The usefulness of QRS Index for prediction of echocardiographic response in cardiac resynchronization therapy: a multicenter study.

BACKGROUND: The association between QRS narrowing and response to cardiac resynchronization therapy (CRT) has been investigated by several studies, but their findings remain inconclusive. Aim of our study was to explore the relationship between QRS Index and echocardiographic response to CRT. METHODS: This multicenter, retrospective analysis included 326 consecutive patients (mean age was 70.0±10.1 years old; males 76.7%) who underwent CRT-D implantation in primary and secondary prevention between 2018 and 2020. The estimation of QRS shortening after CRT-D implantation was precisely assessed through the QRS Index, calculated as follows: [(QRS duration before implantation - paced QRS duration)/QRS duration before implantation]*100. RESULTS: After a mean follow-up of 12.7±4.5 months, 55.2% (180/326) of the patients showed an echocardiographic response to CRT. The median [25-75th] QRS Index was 3.85% [-14.1% - +13.9%]. The best predictive cut-off value of QRS Index was 1.40% (sensitivity 70.4%, specificity 64.5%, AUC 0.70). In patients with left bundle branch block, the median [25-75th] QRS Index was 9.85% [+3.87% - +16.7%]. In this subgroup, the AUC was 0.737 and the best predictive cut-off of QRS Index was 2.20% (sensitivity 78.3%, specificity 67%). The multivariable model showed that only left ventricular ejection fraction and QRS Index were independently associated with CRT response (respectively OR 0.92, CI 95% 0.86-0.98, P=0.01 and OR 1.057, CI 95% 1.026-1.089, P<0.001). CONCLUSIONS: The QRS Index tightly correlated with CRT response. Only LVEF and QRS Index were independently associated with echocardiographic response to CRT.

Modeling incomplete penetrance in arrhythmogenic cardiomyopathy by human induced pluripotent stem cell derived cardiomyocytes.

Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are commonly used to model arrhythmogenic cardiomyopathy (ACM), a heritable cardiac disease characterized by severe ventricular arrhythmias, fibrofatty myocardial replacement and progressive ventricular dysfunction. Although ACM is inherited as an autosomal dominant disease, incomplete penetrance and variable expressivity are extremely common, resulting in different clinical manifestations. Here, we propose hiPSC-CMs as a powerful in vitro model to study incomplete penetrance in ACM. Six hiPSC lines were generated from blood samples of three ACM patients carrying a heterozygous deletion of exon 4 in the PKP2 gene, two asymptomatic (ASY) carriers of the same mutation and one healthy control (CTR), all belonging to the same family. Whole exome sequencing was performed in all family members and hiPSC-CMs were examined by ddPCR, western blot, Wes™ immunoassay system, patch clamp, immunofluorescence and RNASeq. Our results show molecular and functional differences between ACM and ASY hiPSC-CMs, including a higher amount of mutated PKP2 mRNA, a lower expression of the connexin-43 protein, a lower overall density of sodium current, a higher intracellular lipid accumulation and sarcomere disorganization in ACM compared to ASY hiPSC-CMs. Differentially expressed genes were also found, supporting a predisposition for a fatty phenotype in ACM hiPSC-CMs. These data indicate that hiPSC-CMs are a suitable model to study incomplete penetrance in ACM.

Voltage mapping of Koch's triangle in atrioventricular nodal reentrant tachycardia ablation : Results from an observational multicenter prospective registry.

BACKGROUND: The identification of a "low-voltage bridge" to guide ablation of atrioventricular nodal reentry tachycardia (AVNRT) has been described as a safe and effective strategy in children. We investigated the presence of a low-voltage bridge in adult patients undergoing AVNRT ablation, to evaluate its anatomical correspondence with the successful ablation site. We also investigated the possible correlations between Koch's triangle anatomy and patients' biometric characteristics. METHODS: This observational registry prospectively collected data from 200 patients undergoing AVNRT ablation, guided by 3D electroanatomical mapping system, in 6 electrophysiology centers. Koch's triangle voltage map was collected; then, the anatomical correspondence between the low-voltage bridge and the successful ablation site was evaluated. Koch's triangle anatomical dimensions were subsequently drawn from the mapping system and correlated to patients' gender, age, and weight. RESULTS: The low-voltage bridge was identified in 159 over 200 procedures (79.5%). When the low-voltage bridge was identified, its anatomical correspondence with the successful ablation site has been proved in 137 over 159 cases (86%), with a reduction of radiofrequency deployment time. No strict correlations were found, on the other side, between Koch's triangle anatomy and patients' biometric data. CONCLUSIONS: The identification of the low-voltage bridge has proved to be a helpful strategy to guide AVNRT ablation in a large cohort of adult patients. Targeting the low-voltage bridge during AVNRT ablation helps to reduce RF application time. Koch's triangle morphological characteristics cannot be predicted on the base of patients' biometric data.

Electrocardiographic predictors of echocardiographic response in cardiac resynchronization therapy: Update of an old story.

BACKGROUND: A better selection of patients with left bundle branch block (LBBB) might increase the response to cardiac resynchronization therapy (CRT). The aim of the study was to investigate the association between the Strauss criteria, absence of S wave in V5-V6, the Selvester score and response to CRT. METHODS AND RESULTS: The retrospective analysis included all consecutive patients having undergone implantation of biventricular defibrillators in primary prevention between 2018 and 2020. The final analysis included 236 patients (mean age 69.7 ± 9.9; 77.5% of males). The Strauss criteria were significantly associated with CRT response (p < 0.01) with a sensitivity of 71.3% and specificity of 64.1%. The Strauss criteria along with the absence of S wave in V5 and V6 showed a sensitivity of 56.7%, a specificity of 82.6% and a positive predictive value of 90.5%. The Selvester score was significantly and inversely associated with CRT response (OR 0.818, 95% CI 0.75-0.89; p < 0.001). The multivariable model showed that left ventricular ejection fraction (LVEF) and QRS duration (≥140 ms in males and ≥ 130 ms in females) were independently associated with CRT response (respectively OR 0.92, CI 95% 0.86-0.98, p = 0.01 and OR 3.70, CI 95% 1.12-12.21, p = 0.03). CONCLUSIONS: Strauss criteria, especially in association with absence of S wave in V5 and V6, were able to increase specificity and positive predictive value for predicting CRT response. The Selvester score was inversely associated with CRT response. Finally, LVEF and QRS duration were independently associated with echocardiographic response to CRT.

Left atrial hypertension invasively measured during pulmonary vein isolation predicts atrial fibrillation recurrence.

BACKGROUND: The clinical role of left atrial hypertension (LAH) in patients with atrial fibrillation (AF) and its role as predictor in those undergoing pulmonary vein (PV) isolation is still unknown. The aim of the present study was to analyse the prevalence of LAH in patients with nonvalvular AF and preserved left ventricular ejection fraction who underwent PV isolation and its implication for AF catheter ablation. METHODS: Consecutive patients with drug resistant AF who underwent PV isolation at San Maurizio Regional Hospital of Bolzano (Italy) as index procedure were retrospectively included in this analysis. Left atrial hypertension was defined as the LA mean pressure ≥15 mmHg. RESULTS: A total of 98 consecutive patients (71 males, 72%; mean age 60.3±8.4 years) were included in the analysis. Eleven patients (11%) underwent radiofrequency ablation and 87 (89%) cryoballoon ablation. The mean LA pressure was 11.7±5.5 mmHg; LAH occurred in 24 (24.5%) patients. At a mean follow-up of 14.6±7.1 months (median 14 months), the success rate without antiarrhythmic therapy was 71.4% (70/98; considering the blanking period). Older age, LA volume and LAH were significantly associated with early AF recurrence during the blanking period. However, only LAH independently remained a significant predictor of late AF recurrence (HR 3.02, 1.36-6.72, P=0.007). CONCLUSIONS: Left atrial hypertension was found in 24% of patients undergoing PV isolation and was found to be significantly related to both early and late AF recurrences.

Oxidized LDL-dependent pathway as new pathogenic trigger in arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is hallmarked by ventricular fibro-adipogenic alterations, contributing to cardiac dysfunctions and arrhythmias. Although genetically determined (e.g., PKP2 mutations), ACM phenotypes are highly variable. More data on phenotype modulators, clinical prognosticators, and etiological therapies are awaited. We hypothesized that oxidized low-density lipoprotein (oxLDL)-dependent activation of PPARγ, a recognized effector of ACM adipogenesis, contributes to disease pathogenesis. ACM patients showing high plasma concentration of oxLDL display severe clinical phenotypes in terms of fat infiltration, ventricular dysfunction, and major arrhythmic event risk. In ACM patient-derived cardiac cells, we demonstrated that oxLDLs are major cofactors of adipogenesis. Mechanistically, the increased lipid accumulation is mediated by oxLDL cell internalization through CD36, ultimately resulting in PPARγ upregulation. By boosting oxLDL in a Pkp2 heterozygous knock-out mice through high-fat diet feeding, we confirmed in vivo the oxidized lipid dependency of cardiac adipogenesis and right ventricle systolic impairment, which are counteracted by atorvastatin treatment. The modulatory role of oxidized lipids on ACM adipogenesis, demonstrated at cellular, mouse, and patient levels, represents a novel risk stratification tool and a target for ACM pharmacological strategies.

Left Atrial Pressure as a Predictor of Success in Catheter Ablation of Atrial Fibrillation in a Real-Life Cohort.

AIMS: The clinical role of the left atrial (LA) hypertension in patients with atrial fibrillation (AF) and its role as predictor in those undergoing pulmonary vein (PV) isolation is still unknown. The aim of the present study was to analyze the role of LA pressure in patients with nonvalvular AF who underwent PV isolation and its implication for AF catheter ablation. METHODS: Consecutive patients with drug resistant AF who underwent PV isolation at San Maurizio Regional Hospital of Bolzano (Italy) as index procedure were included in this analysis. RESULTS: A total of 132 consecutive patients (97 males, 73%; mean age 58.0 ± 13.2 years) were included in the analysis. Eleven patients (8%) underwent radiofrequency ablation and 121 (92%) cryoballoon ablation. Higher LA pressures were found in 54 patients (40.9%). At a mean follow up of 14.3 ± 8.2 months (median 12 months), the success rate without antiarrhythmic therapy was 65.9% (87/132; considering the blanking period). Female gender and continuous mean LA pressure were significantly associated with AF recurrence and remained significant on multivariable Cox analysis (respectively, HR 1.845, 1.00-3.40, p = 0.05 and HR 1.066, 1.002-1.134, p = 0.04). We identified a LA mean pressure of >15 mmHg as ideal cutoff and constructed a model to predict AF recurrence which fitted with a concordance index (C-index) of 0.65 (95% CI 0.56-0.75), logrank score p = 0.003.

Generation and characterization of three human induced pluripotent stem cell lines (EURACi007-A, EURACi008-A, EURACi009-A) from three different individuals of the same family with arrhythmogenic cardiomyopathy (ACM) carrying the plakophillin2 p.N346Lfs*12 mutation.

Arrhythmogenic Cardiomyopathy (ACM) is a genetically based cardiomyopathy associated with ventricular arrhythmias and fibro-fatty substitution of cardiac tissue. It is characterized by incomplete penetrance. We generated human iPSCs by episomal reprogramming of blood cells from three members of the same family: the proband, affected by ACM and carrying the heterozygous plakophillin2 p.N346Lfs*12 mutation, one asymptomatic carrier of the same mutation and one apparently healthy control. hiPSCs were characterized according to standard protocols including karyotyping, pluripotency marker expression and differentiation towards the three germ layers. These hiPSC lines can be used to study the mechanisms of ACM incomplete penetrance in vitro.

Cryoballoon or radiofrequency ablation? Alternating technique for repeat procedures in patients with atrial fibrillation.

BACKGROUND: Which technique is better for repeat ablation in patients with atrial fibrillation (AF) remains unclear. The aim of the study was to compare long-term efficacy of repeat ablation using the alternative technique for the first redo ablation procedure: (a) cryoballoon (CB) re-ablation after a failed index pulmonary vein isolation (PVI) with radiofrequency (RF) ablation, RF-then-CB group or (b) RF repeat ablation following a failed CB ablation, CB-then-RF group. METHODS: Within the 1STOP Italian Project, consecutive patients undergoing repeat ablation with a different technique from the index procedure were included. RESULTS: We studied 474 patients, 349 in RF-then-CB and 125 in CB-then-RF group. Less women (21% vs 30%; P = .041), more persistent AF (33% vs 22%; P = .015), longer duration of AF (60 vs 31 months; P < .001), and more hypertension (50% vs 36%; P = .007) were observed in the RF-then-CB cohort as compared with the CB-then-RF group. The number of reconnected PVs was 3.7 ± 0.7 and 1.4 + 1.3 in RF-then-CB and CB-then-RF group, respectively (P < .001). During the follow-up, significantly less AF recurrence occurred in the CB-then-RF group (22% vs 8%, HR = 0.46; 95% CI: 0.24-0.92; P = .025). Cohort designation was the only independent predictor of AF recurrence. CONCLUSION: Alternation of energy source for repeat ablation was safe and effective, regardless the energy used first. However, patients initially treated with CB PVI undergoing repeat ablation with RF current had less AF recurrence at long-term follow-up as compared with those originally treated by RF ablation receiving a CB repeat ablation.

Lipidomics, Atrial Conduction, and Body Mass Index.

BACKGROUND: Lipids are increasingly involved in cardiovascular risk prediction as potential proarrhythmic influencers. However, knowledge is limited about the specific mechanisms connecting lipid alterations with atrial conduction. METHODS: To shed light on this issue, we conducted a broad assessment of 151 sphingo- and phospholipids, measured using mass spectrometry, for association with atrial conduction, measured by P wave duration (PWD) from standard electrocardiograms, in the MICROS study (Microisolates in South Tyrol) (n=839). Causal pathways involving lipidomics, body mass index (BMI), and PWD were assessed using 2-sample Mendelian randomization analyses based on published genome-wide association studies of lipidomics (n=4034) and BMI (n=734 481), and genetic association analysis of PWD in 5 population-based studies (n=24 236). RESULTS: We identified an association with relative phosphatidylcholine 38:3 (%PC 38:3) concentration, which was replicated in the ORCADES (Orkney Complex Disease Study; n=951), with a pooled association across studies of 2.59 (95% CI, 1.3-3.9; P=1.1×10-4) ms PWD per mol% increase. While being independent of cholesterol, triglycerides, and glucose levels, the %PC 38:3-PWD association was mediated by BMI. Results supported a causal effect of BMI on both PWD ( P=8.3×10-5) and %PC 38:3 ( P=0.014). CONCLUSIONS: Increased %PC 38:3 levels are consistently associated with longer PWD, partly because of the confounding effect of BMI. The causal effect of BMI on PWD reinforces evidence of BMI's involvement into atrial electrical activity.

The assessment of pulmonary vein potentials using the new achieve advance during cryoballoon ablation of atrial fibrillation.

BACKGROUND: The new version of inner lumen mapping catheter (Achieve Advance™; Medtronic, Minnesota, USA) includes a new solid core which provides improved rotational response, as compared to the current Achieve Mapping Catheter. In the present study, we sought to analyze the rate of visualisation of real-time recordings using this new device comparing it with a large cohort of patients having undergone second generation cryoballoon (CB) ablation using the previous Achieve mapping catheter. METHODS: All patients having undergone CB ablation using the Achieve Advance and the last 150 consecutive patients having undergone CB ablation using the previous Achieve were analysed. Exclusion criteria were presence of an intracavitary thrombus, uncontrolled heart failure, moderate or severe valvular disease and contraindications to general anesthesia. RESULTS: A total of 200 consecutive patients (60.1 ±â€¯9.5 years, 75% males) were evaluated (50 Achieve Advance and 150 old Achieve). Real-time recordings were significantly more prevalent in the "new Achieve Advance" population compared with the "old Achieve" group (73.5% vs 56.8%; p = 0.0001). Real-time recordings could be more frequently visualized in the "Achieve Advance" group in all veins except RIPV (LSPV: 86% vs 71.3%, p = 0.04; LIPV: 84% vs 62.7%, p = 0.005; RSPV: 78% vs 52%, p < 0.0001; RIPV: 46% vs 41.3%, p = 0.3). CONCLUSIONS: The rate of visualisation of real-time recordings is significantly higher using the new Achieve Advance if compared to the previous Achieve mapping catheter in the setting of CB ablation. Real-time recordings can be visualized in approximately 73.5% of veins with this new device.

A comparison of 8-mm and open-irrigated gold-tip catheters for typical atrial flutter ablation: Data from a prospective multicenter registry.

BACKGROUND: Cavotricuspid isthmus (CTI) radiofrequency (RF) catheter ablation is the standard treatment for patients suffering from CTI-dependent atrial flutter (AFL). The aim of this study was to compare the use in clinical practice of 8-mm gold-tip catheter (8mmRFC) and open-irrigated gold-tip catheter (irrRFC) for RF typical AFL ablation. METHODS: Patients with typical AFL were treated with 8mmRFC or irrRFC catheters according to investigator preferences. The primary endpoint was the cumulative radiofrequency time (CRFT). Fluoroscopy time, acute and 6-month success rates were secondary endpoints. RESULTS: After excluding 3 patients with left AFL, 157 of the enrolled patients (median age 71.8 [interquartile range, 64.1-76.2], 76% men, 91% in NYHA class ≤II, 65% with no structural heart disease) were analyzed: 74 (47%) subjects were treated with the 8mmRFC and 83 (53%) with the irrRFC. The median CRFT was 3 [2-6] minutes in the 8mmRFC group and 5 [3-7] minutes in the irrRFC group (P = .183). There were no significant differences in ablation success rates, intraprocedural CTI reconnections, audible steam pops, and procedural times. In the 8mmRFC group, a significantly lower fluoroscopy time was observed as compared to the irrRFC group (8 [5-12] vs 15 [10-20] minutes, P < .001). During the follow-up period, AFL recurrences were documented in 3 patients in the 8mmRFC group and 2 in the irrRFC group (P = .655). CONCLUSIONS: The 8mmRFC and the irrRFC performed similarly in routine practice for CTI ablation in terms of cumulative RF time, acute and 6-month success rates. Fluoroscopy time was significantly lower in the 8mmRFC group.

Center experience does not influence long-term outcome and peri-procedural complications after cryoballoon ablation of paroxysmal atrial fibrillation: Data on 860 patients from the real-world multicenter observational project.

BACKGROUND: The aim of this research was to evaluate whether the procedural data, the incidence of complications, and the long-term freedom from atrial fibrillation (AF) recurrences are influenced by center experience in a paroxysmal AF (PAF) population performing a first-time pulmonary vein isolation (PVI) by cryoballoon ablation (CBA). METHODS: A total of 860 patients underwent PVI by CBA. Center experience groups were predefined according to the quartiles of the distribution regarding the amount of performed procedures: 3.1%, 10.6%, 22.7% and 63.6% of patients were respectively followed in each group from 1st (less experienced) to 4th (more experienced) quartile of experience. RESULTS: In the entire population, median procedure and fluoroscopy time were 105 and 25 min, respectively. The median procedure time significantly decreased from 130 to 90 min (P < 0.001) as the center's experience increased. In 47 (5.5%) patients, a peri-procedural complication occurred. As the experience of centers increased, the acute intraprocedural PVI success rate increased (from 94.3% to 98.9%, P = 0.007), whereas there was a tendency towards a decreased incidence of peri-procedure complications (from 7.4% to 4.6%, P = 0.998). The mean 1-year freedom from AF recurrence probability was 78.3%, and the 18-month mean was 68.9% with no difference among the groups with different levels of experience. CONCLUSION: CBA is a safe and effective treatment for patients with PAF. Peri-procedural complications and procedural times were low in all the analyzed sub-groups, showing a decreasing trend in function of center expertise. The long-term freedom from AF recurrence was not influenced by the level of experience. (clinicaltrials.gov: NCT01007474).

Is the time between first diagnosis of paroxysmal atrial fibrillation and cryoballoon ablation a predictor of efficacy?

AIMS: Cryoablation is an indicated therapy for the treatment of recurrent atrial fibrillation through pulmonary vein isolation; however, the optimal time between first diagnosis of atrial fibrillation and cryoablation is still unknown. We aimed to assess the clinical efficacy and safety of early versus later treatment of patients with paroxysmal atrial fibrillation by cryoablation. METHODS: Five hundred and ten patients underwent atrial fibrillation cryoablation and were prospectively followed for at least 6 months in 43 Italian cardiology centers. The population was divided into two groups according to the time since the first diagnosis of atrial fibrillation until the index cryoablation procedure. An early-treatment group had an elapsed time of 15 months or less from atrial fibrillation diagnosis until cryoablation, and the late-treatment group had an elapsed time of greater than 15 months. During the evaluation, clinical efficacy was defined as atrial fibrillation recurrence outside a landmark 90-day blanking period, and safety was defined as the reporting of all procedure-related complications. RESULTS: In the total cohort, cryoablation was performed after a median of 36 months from the point of the patient diagnosis with drug refractory symptomatic recurrent atrial fibrillation. The early-treatment group was composed of 130 (25%) patients, whereas the late-treatment group had 380 (75%) patients. Both cohorts had similar baseline clinical characteristics. Of 510 patients, 22 had a complication related to the procedure with no difference between the two groups. Multivariable analysis showed that the risk of atrial fibrillation recurrence was significantly higher in the late-treatment group (hazard ratio: 1.77; 95% confidence interval 1.00-3.13) CONCLUSION: In our multicenter observational examination, cryoablation was well tolerated and effective in the treatment of patients with drug refractory symptomatic paroxysmal atrial fibrillation. Reducing the time between diagnosis and ablation brought about a treatment that had a lower risk of atrial fibrillation recurrence with no change in safety.(Italian ClinicalService Project: NCT01007474).

Exploring digenic inheritance in arrhythmogenic cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors. METHODS: We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes. RESULTS: We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein's only serine kinase domain. CONCLUSIONS: In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model.

Cardiac resynchronisation therapy associated with pulmonary artery banding in an adult with severe right ventricular dysfunction after Mustard repair for complete transposition of the great arteries: results after 2 years of follow-up.

Late dysfunction of the systemic right ventricle in patients with complete transposition of the great arteries after Mustard or Senning procedures and progressive deterioration of the clinical status has been demonstrated. However, evidence-based data on the effective therapy for systemic right ventricular dysfunction in these patients are yet to be defined. Our patient shows an improvement in the right ventricular systolic function, with a reduction in tricuspid regurgitation and a consequent better exercise tolerance after a hybrid approach consisting of an upgrading of a previous transvenous-implanted dual-chamber Implantable Cardiac Defibrillator to biventricular pacing associated with pulmonary artery banding via an anterior thoracotomy.

Ten years differences in recently onset atrial fibrillation and flutter incidence and management.

ABSTRACT: Ten years differences in recently onset atrial OBJECTS AND BACKGROUND: Atrial fibrillation (AF) and atrial flutter (AFl) are the most common arrhythmias in day-life clinical practice. Purpose of our study was to verify differences occurred in the last ten years in AF and AFI incidence and treatment in the emergency room (ER). METHODS: from the 17th January to the 15th February 2000 and from the 18th January to the 16th February 2010 all the consecutive patients with AF or AFl referring to the ER of our hospital were included in the study. Epidemiological data were collected along with information about treatment, admission to hospital wards, days of hospital stay and therapy. Data from the year 2000 were compared to these collected ten years later. RESULTS: incidence of AF and AFl has increased in the years (50%), patients are older (73.5 vs. 65.2 years; p 0.029) and refer late to the ER (45.6% in 2010 and 23.7% in 2000 with a delay of > 48 hours from arrhythmias onset; p 0.054). In 2010 only a minority of these patients is directly discharged from the ER (15.8% vs 14.4%) and there is an increased admission rate due to AF or AFl (67.5%; p 0.026), if compared to the whole admissions of the hospital. The median duration of hospital stay decreased from 6 days to 4.5 days in the year 2010 (NS). CONCLUSION: AF and AFl incidence is still increasing and account for a high admission rate from the ER to the hospital wards. Costs are consequently continuously increasing.

Influence of time between last myocardial infarction and prophylactic implantable defibrillator implant on device detections and therapies. "Routine Practice" data from the SEARCH MI registry.

BACKGROUND: A multicenter European Registry, SEARCH-MI, was instituted in the year 2002 in order to assess patients' outcomes and ICD interventions in patients with a previous MI and depressed LV function, treated with an ICD according to MADIT II results. In this analysis, we evaluate the influence of the time elapsed between last myocardial infarction (MI) and prophylactic cardioverter defibrillator (ICD) implant on device activations. METHODS: 643 patients with left ventricular dysfunction (mean LVEF 26 ± 5%) and NYHA class I-III were prospectively followed for 1.8 ± 1.2 years in a multicenter registry. The population was divided into 3 groups according to the time between last MI and ICD implant: [1] from 40 days to less than 1.5 years; [2] from 1.5 to less than 7 years and [3] at least 7 years. RESULTS: The cumulative incidence of ventricular tachyarrhymias and appropriate device therapy (ATP or shock) were higher in patients implanted longer time from last MI (Gray's Test p=0.002 and p=0.013 respectively). No significant differences were seen in all cause mortality (Gray's Test p=0.618) or sudden cardiac death across the MI stratification groups (Gray's Test p=0.663). CONCLUSIONS: Patients implanted with an ICD longer after the MI have a higher chance of presenting ventricular tachyarrhythmias and appropriate ICD therapy, while no differences were seen in overall mortality. These observations may be important for improving patient targeting in sudden death prevention.

Physiopathologic correlates of intrathoracic impedance in chronic heart failure patients.

BACKGROUND: Increased plasma levels of amino-terminal fraction of brain natriuretic peptide (NT-proBNP) and alterations of diastolic filling as described by Doppler transmitral flow pattern are well-known markers of decompensated heart failure (HF). Recently, some implantable defibrillators have allowed monitoring of intrathoracic impedance, which is related to lung water content, potentially indicating HF deterioration. The aim of this study was to assess the correlation between intrathoracic impedance and NT-proBNP and echo-Doppler transmitral flow indexes. METHODS: Data were collected from 111 HF patients, in six Italian centers. All patients were on optimal medical therapy. Device diagnostics, echographic data, NT-proBNP determination, and clinical status as assessed by the Heart Failure Score (HFS) were registered at baseline, at bimonthly visits, and at unscheduled examinations due to HF decompensation or device alerts. RESULTS: Over a median follow-up of 413 days, 955 examinations were performed. Intrathoracic impedance was significantly correlated with NT-proBNP (P = 0.013) and with mitral E-wave deceleration time (DtE) (P = 0.017), but not with HFS. At the time of confirmed alert events, NT-proBNP was significantly higher than during confirmed nonalert event examinations; DtE did not differ, whereas impedance was significantly lower. CONCLUSION: A decrease in intrathoracic impedance is inversely correlated with NT-proBNP and directly correlated with DtE. Intrathoracic impedance monitoring therefore has the physiologic basis for being a useful tool to identify early HF decompensation.

Clinical and arrhythmic outcomes after implantation of a defibrillator for primary prevention of sudden death in patients with post-myocardial infarction cardiomyopathy: The Survey to Evaluate Arrhythmia Rate in High-risk MI patients (SEARCH-MI).

AIMS: To evaluate clinical and arrhythmic outcomes in post-infarction cardiomyopathy patients implanted with a defibrillator (ICD) for primary prevention of sudden death. METHODS AND RESULTS: The SEARCH-MI registry is a European multi-centre, prospective, observational study enrolling patients after myocardial infarction, chronic left ventricular dysfunction and an ICD implanted for primary prevention of sudden death. Data on 556 patients with at least one recorded follow-up are presented. Survey to Evaluate Arrhythmia Rate in High-risk MI (SEARCH-MI) patients were sicker than those enrolled in MADIT-II with higher New York Heart Association class and left bundle branch block. Total mortality was 10.4%. Close to one-third (30%) of patients experienced episodes of sustained ventricular arrhythmia. One-quarter (23%) received at least one appropriate therapy and 10% inappropriate therapy. Gender (25% males vs. 5% females, P = 0.0009) and history of non-sustained ventricular tachycardia (24% with vs. 18% without P = 0.037) were predictive of appropriate ventricular therapy. CONCLUSION: SEARCH-MI represents the current clinical management of post-MI patients with left ventricular dysfunction indicated to defibrillator implant for primary prevention. European routine clinical practice was influenced by landmark trials and guidelines which impacted on the implantation of cardiac resynchronization therapy in over 25% of such patients. Non-sustained ventricular tachycardia identifies subjects with a higher incidence of appropriate ICD therapy.