27 to 184 35ms; p 0.0001). While ablation at a PV harboring a DF site resulted in AFCL prolongation (180 30 to 198 40ms; p 0.0001), ablation at a PV without a DF site did not change the AFCL (169 22 to 170 22ms; p 0.4). Ablation at PVs harboring a DF site resulted in an increase in AFCL ( 5ms) within the CS in 89% with the mean increase in AFCL of 18 21ms (range 0-118ms) compared to 0.9 3.9ms (range -10 to 7ms; p 0.0001) after ablation at PVs without a DF site. The increase in AFCL with PV ablation demonstrated a strong concordance with ablation at a DF site (kappa-coefficient of 0.77). PV ablation resulted in AF termination in 14 pts; 11 at a DF site. In the remaining 3, 2 had frequent cessation of arrhythmia during mapping. Conclusion: High frequency PV activity identified by spectral analysis has an important role in maintaining AF. Ablation at these sites resulted in slowing of the fibrillatory process and termination of paroxysmal AF.

Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p