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At the beginning of the COVID-19 emergency, non-urgent surgical procedures had to be deferred, but also emergencies were reduced. To assess the global trend of pacemaker (PM) and implantable cardiac-defibrillator (ICD) procedures performed in Italy before, during, and after the first COVID-19 emergency, all the Italian hospital discharge records related to PM/ICD procedures performed between 2012 and 2021, sent to the National Institute of Health, were reviewed. Compared to 2019, in 2020, there was a reduction of first PM implants (52,216 to 43,962, -16%; p < 0.01), but not replacements (16,591 to 17,331, + 4%; p = 0.16). In particular, in April 2020, there was a drop of first implants (- 53,4% vs the average value of April 2018 and April 2019; p < 0.01), while the reduction of replacements was less evident (-32.6%; p = NS). In 2021, PM procedures increased to values similar to the pre-pandemic period. A reduction of ICD procedures was observed in 2020 (22,355, -7% toward 2019), mainly in April 2020 (- 46% vs April 2018/April 2019; p = 0.03). In 2021, the rate of ICD procedures increased (+ 14% toward 2020). A non-significant reduction of "urgent" procedures (complete atrioventricular block for PM and ventricular fibrillation for ICD), even in April 2020, was observed. In 2020, there was a reduction of first PM implants and ICDs, offset by increased activity in 2021. No decrease in PM replacements was observed, and the drop in "urgent" PM and ICD procedures was not statistically significant., (© 2023. The Author(s).)

Background: The subsequent waves of the COVID-19 pandemic in Italy had a major impact on cardiac care., Methods: A survey to evaluate the dynamic changes in arrhythmia care during the first five waves of COVID-19 in Italy (first: March-May 2020; second: October 2020-January 2021; third: February-May 2021; fourth: June-October 2021; fifth: November 2021-February 2022) was launched., Results: A total of 127 physicians from arrhythmia centers (34% of Italian centers) took part in the survey. As compared to 2019, a reduction in 40% of elective pacemaker (PM), defibrillators (ICD), and cardiac resynchronization devices (CRT) implantations, with a 70% reduction for ablations, was reported during the first wave, with a progressive and gradual return to pre-pandemic volumes, generally during the third-fourth waves, slower for ablations. For emergency procedures (PM, ICD, CRT, and ablations), recovery from the initial 10% decline occurred in most cases during the second wave, with some variability. However, acute care for atrial fibrillation, electrical cardioversions, and evaluations for syncope showed a prolonged reduction of activity. The number of patients with devices which started remote monitoring increased by 40% during the first wave, but then the adoption of remote monitoring declined., Conclusions: The dramatic and profound derangement in arrhythmia management that characterized the first wave of the COVID-19 pandemic was followed by a progressive return to the volume of activities of the pre-pandemic periods, even if with different temporal dynamics and some heterogeneity. Remote monitoring was largely implemented during the first wave, but full implementation is needed., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Cardiac surgery in Jehovah's Witnesses (JW) patients who refuse blood transfusion is challenging requiring dedicated strategies. We aimed to analyze non-selected JW patients undergoing cardiac surgery and to compare with matched controls both perioperative outcomes and long-term survival. We retrospectively analyzed JW patients undergoing cardiac surgery from January 2016 to March 2021 and compared them with matched controls. The primary outcome was a composite of in-hospital perioperative adverse events and in-hospital mortality. The secondary outcome was all-cause mortality at long-term follow-up. A total of 113 JW patients and 113 controls were included. Baseline clinical characteristics, including laboratory parameters were comparable. Overall, there were no statistical differences between JW vs controls in terms of in-hospital mortality (2.7% vs 1.8%, p = 1.00) but mortality was remarkably high (40%) in JW patients with post-op hemoglobin < 8 g/dl. Logistic regression analysis found that the JW group was not associated with a higher occurrence of the composite outcome (adjusted odds ratio 0.91, 95% confidence interval [CI] 0.54-1.57). After a median follow-up of 1397 [IQR 922.7-1723.5] days, JW patients were not associated with a significantly higher all-cause mortality (adjusted hazard ratio 0.77, 95% CI 0.24-2.42). Cardiac surgery can be safely performed in non-anemic JW patients despite the refusal of blood transfusions. Favorable clinical outcomes can be achieved by the use of specific perioperative strategies for bloodless surgery with no differences as compared to control patients except in JW patients with a very low level of post-operative hemoglobin not supported by immediate transfusions., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Purpose: Relatively few data are available on long-term survival and incidence of ventricular arrhythmias in cardiac resynchronization therapy (CRT) patients. We investigated long-term outcomes of CRT patients with non-ischemic dilated cardiomyopathy stratified as responders or non-responders according to radionuclide angiography., Methods: Fifty patients with non-ischemic dilated cardiomyopathy undergoing CRT were assessed by equilibrium Tc 99 radionuclide angiography with bicycle exercise at baseline and after 3 months. Intra- and interventricular dyssynchrony were derived by Fourier phase analysis. Patient clinical outcome was assessed after 10 years., Results: At 3 months, 50% of patients were identified as CRT responders according to an increase in LV ejection fraction ≥ 5%. During a follow-up of 109 ± 48 months, 30% of patients died and 6% underwent heart transplantation. Age and history of paroxysmal atrial fibrillation were found to be predictors of all-cause mortality. CRT responders showed lower risk of death from cardiac causes than non-responders. At follow-up, 38% of patients presented at least one episode of sustained ventricular tachycardia, with a similar percentage between responders and non-responders., Conclusion: At long-term follow-up, non-ischemic CRT recipients identified as responders by radionuclide angiography were found to be at lower risk of worsening heart failure death than non-responders. Long-term risk for sustained ventricular arrhythmia was similar between CRT responders and non-responders., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The 4S-AF scheme [Stroke risk, Symptom severity, Severity of atrial fibrillation (AF) burden, Substrate severity] was recently proposed to characterize AF patients. In this post hoc analysis we evaluated the agreement between the therapeutic strategy (rate or rhythm control, respectively), as suggested by the 4S-AF scheme, and the actual strategy followed in a patients cohort. Outcomes of interest were as follows: all-cause death, a composite of all-cause death/any thromboembolism/acute coronary syndrome, and a composite of all-cause death, any thrombotic/ischemic event, and major bleeding (net clinical outcome). We enrolled 615 patients: 60.5% male, median age 74 [interquartile range (IQR) 67-80] years; median CHA 2 DS 2 VASc 4 and median HAS-BLED 2. The 4S-AF score would have suggested a rhythm-control strategy in 351 (57.1%) patients while a rate control in 264 (42.9%). The strategy adopted was concordant with the 4S-AF suggestions in 342 (55.6%) cases, and non-concordant in 273 (44.4%). After a median follow-up of 941 days (IQR 365-1282), 113 (18.4%) patients died, 158 (25.7%) had an event of the composite endpoint. On adjusted Cox regression analysis, when 4S-AF score suggested rate control, disagreement with that suggestion was not associated with a worse outcome. When 4S-AF indicated rhythm control, disagreement was associated with a higher risk of all-cause death (HR 7.59; 95% CI 1.65-35.01), and of the composite outcome (HR 2.69; 95% CI 1.19-6.06). The 4S-AF scheme is a useful tool to comprehensively evaluate AF patients and aid the decision-making process. Disagreement with the rhythm control suggestion of the 4S-AF scheme was associated with adverse clinical outcomes., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Underweight or overweight patients with cardiovascular diseases are associated with different outcomes. However, the data on the relation between body mass index (BMI) and outcomes after transcatheter aortic valve implantation (TAVI) are not homogeneous. The aim of this study was to assess the role of low BMI on short and long-term mortality in real-world patients undergoing TAVI. We retrospectively included patients undergoing TAVI for severe aortic valve stenosis. Patients were classified into three BMI categories: underweight (< 20 kg/m 2 ), normal weight (20-24.9 kg/m 2 ) and overweight/obese (≥ 25 kg/m 2 ). Our primary endpoint was long-term all-cause mortality. The secondary endpoint was 30-day all-cause mortality. A total of 794 patients were included [mean age 82.3 ± 5.3, 53% females]. After a median follow-up of 2.2 years, all-cause mortality was 18.1%. Patients in the lowest BMI group showed a higher mortality rate as compared to those with higher BMI values. At the multivariate Cox regression analysis, as compared to the normal BMI group, BMI < 20 kg/m 2 was associated with long-term mortality independently of baseline risk factors and postprocedural adverse events (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.30-4.03] and HR 2.61, 95% CI 1.48-4.60, respectively). The highest BMI values were found to be protective for both short- and long-term mortality as compared to lower BMI values even after applying the same adjustments. In our cohort, BMI values under 20 kg/m 2 were independent predictors of increased long-term mortality. Conversely, the highest BMI values were associated with lower mortality rates both at short- and long-term follow-up., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Pericardial effusion can dangerously precipitate patient's hemodynamic stability and requires prompt intervention in case of tamponade. We investigated potential predictors of in-hospital mortality, a composite outcome of in-hospital mortality, pericardiocentesis-related complications, and the need for emergency cardiac surgery and all-cause mortality in patients undergoing percutaneous pericardiocentesis. This is an observational, retrospective, single-center study on patients undergoing percutaneous pericardiocentesis (2010-2019). We enrolled 81 consecutive patients. Median age was 71.4 years (interquartile range [IQR] 58.1-78.1 years) and 51 (63%) were male. Most of the pericardiocentesis were performed in an urgency setting (76.5%) for cardiac tamponade (77.8%). The most common etiology was idiopathic (33.3%) followed by neoplastic (22.2%). In-hospital mortality was 14.8% while mortality during follow-up (mean 17.1 months) was 44.4%. Only hemodynamic instability (i.e., cardiogenic shock, hypotension refractory to fluid challenge therapy and inotropes) was associated with in-hospital mortality at the univariate analysis (odds ratio [OR] 7.2; 95% confidence interval [CI] 1.76-29.4). Non-neoplastic/non-idiopathic etiology and hemodynamic instability were associated with the composite outcome of in-hospital mortality, need for emergency cardiac surgery, or pericardiocentesis-related complications (OR 5.75, 95% CI 1.65-20.01, and OR 5.81, 95% CI 2.11-15.97, respectively). Multivariate Cox regression analysis adjusted for possible confounding variables (age, coronary artery disease, and hemodynamic instability) showed that neoplastic etiology was independently associated with medium-term mortality (hazard ratio [HR] 4.05, 95% CI 1.45-11.36). In a real-world population treated with pericardiocentesis for pericardial effusion, in-hospital adverse outcomes and medium-term mortality are consistent, in particular for patients presenting with hemodynamic instability or neoplastic pericardial effusion., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Background: The aim of the present study was to compare clinical and electrocardiographic characteristics of patients with COVID-19 pneumonia in Modena, Emilia Romagna, Italy., Methods: Patients admitted to the emergency department for suspected COVID-19 pneumonia from March the 16th to April the 15th were enrolled in the study. COVID-19 pneumonia was confirmed by positive nasopharyngeal swab. Primary endpoint was 30-day mortality., Results: 201 patients were diagnosed with COVID-19 pneumonia. Compared to survivors, patients who died were older (79.7 ± 10.8 vs 65.6 ± 14.1, p < 0.001), with a more complex cardiovascular history, including coronary artery disease (CAD, 33.3% vs 13.3%, p = 0.004), atrial fibrillation (23.8 vs 8.8, p = 0.011) and chronic kidney disease (CKD 35.7% vs 7.0%, p < 0.001). 30-day mortality was 20,9% in these patients; atrial fibrillation (OR 12.74, 95% CI 3.65-44.48, p < 0.001), ST-segment depression (OR 5.30, 95% CI 1.50-18.81, p = 0.010) and QTc-interval prolongation (OR 3.17, 95% CI 1.24-8.10, p = 0.016) at ECG admission were associated to an increased mortality risk. On the contrary, sinus rhythm (OR 0.08, 95% CI 0.02-0.27, p < 0.001) and low-molecular weight heparin (LMWH) administration (OR 0.08, 95% CI 0.02-0.29, p < 0.001) were related to reduced mortality. At multivariate analysis, after adjustment for age, sex, diabetes, CAD, and MCA admission, sinus rhythm (HR 2.7, CI 95% 1.1-7.0, p = 0.038) and LMWH (HR 8.5, 95% CI 2.0-36.6, p = 0.004) were confirmed to be independent predictors of increased survival., Conclusion: Sinus rhythm at ECG admission in COVID-19 pneumonia patients was associated with greater survival as well as LMWH administration, which conferred an overall better outcome., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Atrial fibrillation (AF) may progress from a non-permanent to a permanent form, and improvement in prediction may help in decision-making. In- and outpatients with non-permanent AF were enrolled in a prospective study and followed every 6 months. At baseline, 314 out of 523 patients (60%) had non-permanent AF (25.5% paroxysmal AF, 52.5% persistent, 2% first diagnosed AF). They were mostly males (188, 59.9%), median age 71 years [interquartile range (IQ) 62-77], median CHA 2 DS 2 VASc 3 (IQ 1-4), median HATCH score 1 (IQ 1-2). During a follow-up of 701 (IQ 437-902) days, 66 patients (21%) developed permanent AF. CHA 2 DS 2 VASc and HATCH scores were incrementally associated with AF progression (p for trend CHA 2 DS 2 VASc < 0.001, HATCH p = 0.001). Cox multivariable proportional hazard regression analysis showed that age [hazard ratio (HR) 1.042; 95%CI 1.005-1.080; p = 0.025], moderate-severe left atrial (LA) enlargement at echo (HR 2.072, 95%CI, 1.121-3.831; p = 0.020), antiarrhythmics drugs (HR 0.087, 95%CI 0.011-0.659, p = 0.018), EHRA score > 2 (HR 0.358, 95%CI 0.162-0.791, p = 0.011) and valvular disease (HR 2.196, 95%CI 1.072-4.499, p = 0.032) were significantly associated with AF progression. Adding "moderate-severe LA dilation" to clinical scores, eg. HATCH score (HATCH-LA) with 2 points (Cox multivariable regression analysis) improved prediction of AF progression vs. HATCH score (p = 0.0225). In patients without permanent AF, progression of AF was independently associated with age, LA dilation, AF symptoms severity, antiarrhythmic drugs and valvular disease. Adding LA dilation (moderate-severe volume increase) to clinical scores improved prediction of progression to permanent AF., (© 2020. Società Italiana di Medicina Interna (SIMI).)

COVID-19 outbreak had a major impact on the organization of care in Italy, and a survey to evaluate provision of for arrhythmia during COVID-19 outbreak (March-April 2020) was launched. A total of 104 physicians from 84 Italian arrhythmia centres took part in the survey. The vast majority of participating centres (95.2%) reported a significant reduction in the number of elective pacemaker implantations during the outbreak period compared to the corresponding two months of year 2019 (50.0% of centres reported a reduction of > 50%). Similarly, 92.9% of participating centres reported a significant reduction in the number of implantable cardioverter-defibrillator (ICD) implantations for primary prevention, and 72.6% a significant reduction of ICD implantations for secondary prevention (> 50% in 65.5 and 44.0% of the centres, respectively). The majority of participating centres (77.4%) reported a significant reduction in the number of elective ablations (> 50% in 65.5% of the centres). Also the interventional procedures performed in an emergency setting, as well as acute management of atrial fibrillation had a marked reduction, thus leading to the conclusion that the impact of COVID-19 was disrupting the entire organization of health care, with a massive impact on the activities and procedures related to arrhythmia management in Italy.

Management of atrial fibrillation (AF) may be challenging in clinical practice. Given the complexity of AF patients and the continuous advances in AF clinical management, there is a need for standardized programmes aimed at collecting so-called 'real-world clinical practice data' regarding the epidemiology, diagnostic/therapeutic/management practices and assessing adherence to guidelines. Over the past 20 years, the number of registries and surveys based on real-world AF patients has been dramatically increased. In Europe, based on the Euro Heart Survey (EHS) and the EURObservational Research Programme (EORP), a large series of studies based on these prospective, observational, large-scale multicentre registries on AF have been published. This narrative review gives an overview of these two projects on AF led by the European Society of Cardiology, focusing mainly on the contribution that these studies have provided to AF management and patient outcomes. Both the EHS and the EORP registries have collected a large amount of data regarding contemporary clinical practice, and despite some limitations, mainly related to their observational nature, these registries have contributed to our knowledge and clinical management of AF patients.

The number of patients with cardiac implantable electronic devices (CIEDs) requiring radiation therapy (RT) for cancer treatment is increasing. The purpose of this study is to estimate the prevalence, possible predictors, and clinical impact of RT-related CIEDs malfunctions. We retrospectively reviewed the medical records of all pacemaker (PM)/implantable cardioverter-defibrillator (ICD) patients who underwent RT in the last 14 years. One hundred and twenty-seven patients who underwent 150 separate RT courses were analysed (99 with a PM and 27 with an ICD). Of note, 21/127 (16.6%) patients were PM-dependent. Neutron-producing RT was used in 37/139 (26.6%) courses, whereas non-neutron-producing RT was used in 102/139 (73.4%) courses. The cumulative dose (Dmax) delivered to the CIED exceeded 5 Gy only in 2/132 (1.5%) cases. Device malfunctions were observed in 3/150 (2%) RT courses, but none was life-threatening or led to a major clinical event and all were resolved by CIED reprogramming. In all cases, the Dmax delivered to the CIED was < 2 Gy. Two malfunctions occurred in the 37 patients treated with neutron-producing RT (5.4%), and 1 malfunction occurred in the 102 patients treated with non-neutron-producing RT (1%) (p = 0.17). Device relocation from the RT field was performed in 2/127 (1.6%) patients. RT in patients with CIED is substantially safe if performed in an appropriately organized environment, with uncommon CIEDs malfunctions and no major clinical events. Neutron-producing energies, rather than Dmax, seem to increase the risk of malfunctions. Device interrogation on a regular basis is advised to promptly manage CIED malfunctions.

The frequency of premature atrial complexes (PACs) has been related with atrial fibrillation (AF) occurrence and adverse prognosis. Research objective was to evaluate whether temporal patterns of PACs are directly associated with AF onset in pacemaker patients with continuous monitoring of the atrial rhythm. Overall, 193 pacemaker patients (49% female, 72 ± 9 years old), enrolled in a national registry, were analyzed. Frequency of daily PACs was measured in a 14-day initial observation period, during which patients were in sinus rhythm. In the following period, temporal occurrence and frequency of daily PACs and eventual onset of AF were derived by pacemaker diagnostics. In the run-in period, median PACs frequency was 614 PACs/day (interquartile range 70-3056). Subsequently, in a median follow-up of 6 months, AF occurred in 109 patients, in particular in 37/96 (38.5%) patients with a PAC rate < 614 PACs/day and in 72/97 (74.2%) patients with PAC rate ≥ 614 PACs/day (p < 0.001). In patients with AF occurrence, the number of daily PACs, normalized by dividing for the average of PACs in ten preceding days, progressively increased in the 5 days preceding AF. Cox model predictive analysis showed that the risk of AF was significantly higher in patients with a relative increase of the daily PACs higher than 30% compared with PACs average number in ten preceding days [hazard ratio (95% confidence interval) 3.67 (2.40-5.59), p < 0.001]. PACs frequency increases in the 5 days preceding AF onset. A relative increase of the daily PACs is significantly associated with the risk of AF occurrence.

Aim: We carried out this study to investigate mid-term effects of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and neurohormonal response, expressed by N-terminal pro-brain natriuretic peptide (NT-proBNP), in heart failure patients stratified by baseline RV ejection fraction (RVEF)., Methods and Results: Thirty-six patients with nonischemic dilated cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. Plasma NT proBNP was assessed before implantation and after 3 months. At baseline, RVEF was impaired (≤35%) in 14 patients, preserved (>35%) in 22. At 3 months, RVEF improved during rest and exercise (P = .02) in patients with impaired RV function, while remaining unchanged in patients with preserved RV function. Rest and exercise RV dyssynchrony decreased in both groups at follow-up (P < .05). A similar mid-term improvement in left ventricular (LV) function and NT-proBNP was observed in patients with impaired and preserved RVEF. In the former, the decrease in NT-proBNP correlated with the improvements both in LV and RV dyssynchrony and functions., Conclusion: CRT may improve RV performance, during rest and exercise, and neurohormonal response in heart failure patients with nonischemic dilated cardiomyopathy and baseline RV dysfunction. RV dysfunction should not be considered per se a primary criterion for excluding candidacy to CRT.

Prescription of non-vitamin K antagonist oral anticoagulants (NOACs) requires an assessment of renal function (RF) and the Cockcroft-Gault (CG) equation is traditionally recommended. The objective of the study was to evaluate the potential changes in NOACs management using different equations for estimating RF. In a post hoc analysis of a prospective cohort of patients with atrial fibrillation, we considered different equations: (1) CG for creatinine clearance (CrCl), (2) modification of diet in renal disease (MDRD), (3) CKD-EPI, (4) Berlin Initiative Study 1 (BIS-1) and (5) full age spectrum (FAS), for glomerular filtration rate (GFR). RF was classified according to CrCl in three categories: severely depressed (SD-RF) < 30 ml/min; moderately depressed (MD-RF) 30-49 ml/min; preserved/mildly depressed (P-RF) ≥ 50 ml/min. Concordances in the assignments were analyzed. A population of 402 patients (61.2% males, age 72 ± 11) was categorized according to CrCl: 12 patients (2.9%) as SD-RF, 81 (20.1%) as MD-RF, 309 (76.8%) as P-RF. A potential change in NOACs management could occur using GFR equations rather than CrCl in 16.9% of patients using MDRD formula, in 11.7% using BIS-1, in 14.7% using CKD-EPI and in 12.9% using the FAS equation. Important changes in RF estimates were more frequent in patients aged ≥ 75, but also BMI had a meaningful impact. Use of equations estimating GFR instead of the Cockcroft-Gault equation may result in changes in NOACs management in 12-17% of patients. In the elderly ≥ 75, more pronounced changes in RF classification are detectable according to different equations and NOACs dosing should be further investigated.

Purpose: After regulatory restrictions for terfenadine and astemizole in '90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines., Methods: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997-2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression., Results: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6-7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7-7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1-14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1-10.8) and PHARMO (ORadj, 4.6; 1.3-16.2)., Conclusions: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile.

Purpose: Oncological patients are at increasing risk of QT prolongation, a risk factor for ventricular arrhythmia. We assessed impact and risk factors for corrected QT (QTc) prolongation during multiple-cycle chemotherapy., Methods: We enrolled 100 outpatients initiating chemotherapy in a university center specializing in female cancer. Clinical, drug, laboratory, and 12-lead ECG data collection at baseline and at each chemotherapy cycle was performed., Results: Enrolled patients were followed for 992 chemotherapy cycles (median 7; interquartile range 6-13); 2438 ECGs were recorded (20; 18-31) 36.8% pre-therapy, 36.8% following chemotherapy, and 22.5% 7-10 days after chemotherapy. Maximum QTc (Max-QTc) was recorded after 4 chemotherapy administrations in >50% of the entire cohort and also within every subset of patients with prolonged QTc (57% 471-480 ms; 54% 481-500 ms; 66% >500 ms). No cumulative effect on QTc was shown. QTc prolongation was comparable among the various protocols. Prophylactic/supportive drugs were not associated with additional QTc prolongation. Variables independently associated with QTc prolongation >470 ms were age (OR 1.056 95% CI 1.006-1.108, p = 0.028) and the baseline-first chemotherapy averaged QTc (BC-QTc) (OR 1.092 95% CI 1.051-1.136), a novel parameter devised for this study. Only BC-QTc maintained significance for QTc >480 ms. BC-QTc >435 ms identified 100 % of patients with Max-QTc >500 ms, 96% with Max-QTc 481-500 ms, and 66% with Max-QTc 471-480 ms. Only 29% of patients with Max-QTc ≤470 ms presented a BC-QTc >435 ms., Conclusions: Our results confirm the high prevalence of QTc prolongation after chemotherapy. Most of the patients reached Max-QTc after several cycles. BC-QTc may help in stratifying arrhythmic risk in real-world clinical practice.

Purpose: Quadripolar left ventricular (LV) leads allow for several pacing configurations in candidates for cardiac resynchronization therapy (CRT). Whether different pacing configurations may affect LV dyssynchrony and systolic function is not completely known. We aimed to evaluate the acute effects of different pacing vectors on LV electromechanical parameters in patients implanted with a quadripolar LV lead., Methods: In this two-centre study, within 1 month of implantation 21 CRT patients (65 ± 8 years, 76 % men, 38 % ischemic) receiving a quadripolar LV lead (Quartet 1458Q, St Jude Medical) underwent LV capture threshold assessment, intracardiac electrogram optimization, and two-dimensional echocardiography during four pacing configurations: D1-P4, P4-RV coil, D1-RV coil, and P4-M2. LV dyssynchrony and contractile function were expressed by septal-to-lateral delay and global longitudinal strain (GLS)., Results: LV capture threshold varied between the configurations (P < 0.001), showing higher values in the configurations P4-RV coil and P4-M2. Septal-to-lateral delay decreased in the configurations D1-P4 and D1-RV coil (P = 0.003 and P = 0.033 vs. spontaneous rhythm, respectively). GLS improved significantly vs. spontaneous rhythm only in the configuration D1-P4 (from -8.6 ± 3.5 to -11.0 ± 3.2 %, P = 0.001). Accordingly, an increase in stroke volume and a decrease in mitral regurgitation were observed in the configuration D1-P4 (P ≤ 0.001 vs. spontaneous rhythm)., Conclusions: In CRT patients receiving a quadripolar LV lead, significant variations in electromechanical parameters were observed by changing pacing vector. Individually targeting the optimal pacing site may enhance the acute haemodynamic response to CRT.

Purpose: Our aim was to evaluate whether dronedarone authorization impacts antiarrhythmic drug prescribing in Sweden and Emilia Romagna (Italy)., Methods: Prescriptions of classes I and III antiarrhythmics, expressed as defined daily doses per thousand inhabitants per day (DDD/TID) were monthly using information collected from pharmacy-reimbursed databases. Interrupted time series analysis was applied to compare prescription data over the 2009-2011 period., Results: In Emilia Romagna, the overall consumption of antiarrhythmics was six times as high as in Sweden (7.6 vs. 1.2 DDD/TID). In the first year on the market, dronedarone represented 1.0 % in Italy and 10.7 % in Sweden of the overall antiarrhythmic prescriptions. In Sweden, dronedarone authorization generated an increase in the prescription trend of antiarrhythmics (trend change +0.02; p < 0.001) without variation in amiodarone use In Emilia Romagna, dronedarone marketing did not influence the prescription pattern of either overall antiarrhythmics or amiodarone., Conclusions: Emilia Romagna and Sweden substantially differ in terms of overall antiarrhythmic use. Although clinical guidelines place dronedarone among first-choice treatments for atrial fibrillation, amiodarone prescribing was not affected in either country by the entry of dronedarone, probably due to a cautious approach by clinicians in line with regulatory recommendations and safety warnings.

Telecardiology may help confront the growing burden of monitoring the reliability of implantable defibrillators/pacemakers. Herein, we suggest that the evolving capabilities of implanted devices to monitor patients' status (heart rhythm, fluid overload, right ventricular pressure, oximetry, etc.) may imply a shift from strictly device-centered follow-up to perspectives centered on the patient (and patient-device interactions). Such approaches could provide improvements in health care delivery and clinical outcomes, especially in the field of heart failure. Major professional, policy, and ethical issues will have to be overcome to enable real-world implementation. This challenge may be relevant for the evolution of our health care systems.

Considering the relatively short history of cardiac resynchronization therapy (CRT), the amount of available evidence of efficacy is impressive, and effectiveness studies are now required. Transfer of our experimentally gained knowledge into the real world raises issues that call for synchronization among the many specialists involved in chronic heart failure (CHF) management and CRT decision making. From an economic perspective, the demonstrated ability of CRT to reduce hospitalizations could help ease the burden on health systems derived from the growing incidence of CHF. Recent American College of Cardiology/American Heart Association guideline revisions should encourage a synchronized approach to rational deployment of CRT in selected patients. Nevertheless, current QRS criteria for CRT candidacy do not directly address the key issue of identification of patients with a pacing-correctable mechanical dyssynchrony (and in clinical trials, 25-30% of implanted patients did not respond to CRT). Echocardiography could become an important adjunct (or even an alternative) to QRS duration for patient selection; routine implementation would require use of straightforward, reproducible measurements, possibly obtainable on standard equipment. Echocardiography could also help optimize site location, although this would not eliminate lead placement problems. A series of issues remain open for investigation, including the potential of CRT in patients with atrial fibrillation, impact of devices with defibrillation ability, effects of electrical/pharmacological tailoring, need for confirmation that efficacy of CRT extends into the long term and possible use of CRT in mild CHF. Interdisciplinary synchronization in the various phases of CRT (screening, proposing, implementing, optimizing and monitoring) should eventually help develop a coordinated system for patient referral.

Introduction: Atrial tachyarrhythmias are a common co-morbidity in patients with an ICD indication. Recently introduced ICD's are equipped to independently detect and treat atrial and ventricular tachyarrhythmias. The purpose of this prospective study was to evaluate the incidence and termination of spontaneous atrial and ventricular tachyarrythmias in patients with a history of atrial tachyarrhythmias., Methods and Results: Ninety patients, 70% male with an ICD indication and history of atrial tachyarrhythmia (LVEF 45 +/- 6%, [AT/AF indication 55 +/- 10, AT/VT 45 +/- 16], 46% CAD) were enrolled and 89 were implanted with a VENTAK PRIZM AVT (Guidant). Spontaneous atrial and ventricular tachyarrhythmias were printed and evaluated during an average follow-up period of 272 +/- 72 days utilizing the stored intracardial electrogram function of the device. Nineteen patients (21%) presented had only atrial tachyarrhythmias, 32 patients (36%) had both atrial and ventricular tachyarrhythmias and 18 patients (20%) had only ventricular tachyarrhythmias. Patients with only atrial tachyarrhythmias had a total of 3274 atrial episodes; 2002 terminated spontaneously, 1264 were treated with ATP and 8 with shock therapy. ATP was successful in 735 (58%) of 1264 episodes. Patients with both atrial and ventricular tachyarrhythmias had 7277 documented atrial tachyarrhythmias, 5231 terminated spontaneously, 1153 of 2009 were terminated by ATP (57.4%) and 37 by shock therapy (20 patient controlled). Atrial tachyarrhythmias identified as atrial flutter (AT) by the atrial rhythm classification (ARC) algorithm had a higher ATP conversion success rate than episodes identified as atrial fibrillation (AF); 66.7% for AT and 26.4% for AF. Patients with only ventricular tachyarrhythmias had 690 documented episodes, 401 terminated spontaneously, 248 (85.8%) were terminated by ATP and 41 by shock., Conclusion: Seventy-seven percent of patients with an ICD indication had spontaneous atrial and/or ventricular tachyharrhythmias within the first 6 months after ICD implantation. ATP therapy terminated 58% of all atrial tachyarrhytmias and 66.7% of the atrial flutters. The dual chamber ICD detected, classified and terminated all ventricular tacharrhythmias appropriately.

Background: The effect of left ventricular (LV) systolic function on the long-term left ventricular pacing and sensing threshold is unclear., Methods and Results: We studied the effect of LV ejection fraction (LVEF) on the LV pacing and sensing threshold in 56 patients (mean age: 70.2 +/- 10.5 years) underwent permanent LV pacing using a self-retaining coronary sinus lead (Model 1055 K, St Jude Medical, USA). In 49 patients, the LV lead was implanted for conventional pacemaker indication (sick sinus syndrome = 14, heart block = 26 or slow atrial fibrillation = 9). The remaining 7 patients were implanted for congestive heart failure. The LV pacing and sensing threshold, and lead impedance were compared between patients with LVEF <40% (Group 1, n = 28) and LVEF >40% (Group 2, n = 28) during implant and at 3-month follow up. The LV pacing lead was successfully implanted in all patients without any lead dislodgement on follow-up. At implant, Group 1 patients had a significant lower R wave amplitude, but similar LV pacing threshold and lead impedance as compared to Group 2. However, at 3-month follow-up, Group 1 patients had a significantly higher LV pacing threshold compared to Group 2 patients. There were no significant differences in the sensing threshold and lead impedance between the two groups. Furthermore, there was also a significant interval increase in LV pacing threshold in Group 1 patients (0.94 +/- 0.12 V) after 3 months, but not in Group 2 patients (0.16 +/- 0.08 V, p < 0.01)., Conclusions: The results of this study suggest that the LV systolic function has a significant impact on the long-term LV pacing threshold. The long-term left ventricular pacing threshold in patients with left ventricular systolic dysfunction increased after implant and was higher than patients with normal left ventricular systolic function.

Objective: To assess the haemodynamic effects of short-term treatment with dofetilide in comparison with sotalol in patients with ischaemic heart disease., Methods: Twelve patients with ischaemic heart disease and sustained ventricular tachycardia were treated with dofetilide [500 microg twice daily (b.i.d.)] or sotalol (160 mg b.i.d., randomised sequence separated by wash-out period) for 3-5 days. Right-heart catheterisation was performed at baseline and at the end of each short-term treatment phase., Results: The main findings were a significant reduction in heart rate, mean systemic pressure and cardiac index (-13%) during treatment with sotalol. Conversely, cardiac index increased significantly during dofetilide (mean percentage change 11%) with no effect on heart rate and systemic blood pressure., Conclusions: Oral dofetilide exerts favourable haemodynamic effects in comparison with D,L-sotalol following short-term oral treatment. In view of these observations, the use of dofetilide may be proposed also in patients with ventricular tachyarrhythmias associated with impaired left-ventricular function. Whether the haemodynamic differences between dofetilide and D,L-sotalol are the basis for differences in tolerability remains to be evaluated.

Aim of the Study: The Consistent Atrial Pacing (CAP) algorithm has been designed to achieve a high percentage of atrial pacing to suppress paroxysmal atrial fibrillation. The aim of our study was to compare the impact of DDDR+CAP versus DDDR pacing on paroxysmal atrial fibrillation recurrences and triggers in patients with Brady-Tachy Syndrome., Methods: 61 patients, 23 M and 38 F, mean age 75+/-9 y, affected by Brady-Tachy Syndrome, implanted with a DDDR pacemaker, were randomized to DDDR or DDDR+CAP pacing with cross over of pacing modality after 1 month., Results: 78 % of patients in DDDR pacing and 73 % in DDDR + CAP pacing (p=n.s.) were free from symptomatic paroxysmal atrial fibrillation recurrences. During DDDR+CAP pacing, the atrial pacing percentage increased from 77+/-29 % to 96+/-7 % (p<0.0001). Automatic mode switch episodes/day were 0.73+/-1.09 in DDDR and 0.79+/-1.14 (p=n.s.) in DDDR+CAP. In patients with less than 50 % of atrial pacing during DDDR, automaticmode switch episodes/day decreased during DDDR+CAP from 1.13+/-1.59 to 0.23+/-0.32 (p<0.05) and in patients with less than 90 % from 1.23+/-1.27 to 0.75+/-1.10 (p<0.001). The number of premature atrial complexes per day decreased during DDDR + CAP from 2665+/-4468 to 556+/-704 (p<0.02)., Conclusion: CAP algorithm allowed continuous overdrive atrial pacing without major side effects. Triggers of paroxysmal atrial fibrillation induction, such as premature atrial complexes, were critically decreased. Paroxysmal atrial fibrillation episodes were reduced in patients with atrial pacing percentage lower than 90 % during DDDR pacing.

The pharmacokinetics of flecainide has been studied in 12 patients with ventricular arrhythmias, both after single administration and during chronic treatment. Both the half-life and the AUC were significantly increased during chronic treatment. This suggests that the kinetics of flecainide might be non-linear also in patients with normal kidney and liver function. The increase in plasma flecainide levels during chronic treatment could not be predicted, so close monitoring of its plasma levels is advisable.