Hyperkinetic Arrhythmias Research Articles

P428 PRESCRIPTION APPROPRIATENESS AND EFFECTIVE CLINICAL IMPACT OF EXERCISE STRESS TEST IN ROUTINE DAILY PRACTICE

Abstract Rationale In the clinical setting, and particularly in the cardiovascular field, an exponential increase of non–invasive diagnostic tests has been observed. Between these, the exercise stress test represents a low–sensitivity and low–specificity diagnostic approach and its use has been less and less recommended in national and international guidelines. However, in the Italian clinical common practice it continues to be extensively prescribed both for chronic coronary syndrome (CCS) follow–up and for screening of coronary artery disease (CAD) in asymptomatic patients with multiple cardiovascular risk factors. Materials and Methods A retrospective cohort single–center study was conducted and 968 consecutives patients undergoing ECG stress test at our Department between October 2018 and March 2019 were included. Appropriateness of prescription and impact on the following diagnostic and therapeutic pathway has been analyzed. Results In this series, the main indication for exercise stress test was subclinical ischemia detection in CCS follow–up (312 pts, 32.3%). 181 tests (18.2%) were undertaken for CAD detection in patients symptomatic for chest pain and 171 (17.7%) for CAD detection in asymptomatic patients with multiple cardiovascular risk factors. At last, 97 tests (10%) were prescribed for arrhythmic burden evaluation and exercise response in patients with documented hyperkinetic arrhythmias. 590 tests (61%) were considered significative for reaching heart rate significance threshold (85% of target heart rate); between these 53 (9%) were positives for symptoms or ECG modifications. Among the positive tests, 25 patients (2.6%) went to the catheterization laboratory for coronary angiography: the indications for the exercise stress testing were chest pain for 14 of these patients while 7 undertook the examination for CCS follow–up. No asymptomatic patient presented for CAD screening undertook coronary angiography. At the end of the diagnostic pathway, 9 patients (0.9% of the complete cohort) received percutaneous or surgical revascularization. Conclusions Routinary and extensive use of exercise stress test can lead to dispersion of resources with many inappropriate examinations. Accurate clinical evaluation and appropriate prescription, especially regarding chest pain evaluation, are the foundations for a significative impact on clinical history of patients.

Pacemaker implantation in a COVID-19 patient. Balancing the patient's needs and the team's risk of exposure.

COVID-19 patients may have cardiovascular complications requiring invasive treatment. Pacemaker implantation procedure may be challenging because of the necessity of personal protective equipment use. We report pacemaker implantation in a 78-year-old man with severe bilateral COVID-19 interstitial pneumonia, a second degree 2:1 atrioventricular block, and concomitant aortic stenosis.

Acquired drug-induced long QTc: new insights coming from a retrospective study.

Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We do not know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus, we have retrospectively examined the clinical history of patients with diLQTc. The case record, concerning the period January 2008-December 2017, was collected from two hospitals. diLQTc was defined as drug-induced heart rate-corrected QT of ≥ 450ms or ≥ 470ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation). Seventy-three validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio, 0.998; 95% CI, 0.984 to 1.013; p = 0.8821). Likewise, a diQTc lasting longer than 500ms compared to diQTc comprised between 450 and 500ms was not associated with an increased risk of arrhythmic events. In our diLQTc patients, QTc duration did not predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking.

Caffeine intake reduces incident atrial fibrillation at a population level.

Background The general belief is that caffeine increases the risk of hyperkinetic arrhythmias, including atrial fibrillation. The aim of this study is to investigate the effect of chronic caffeine intake on incident atrial fibrillation in general population. Design and methods A population cohort of 1475 unselected men and women observed for 12 years and left free to intake food or beverages containing caffeine was studied. Subjects were stratified into tertiles of caffeine intake both in the whole cohort and after genotyping for the -163C > A polymorphism of the CYP1A2 gene, regulating caffeine metabolism. Results In the whole cohort, the 12-year incidence of atrial fibrillation was significantly lower in the third (2.2%) than in the first (10.2%) or second (5.7%) tertile of caffeine intake ( P < 0.001). The same trend was observed in all genotypes; the apparently steeper reduction of atrial fibrillation in slow caffeine metabolisers found at univariate analysis was proved wrong by multivariate Cox analysis. Age, chronic pulmonary disease, history of heart failure and of coronary artery disease, and systolic blood pressure - but not the genotype or the caffeine × CYP1A2 interaction term - were significant confounders of the association between incident atrial fibrillation and being in the third tertile of caffeine intake (hazard ratio 0.249, 95% confidence intervals 0.161-0.458, P < 0.01). Conclusions A higher caffeine intake (>165 mmol/day or > 320 mg/day) is associated with a lower incidence of atrial fibrillation in the 12-year epidemiological prospective setting based on the general population.

Malignant Ventricular Arrhythmias Resulting From Drug-Induced QTc Prolongation: A Retrospective Study.

BackgroundSeveral drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We don’t know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus we have retrospectively examined the clinical history of patients with diLQTc.MethodsThe case-record, concerning the period from January 2008 to December 2017, was collected from two hospitals. The diLQTc was defined as drug- induced heart rate-corrected QT of ≥ 450 ms or ≥ 470 ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation).ResultsA total of 73 validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio: 0.998; 95% CI: 0.984 to 1.013; P = 0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised between 450 and 500 ms was not associated with an increased risk of arrhythmic events.ConclusionsIn some probably genetically predisposed subjects, the occurrence of symptoms (dizziness, lipothymia, syncope ) and/or documented arrhythmic events (TdP), is related to intake of certain drugs (antiarrhythmics, antimicrobials such as quinolones and macrolides, etc.). Nevertheless, in our diLQTc patients, QTc duration didn’t predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking.

Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study

The relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassaemia major (TM). We evaluated a large retrospective historical cohort of TM to determine whether DM is associated with a higher risk of heart complications. We compared 86 TM patients affected by DM with 709 TM patients without DM consecutively included in the Myocardial Iron Overload in Thalassaemia database where clinical/instrumental data are recorded from birth to the first cardiovascular magnetic resonance (CMR) exam. All of the cardiac events considered were developed after the DM diagnosis. In DM patients versus non-DM patients we found a significantly higher frequency of cardiac complications (46.5% vs. 16.9%, P < 0.0001), heart failure (HF) (30.2% vs. 11.7%, P < 0.0001), hyperkinetic arrhythmias (18.6% vs. 5.5%, P < 0.0001) and myocardial fibrosis assessed by late gadolinium enhancement (29.9% vs. 18.4%, P = 0.008). TM patients with DM had a significantly higher risk of cardiac complications [odds ratio (OR) 2.84, P < 0.0001], HF (OR 2.32, P = 0.003), hyperkinetic arrhythmias (OR 2.21, P = 0.023) and myocardial fibrosis (OR 1.91, P = 0.021), also adjusting for the absence of myocardial iron overload assessed by T2* CMR and for the covariates (age and/or endocrine co-morbidity). In conclusion, DM significantly increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis in TM patients.

Synergic Effect of Fludrocortisone and Disopyramide in an Elderly Patient with Orthostatic Syncope

Orthostatic hypotension (OH) is a debilitating condition very common in the elderly that may leads to syncope. There is no single drug able to limit the fall in blood pressure in patients affected by OH when standing. In addition, the presence of hyperkinetic arrhythmias may worsen the fall in orthostatic blood pressure especially in elderly patients affected by OH. Unfortunately most of antiarrhythmic therapies lead to a decrease in blood pressure contrasting the effect of OH treatment. By contrast, disopyramide seems to have an anticholinergic effect that could play an important role in limiting the fall in blood pressure in participants with hyperkinetic arrhythmias and OH. We report a case of successful combination therapy of fludrocortisone, disopyramide and nonpharmacologic treatment in an elderly participant affected by neurogenic orthostatic OH and hyperkinetic arrhythmias with a poor quality of life and frequent syncope episodes.

Diabetes mellitus and cardiac complications in thalassemia major patients

Background The relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassemia major (TM). The aim of this crosssectional study was to evaluate in a large historical cohort of TM in the cardiovascular magnetic resonance (CMR) era if DM was associated with an higher prevalence and risk of heart complications, also regardless to the presence of myocardial iron overload (MIO). Methods We compared 86 TM patients affected by DM with 709 TM patients without DM enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network at their first CMR. The MIOT network involves 68 thalassemia centers and 8 CMR sites where the exams are performed using standardized and validated procedures and all centers are linked to a web-based database to collect and share patients’ history, clinical and diagnostic data. Cardiac iron was evaluated by T2* multiecho multislice technique. Biventricular function parameters were quantitatively evaluated by cine images. Myocardial fibrosis was evaluated by late gadolinium enhacement CMR technique. Heart failure (HF) was diagnosed by CMR in presence of a left ventricular (LV) and/or right ventricular (RV) ejection fraction (EF) lower than 4 standard deviations from the mean value normalized by sex and age. Moreover HF was identified by patients’ history, diagnosed by clinicians based on symptoms, signs and echocardiographic findings. All considered cardiac events were developed after the DM diagnosis. Results In DM patients versus no-DM patients we found a significantly higher prevalence of cardiac complications (HF, arrhythmias and pulmonary hypertension) (46.5% vs 16.9%, P<0.0001), HF (30.2% vs 11.7%, P<0.0001), hyperkinetic arrhythmias ECG documented and requiring medications (18.6% vs 5.5%, P<0.0001), and myocardial fibrosis (29.9% vs 18.4%, P=0.008). To evaluate the impact of the DM on cardiac complications also in relationship to MIO, we always adjusted the risk of cardiac findings for the absence of MIO (all segments with T2*≥20 ms). Patients with DM had a significant higher risk of cardiac complications (OR 2.84, P<0.0001), HF (OR 2.32, P=0.003), hyperkinetic arrhythmias (OR 2.21, P=0.023) and myocardial fibrosis (OR 1.91, P=0.021). Conclusions DM increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis irrespective of MIO. Funding “No-profit” support by industrial sponsorships (Chiesi, Apotex and GE Healtcare) and “Ministero della Salute, fondi ex art. 12 D.Lgs. 502/92 es .m.i., ricerca sanitaria finalizzata anno 2006” e “Fondazione L. Giambrone”.

Diabetes Mellitus and Cardiac Complications in Thalassemia Major Patients

Abstract 2150 Introduction.In thalassemia major (TM) patients myocardial iron overload and chronic anemia are the recognized leading causes of cardiomyopathy, but a role can also be played by other factors such as endocrine abnormalities. The aim of this retrospective study was to evaluate if diabetes mellitus (DM) was associated with an higher prevalence and risk of cardiac dysfunction and of heart complications, regardless to the presence of myocardial iron overload. Methods.From a cohort of 957 TM patients who underwent MRI within the MIOT network (Myocardial Iron Overload in Thalassemia), among the patients (N = 358) with no cardiac iron (all cardiac segments with a T2* ≥ 20 ms) we identified 29 patients with DM and 329 patients without DM. The normal values of ejection fraction (EF) normalized by sex and age, obtained in a cohort of 142 TM patients without cardiac disease and iron overload, were used to define left ventricular (LV) and right ventricular (RV) heart dysfunction (EF < mean – 2 standard deviation). Heart failure (HF) was diagnosed by Magnetic Resonance Imaging (MRI) in presence of a LV and/or RV EF lower than 4 standard deviations from the normalized mean value and by a positive history (clinical symptoms, confirmation by physical examination and treatment). Myocardial fibrosis was evaluated by delayed enhancement MRI technique. Results.The prevalence of overall heart dysfunction (LV, RV or both) was higher in patients with DM (44.8%) versus patients without DM (28.3%), with a P-value very close to the statistically significance (P=0.061). In more details, patients with DM presented significantly more biventricular dysfunction (20.7% vs 7.6%, P=0.016). The prevalence of myocardial fibrosis was significantly higher in the DM patients vs the no DM patients (37.5% vs 19.2 %; P=0.033). Cardiac complications occurred with a significantly higher frequency in patients with DM (55.2% vs 15.5%, P<0.0001). Taking into account each cardiac complication separately, a significant difference between the groups was found in the occurrence of heart failure (27.6% vs 9.4%, P<0.003) and hyperkinetic arrhythmias (34.5% vs 5.2%,P<0.0001), both supraventricular (27.6% vs 4%, P<0.0001) and ventricular (6.9% vs 0.6%, P=0.034).Table 1 shows odds ratios (OR) estimating the relationship between diabetes and cardiac involvement. Among cardiac dysfunctions, only the biventricular forms were significantly positively associated with the diabetes. However, the correction for age caused the loss of the significance. The association between DM and myocardial fibrosis became not significant after the correction for age and endocrine co-morbidity. Patients with DM were significantly more likely to have cardiac complications and the results were not affected by the adjustment for age and/or endocrine co-morbidity. Considering separately each cardiac complication, a significant association was found for HF and hyperkinetic arrhythmias. The association between DM and HF resulted not significant after the correction for age. For the hyperkinetic arrhythmias, the OR remained significant after the correction for age and/or endocrine co-morbidity. Conclusion.In TM patients without myocardial iron DM was significantly associated with the presence of cardiac complications globally considered and hyperkinetic arrhythmias.Table 1Logistic regression models for cardiac involvement in TM patients without myocardial iron overload.No correctionCorrection for ageCorrection for endocrine co-morbidityCorrection for age and endocrine co-morbidityORP-valueORP-valueORP-valueORP-valueOverall dysfunction2.00.0661.40.4062.10.0661.50.366Biventricular dysfunction3.20.0221.70.3203.10.0261.80.313Fibrosis2.50.0382.30.0742.30.0822.20.110Cardiac complications6.7<0.00013.60.0045.5<0.00013.30.007Heart failure3.70.0042.20.1252.90.0192.00.170Hyperkinetic arrhythmias9.7<0.00013.70.0087.3<0.00013.50.015Pulmonary hypertension00.99800.99800.99800.998 Disclosures:No relevant conflicts of interest to declare.

Cardiovascular Properties of the Non-Volatile Total Residue from the Essential Oil of Citrus bergamia

In the context of research towards defining the spectrum of biological activities of Citrus bergamia Risso (Bergamot, Rutaceae), cardiovascular activity of the non-volatile total residue (NVTR) from the essential oil of this plant was investigated in a variety of experimental in vivo and in vitro models and have been compared with verapamil. In the anaesthetized Guinea-pigs, the NVTR showed a protective effect against pitressin-induced coronary spasm, arrhythmias and pressor response; a protective and suppressive effects on ouabain induced ventricular arrhythmias. On rat isolated heart, the NVTR exerts a coronary-dilator action and is able to reduce the hyperkinetic ventricular arrhythmias caused by post-ischaemic reperfusion. These results demonstrate that the non-volatile residue possesses significant cardiovascular properties with a profile similar to that of the verapamil.

Does captopril treatment before thrombolysis in acute myocardial infarction attenuate reperfusion damage? Short-term and long-term effects

Several experimental studies carried out on animals and on isolated heart preparations show that captopril can reduce post-ischemic reperfusion injury. Our study was aimed at investigating the effects of captopril before thrombolysis in acute myocardial infarction (AMI) and included 259 patients, hospitalized within 4 h of the onset of symptoms. Patients were randomly subdivided into two groups: the first group (131 patients, Group A, pretreatment) received 6.25 mg captopril orally about 15 min before i.v. administration of urokinase (2 million), the second group (128 patients, Group B, late-treatment), received captopril about 3 days after thrombolytic treatment. Captopril doses were later increased in both groups according to blood pressure. All patients were subdivided according to the localization of infarction. Anterior AMI was shown by 166 patients (84 from Group A and 82 from Group B); 93 patients showed inferior AMI (47 from Group A and 46 from Group B). Ventricular hyperkinetic arrhythmias (VHAs) due to reperfusion were evaluated during the first 2 h. VHAs occurred in 11.9% of patients with anterior AMI in Group A vs. 37.8% in Group B ( P < 0.001). CK peak normalization time in the group with anterior AMI was achieved after 58 ± 2 h in Group A vs. 71 ± 2 h in Group B ( P < 0.001). CK peak was 1719 ± 152 in Group A vs. 2184 ± 164 U/1 in Group B, ( P < 0.039). Late arrhythmias, higher than Lown's Class 2 were found to occur in 15.4% of patients with anterior AMI of Group A vs. 31.7% in Group B ( P < 0.022), at predischarge Holter test. One-hundred fifty-one patients underwent hemodynamic testing about 3 weeks from AMI. Seventy-seven patients belonged to Group A, 51 with anterior AMI (60%) and 26 with inferior AMI (55.3%), and 74 to Group B, 47 anterior AMIs (57%) and 27 inferior AMIs (58.6%). Ejection fraction and end-systolic volume did not show a statistically significant difference between the two groups. Follow-up (mean, 30.5 ± 2 months) was carried out on 259 patients. There were 131 patients in Group A (84 with anterior AMI and 47 inferior AMI) and 128 in the Group B (82 anterior AMI and 46 inferior AMI). Mortality of patients with anterior AMI was 5.95% in Group A versus 17.07% in Group B ( P < 0.045).

Lethal hyperkinetic ventricular arrhythmias and echocardiographic findings in patients with arrhythmogenic right ventricular disease

Lethal hyperkinetic ventricular arrhythmias and echocardiographic findings in patients with arrhythmogenic right ventricular disease