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Background: Prolonged QTc intervals and life-threatening arrhythmias (LTA) are potential drug-induced complications previously reported with antimalarials, antivirals, and antibiotics. Our objective was to evaluate the prevalence and predictors of QTc interval prolongation and incidences of LTA during hospitalization for coronavirus disease 2019 (COVID-19) among patients with normal admission QTc., Methods: We enrolled 110 consecutive patients in a multicenter international registry. A 12-lead electrocardiograph was performed at admission, after 7, and at 14 days; QTc values were analyzed., Results: After 7 days, 15 (14%) patients developed a prolonged QTc (pQTc; mean QTc increase 66 ± 20 msec; +16%; P < .001); these patients were older and had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, and lower platelet counts. The QTc increase was inversely proportional to the baseline QTc level and leukocyte count and directly proportional to the basal heart rate (P < .01).We conducted a multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate, and dual antiviral therapy; age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; P < .05), basal heart rate (OR, 1.07; 95% CI, 1.02-1.13; P < .01), and dual antiviral therapy (OR, 12.46; 95% CI, 2.09-74.20; P < .1) were independent predictors of QT prolongation.The incidence rate of LTA during hospitalization was 3.6%. There was 1 patient who experienced cardiac arrest and 3 with nonsustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of the mortality rate., Conclusions: After 7 days of hospitalization, 14% of patients with COVID-19 developed pQTc; age, basal heart rate, and dual antiviral therapy were found to be independent predictors of pQTc. Life-threatening arrhythmias have an incidence rate of 3.6%, and were associated with a poor outcome., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The venous access for the insertion of permanent leads of cardiac implantable electronic devices is often achieved by venous cutdown of the cephalic vein, or by "blind" puncture of the subclavian vein using anatomical landmarks, or by fluoroscopy-assisted methods., Methods: We have retrospectively analyzed our clinical experience to verify the feasibility, the safety, and efficacy of the adoption of ultrasound-guided puncture/cannulation of the axillary vein for this purpose., Results: Nine hundred eighty-seven leads were placed during 548 consecutive procedures, accessing the axillary vein in the infraclavicular area using real-time ultrasound guidance. Venipuncture was successful in 99.8% of cases. The access time was 11 seconds (range 4-580). We recorded three cases of pneumothorax (0.5%), but no hemothorax and no hemo-mediastinum. The incidence of local hematoma was 2.1% (12 cases). No injury to the brachial plexus or to the phrenic nerve was recorded. In a follow-up of 33 months (range 16-39), we observed no cases of "subclavian crush syndrome" (damage of the leads at the level of the thoracic inlet), and the rate of pocket infection/infective endocarditis was 0.7%., Conclusion: In our experience, ultrasound-guided puncture/cannulation of the axillary vein for implantation of permanent leads is feasible, effective, and safe. It might be considered as a first option for this procedure., (© 2020 Wiley Periodicals LLC.)

Background and Aims: Systemic inflammation has been hypothesized as a possible mechanism of Takotsubo cardiomyopathy (TTC). Aim of the study was to assess the role of interleukin (IL)-6 and IL-10 in subjects with an episode of TTC., Methods: Fifty-six consecutive subjects with TTC were prospectively enrolled in the study and followed for a mean of 178 days. Circulating levels of IL-6, IL-10, clinical condition and left ventricular ejection fraction were evaluated at admission. Incidence of death, re-hospitalization and recurrence of TTC during follow-up was also recorded., Results: 23% of patients experienced in-hospital complications while 20% of patients had adverse events at follow-up. IL-6 and IL-10 serum levels at admission were higher in subjects with adverse events at follow-up (120 ± 294 vs. 22 ± 40 pg/ml, p<0.05; 13 ± 35 vs. 2 ± 3 pg/ml, p=0.05, respectively). Increased serum levels of IL-6 and IL-10 were associated with higher adverse events rates at follow-up (Log-Rank p<0.001, <0.05, hazard ratio 8.6, 5.1, respectively) and mortality rates (Log-Rank p<0.001, p<0.05, hazard ratio 20.8, 7.1, respectively). Subjects with both increased IL-6 and IL-10 levels were characterized by an increased risk of adverse events when compared to subjects with only IL-6 or IL-10 increased levels or with values below cutoff values (Log-Rank p<0.01 for any event, <0.001 for death; hazard ratio 1.20 for any event, 1.31 for death), even after correction for age, LVEF and NTproBNP levels in multivariable Cox analysis., Conclusions: Serum IL-6 and IL-10 admission levels are associated with higher risk of adverse events during follow-up., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study is to evaluate the possible role of carbohydrate-antigen(CA)-125 as prognostic marker at short- and long-term follow-up, in subjects with Takotsubo cardiomyopathy (TTC). Sixty-three consecutive subjects with TTC were enrolled in the study and followed for a median 139 days. Circulating levels of CA-125, NT-proBNP, and left ventricular ejection fraction (LVEF) were evaluated at admission. Duration of hospital stay, incidence of death, re-hospitalization and recurrence of TTC during follow-up were recorded. The mean hospital stay was 8.3 days, adverse events occurred during follow up in 17 % of cases. CA-125 levels at admission are inversely related to LVEF (r -0.30, p < 0.05) and directly related to hospital stay (r 0.29, p < 0.05). CA-125 levels at admission are higher in subjects with adverse events at follow-up (88.9 ± 200.0 vs 20.9 ± 30.0 U/mL, p < 0.05). Rates of incidence of adverse events are proportionally increased with CA-125 tertiles (0, 6, 11 % respectively, p for trend <0.01), at survival analysis (Log Rank p < 0.05) and after correction for age, gender, LVEF and NT-proBNP levels in multivariable Cox analysis (p < 0.05). CA-125 levels <10 U/ml are predictors of adverse events at follow up with 91 % sensitivity, 52 % specificity, 29 % positive predictive power, and 96 % negative predictive power. Increased CA-125 admission levels are associated with a longer hospital stay, a lower LVEF, and a higher risk of adverse events during follow up. CA-125 might be useful for early risk stratification of subjects with TTC.

Background: Left ventricular outflow tract obstruction (LVOTO) may complicate an episode of Takotsubo cardiomyopathy (TTC), potentially leading to cardiogenic shock. Beta-blockers are considered the most suitable treatment for such complication., Aim of the Study: The objective of this study was to evaluate the hemodynamic effects, safety, and feasibility of a selective beta-blocker (β1) with a short half-life, esmolol, in subjects with a TTC episode., Methods: Ninety-six consecutive patients with TTC were enrolled in a multicenter registry. The hemodynamic and echocardiographic effects of esmolol (0.15-0.3 mg/kg/min) were analyzed in nine consecutive patients with LVOTO. Clinical course of patients, hemodynamics, days of hospitalization, LV function, and adverse events at follow-up were recorded., Results: Left ventricular outflow tract obstruction was present in 10 (10.4%) of 96 patients. Patients with LVOTO were older and had higher values of troponin-I at admission. LV ejection fraction at admission (36.1 ± 8.4%) significantly improved at discharge (51.4 ± 6.9%, P = 0.001). Among patients treated with esmolol infusion, LVOT pressure gradient before treatment was 47.6 ± 16.6 mmHg and after 18.2 ± 2.3 mmHg (P = 0.0091). Systolic blood pressure decreased from 123.8 ± 29.1 to 112.6 ± 12.7 mmHg (P = 0.1537). Mean hospital stay was 9 ± 2 days. No adverse events were observed during hospitalization and at follow-up., Conclusions: Esmolol infusion was temporally associated with reduction in intraventricular gradient and systemic blood pressure in patients with TTC and LVOTO. Further controlled studies are warranted to confirm these preliminary findings., (© 2016 John Wiley & Sons Ltd.)

Objectives: The objectives were to ascertain the prevalence of renal impairment among patients with a takotsubo cardiomyopathy (TTC) episode and whether clinical outcomes are related to renal function., Methods: A total of 108 consecutive subjects with TTC were enrolled in a multicenter registry and followed for a mean period of 429 days. Renal function was evaluated during hospitalization in terms of acute kidney injury/failure and estimated glomerular filtration rate (eGFR). Incidence of death, rehospitalization, and recurrence of TTC during follow-up was recorded., Results: Raised creatinine levels can be found during hospitalizations for TTC episodes (analysis of variance P<.001). Incidence of acute kidney injury was 10%; that of acute kidney failure was 1%. Admission eGFR levels were proportional to the duration of hospitalization (r = -0.28, P<.01). Estimated GFR nadir values were related to adverse events at follow-up (log-rank P<.001). The hazard ratio of adverse events at follow-up in subjects with severe renal impairment (nadir eGFR <30 mL/[min 1.73 m(2)]) vs those with eGFR >60 mL/(min 1.73 m(2)) was 1.817 (95% confidence interval, 1.097-3.009; P<.05)., Conclusions: Raised creatinine levels and impaired renal function may be found in patients with TTC. Lower eGFR values during hospitalization are associated with longer hospitalizations and higher rates of adverse events at follow-up. Renal function during a TTC episode should be carefully evaluated., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Tissue Doppler imaging (TDI) may be useful in identifying subjects at higher risk among patients with chronic heart failure (CHF). The clinical role of newly developed TDI parameters, however, still needs to be documented., Methods: A total of 287 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and were followed prospectively for a median 255 (204-316) days. Conventional echocardiography and TDI parameters were calculated. We also quantified by TDI a combined index (EAS index) of diastolic and systolic performance E'/(A'xS') and assessed its possible additional prognostic role in combination with 'traditional' parameters such as left ventricular ejection fraction (LVEF) and myocardial performance index (MPI)., Results: Subjects readmitted for worsening HF were characterized by higher levels of EAS index (median 0·14 (95% C.I. 0·12-0·21) vs. 0·11 (0·10-0·12, P < 0·05)). Increased rates of rehospitalization were found in subjects with EAS index >median (0·115) (21% vs. 10%, P < 0·05); higher EAS index values predicted the incidence of readmissions for worsening HF during follow-up, even at multivariable analysis. The assessment of EAS index in addition to LVEF and MPI showed an adjunctive prognostic value (log-rank P < 0·001 and P < 0·05, respectively)., Conclusions: EAS index assessed by TDI may be helpful in predicting the risk of rehospitalizations in subjects with CHF. EAS index may represent an independent adjunctive tool for the risk stratification of patients with CHF in addition to 'traditional' tools such as LVEF or MPI., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Efficacy of chronic drug therapy in prevention of stress-induced cardiomyopathy recurrences is not well established. We therefore aimed to evaluate in this meta-analysis whether pharmacological treatment can effectively prevent takotsubo cardiomyopathy (TTC) recurrences, according to available studies., Hypothesis: There is no evidence for preventing TTC recurrence by drug therapy., Methods: After a PubMed search, we conducted a meta-analysis of available studies (clinical nonrandomized registries) on efficacy of drug therapy in preventing recurrence of TTC., Results: A total of 23 (4.5%) TTC recurrences occurred in the 511 patients included in the analysis. Seven studies on the effects of β-blockers on prevention of TTC recurrence were evaluated; the odds ratio (OR) was 0.44 and the 95% confidence interval (CI) was 0.15-1.31. In 5 studies on the effects of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, the OR was 0.42 and the 95% CI was 0.08-2.36; in 3 studies on statins, the OR was 0.74 and the 95% CI was 0.07-7.3; and in 4 studies on aspirin, the OR was 0.33 with a 95% CI of 0.05-2.17 (P value not significant in all cases)., Conclusions: A meta-analysis of the efficacy of different medications through the clinical TTC registries available showed no clinical evidence for a standard drug treatment in the chronic management of TTC. β-Blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins, and aspirin do not seem to significantly reduce recurrences of TTC. Randomized, adequately powered studies are needed to further assess this issue., (© 2014 Wiley Periodicals, Inc.)

Objective: To evaluate the preoperative presence of C-reactive protein (CRP) and troponin T(hs-TnT) in patients with coronary artery disease (CAD) undergoing cardiopulmonary bypass (CPB) in order to better clarify the role of atrial inflammation and/or myocardial ischemia in the development of postoperative atrial fibrillation (POAF)., Design: Prospective, nonrandomized study., Setting: University hospital., Participants: Thirty-eight consecutive ischemic patients admitted to the authors' hospital for CAD undergoing elective on-pump coronary artery bypass grafting (CABG)., Intervention: Elective on-pump CABG., Measurements and Main Results: Peripheral blood samples were collected from all patients before and 24 hours after CABG to assess high sensitive (hs)-CRP and troponin T (hs-TnT) levels. The patients' heart rhythm was monitored by continuous ECG telemetry. Biopsies from the right atrial appendage were obtained at the beginning of the CABG procedure in order to perform immunohistochemistry for CRP and reverse transcription polymerase chain reaction for CRP mRNA expression. Fourteen patients out of 38 (36%) developed POAF. Atrial CRP was found in 31 patients (82%), 10 with POAF and 21 with sinus rhythm (71% v 87% respectively, p = ns). None of the atrial samples was positive for CRP mRNA. Atrial CRP did not correlate with serum hs-CRP levels and with occurrence of POAF, but with the incidence of diabetes (p = 0.010). Postoperative hs-TnT levels, but not hs-CRP levels, were identified as the only predictor of POAF occurrence (p = 0.016)., Conclusions: In patients undergoing CABG, neither peripheral nor tissue preoperative CRP levels, but only postoperative hs-TnT levels, correlated with POAF, suggesting the primary role of an ischemic trigger of atrial fibrillation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Tissue Doppler imaging (TDI) may be useful in identifying subjects at higher risk among patients with chronic heart failure (CHF). The clinical role of new developed TDI parameters, however, still needs to be documented., Methods: A total of 113 consecutive patients with CHF enrolled in the Daunia heart failure registry underwent echocardiography assessment and were followed prospectively for 234 ± 262 days. Conventional echocardiography and TDI parameters were calculated. We also calculated peak myocardial acceleration during isovolumic relaxation time (pIVA[r]) derived from TDI (pIVV(r)/AT)., Results: Subjects readmitted for worsening HF were characterized by lower levels of pIVA(r) (0.8 ± 0.3 vs. 1.3 ± 0.5 m/s(2) , P < 0.001). pIVA(r) levels predicted the incidence of readmission for worsening HF during follow-up (HR 0.78, 95% confidence interval 0.64-0.96, P < 0.05), even after multivariable analysis. The assessment of pIVA(r) in addition to left ventricular ejection fraction (LVEF) and E/E' provided additional prognostic value (Log Rank P < 0.05). The presence of abnormal pIVA(r), LVEF, and E/E' levels identified subjects with a higher risk of hospitalization for worsening dyspnea during follow-up than those with 2 abnormal marker levels or 0-1 (Log Rank P < 0.05)., Conclusions: Peak myocardial acceleration during isovolumic relaxation time may represent an independent adjunctive tool for the risk stratification of patients with CHF., (© 2013, Wiley Periodicals, Inc.)

Tako-Tsubo cardiomyopathy (TTC), is defined as a fully reversible acute deterioration of left-ventricular (LV) function, which is mainly found in women after an episode of emotional or physical stress (e.g. psychosocial stress, sepsis, surgery). The underlying mechanisms remain unclear. There is evidence suggesting a possible link between neurological disease and TTC. The pathophysiology of the several neurologic diseases has been reviewed searching for possible mechanisms that could lead to TTC in these patients., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Few works have evaluated the effect of statins on left ventricular dysfunction in patients with chronic heart failure (CHF), by using tissue Doppler imaging (TDI). We therefore aimed to investigate whether atorvastatin treatment may influence prognosis and myocardial performance evaluated by TDI in subjects with CHF., Methods: Five hundred thirty-two consecutive CHF outpatients enrolled in a local registry, the Daunia Heart Failure Registry, were prospectively analysed. 195 patients with CHF and left ventricular ejection fraction (LVEF) ≤40 %, either in treatment with atorvastatin (N: 114) or without statins (N: 81), underwent TDI examination. Adverse events were evaluated during follow-up., Results: The atorvastatin group showed a lower incidence of adverse events (cardiac death: 0 % vs 7 %, p < 0.01), and better TDI performance (E/E' 15 ± 5.7 vs 18 ± 8.3, p < 001) than controls. Ischaemic CHF patients in treatment with atorvastatin also showed a lower incidence of adverse events (death: 10 % vs 26 %, p < 0.05; sustained ventricular arrhythmias: 5 % vs 19 %, p < 0.05, cardiac death: 0 vs 8 %, p < 0.05) and better TDI performance (E/E' ratio: 15.00 ± 5.68 vs 19.72 ± 9.14, p < 0.01; St: 353.70 ± 48.96 vs 303.33 ± 68.52 msec, p < 0.01) than controls. The association between atorvastatin and lower rates of cardiac death remained statistically significant even after correction in a multivariable analysis (RR 0.83, 95 % CI 0.71-0.96, p < 0.05 in CHF with LVEF ≤40 %; RR 0.77, 95 % CI 0.62-0.95, p < 0.05 in ischaemic CHF with LVEF ≤40 %)., Conclusions: Treatment with atorvastatin in outpatients with systolic CHF is associated with fewer cardiac deaths, and a better left ventricular performance, as assessed by TDI.

Background: Patients with chronic heart failure (HF) are often rehospitalized; rehospitalization identifies subjects with a poorer quality of life and a worse prognosis. Estimates of the time intervals by tissue Doppler imaging (TDI) in patients with chronic HF has not been fully investigated, despite recent studies having explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as HF. We, therefore, aimed to assess the prognostic value of time intervals evaluated by TDI in patients with chronic HF., Methods: A total of 249 patients with chronic HF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and were followed prospectively for a mean 284 ± 210 days. Conventional echocardiography and TDI parameters were calculated; time intervals were calculated by TDI: ST (systolic time), ET (ejection time), FT (filling time), and ICT (isovolumic contraction time). We also have calculated ICT/ET and tissue myocardial performance index ([ICT+IRT]/ET)., Results: At univariate analysis, ET (RR: 0.80, 95% confidence interval [CI] 0.71-0.90, P < 0.001), ST (RR: 0.88, 95% CI 0.78-0.99, P < 0.05), FT (RR: 0.88, 95% CI 0.78-0.99, P < 0.05), ICT/ET (RR: 1.21, 95% CI 1.07-1.37, P < 0.01) were related to the occurrence of rehospitalization during follow-up. At multivariate Cox regression analysis, correlations remained significant for ET and ST (P < 0.05 and P < 0.01, respectively)., Conclusions: Time intervals assessed by TDI may be helpful in predicting the risk of rehospitalization in subjects with chronic HF., (© 2012, Wiley Periodicals, Inc.)

Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as coronary artery disease (CAD) and heart failure (HF). In these conditions, myocardial mitral annular systolic (S') and early diastolic (E') velocities have been shown to predict mortality or cardiovascular events. In heart failure non invasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/E') is a strong prognosticator, especially when E/E' is > or =15. Moreover, other parameters derived by TDI, as cardiac time intervals and Myocardial Performance Index, might play a role in the prognostic stratification in CAD and HF. Recently, a three-dimensional (3-D) TDI imaging modality, triplane TDI, has become available, and this allows calculation of 3-Dvolumes and LV ejection fraction. We present a brief update of TDI.