Novel findings of an old algorithm: PVC response "Atrial Pace'' initiates atrial arrhythmias in Abbott ICD and CRT-D devices.

BACKGROUND: Many algorithms have been developed to ensure the safety and accuracy of cardiac implantable electric devices (CIED). A specific algorithm designed to prevent pacemaker induced tachycardia (PMT) after a premature ventricular complex (PVC response) is available in all Abbott (former St. Jude Medical) CIED. However, a few case reports suggest that this algorithm may be proarrhythmic when programmed to Atrial Pace (A-Pace on PVC). METHODS: We analyzed the data of all (n = 333) Abbot implantable cardioverter defibrillator (ICD) and cardiac resynchronization defibrillator (CRT-D) devices followed remote using the Merlin.net Patient Care Network in our institute in 2020. Status of the PVC response algorithm A-Pace on PVC or Off was collected, and all atrial mode switch (AMS) episodes longer than 30 s were thoroughly evaluated. Data on clinical characteristics of the patients was collect from the electronic patient records. RESULTS: A total of 173 patients had A-Pace on PVC and twenty-five of them (14%) had at least one atrial high rate episode (AHRE) >30 s (AHRE) triggered by the action of this algorithm. The median PVC count was higher in patients who had algorithm triggered AHRE than in those with no algorithm-triggered AHRE (1.7% [IQR 0-3.2] vs. 0% [IQR 0-1.1], p < .0001). The major clinical characteristics were comparable in the two groups. CONCLUSION: The A-Pace on PVC setting was frequently used in our patients. Our study shows that a considerable number of patients had at least one AHRE triggered by the algorithm. The use of this algorithm should be carefully reconsidered.

Adjuvant radiotherapy-induced cardiac changes among patients with early breast cancer: a three-year follow-up study.

Background: In this study, we evaluate the evolution of cardiac changes during a three-year follow-up after adjuvant breast radiotherapy (RT). Methods: Sixty patients with left-sided and 20 patients with right-sided early stage breast cancer without chemotherapy were included in this prospective study. Echocardiography and cardiac biomarkers were evaluated before, immediately after and 3 years after RT. Radiation doses to cardiac structures were calculated. Results: In echocardiography, left ventricle (LV) systolic measurements had impaired at 3 years compared to baseline: the mean global longitudinal strain (GLS) worsened from -18 ± 3 to -17 ± 3 (p = .015), LV ejection fraction from 62 ± 5% to 60 ± 4% (p = .003) and the stroke volume from 73 ± 16 mL to 69 ± 15 mL (p = .015). LV diastolic function was also negatively affected: the isovolumetric relaxation time was prolonged (p = .006) and the first peak of diastole decreased (p = .022). Likewise, left atrial (LA) measurements impaired. These changes in echocardiography were more prominent in left-sided than in right-sided patients. The concurrent aromatase inhibitor (AI) use was associated with GLS impairment. In all patients, the N-terminal pro-brain natriuretic peptide (proBNP) values were median (interquartile range) 74 (41-125) ng/L at baseline, 75 (41-125) ng/L at the end of RT and 96 (56-162) ng/L at 3 years (p < .001 from baseline to 3 years). However, proBNP did not increase in right-sided patients. Conclusion: During the 3-year follow-up after RT, negative subclinical changes in cardiac biomarkers and in LV systolic and diastolic function were observed. The measured changes were more pronounced in left-sided patients. In addition, AI use was associated with impaired cardiac systolic function.

Poor Quality of Warfarin Treatment Increases the Risk of All Types of Intracranial Hemorrhage in Atrial Fibrillation.

BACKGROUND: Intracranial hemorrhage (ICH) is a devastating complication of oral anticoagulation. The aim of this study was to describe the spectrum of ICH and to evaluate the association of warfarin control with the risk of ICH in a nationwide cohort of unselected atrial fibrillation (AF) patients. Methods and Results: The FinWAF is a retrospective registry-linkage study. Data were collected from several nationwide Finnish health-care registers and laboratory databases. The primary outcome was any ICH (traumatic or non-traumatic). The quality of warfarin therapy was assessed continuously by calculating the time in therapeutic range in a 60-day window (TTR60). Adjusted Cox proportional hazard models were used. A total of 53,953 patients were included (53% men; mean age, 73 years; mean follow-up, 2.94 years; mean TTR, 63%). In 129,684 patient-years, 1,196 patients had ICH (non-traumatic, 53.5%; traumatic, 43.6%; traumatic subdural, 38.6%); crude annual rate, 0.92%; 95% CI: 0.87-0.98). A lower TTR60 was significantly associated with higher risk of ICH (TTR60 ≤40% vs. TTR60 >80%; adjusted hazard ratio, 2.16; 95% CI: 1.83-2.54). Other variables independently associated with ICH included age >65 years, previous stroke, male sex, low hemoglobin, thrombocytopenia, elevated alanine aminotransferase, and previous bleeding other than ICH. CONCLUSIONS: Poor control of warfarin treatment was associated with elevated risk of ICH. Approximately half of the ICH were traumatic, mainly subdural.

Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation: The CAPTAF Randomized Clinical Trial.

Importance: Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication. Objective: To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation. Design, Setting, and Participants: Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or ß-blocker, with 4-year follow-up. Study dates were July 2008-September 2017. Major exclusions were ejection fraction <35%, left atrial diameter >60 mm, ventricular pacing dependency, and previous ablation. Interventions: Pulmonary vein isolation ablation (n = 79) or previously untested antiarrhythmic drugs (n = 76). Main Outcomes and Measures: Primary outcome was the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis. Results: Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P = .003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8% [95% CI, -12.9% to -0.7%]; P = .03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group. Conclusions and Relevance: Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life. Trial Registration: clinicaltrialsregister.eu Identifier: 2008-001384-11.

Higher burden of supraventricular ectopic complexes early after catheter ablation for atrial fibrillation is associated with increased risk of recurrent atrial fibrillation.

Aims: Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results: A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and ≥ 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF ≥ 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (≥ 783 SVEC: HR 4.6 [1.9-11.5], P < 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence < 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC ≥ 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion: Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.

Associations between ECG changes and echocardiographic findings in patients with acute non-ST elevation myocardial infarction.

BACKGROUND: ST segment depression (STD) and T wave inversion (TWI) are typical electrocardiographic (ECG) findings in non-ST elevation myocardial infarction (NSTEMI). In ST elevation myocardial infarction, ST changes represent transmural ischemia. The pathophysiological mechanisms of the ECG changes in NSTEMI are unclear. PURPOSE: We studied the associations between ECG and the echocardiographic findings in NSTEMI patients. METHODS: Twenty patients with acute NSTEMI were recruited during their hospital stay. A comprehensive echocardiography study was performed. The findings were compared with blinded ECG analyses. RESULTS: Nine (45%) patients had STD, and 16 (85%) patients had TWI. In multivariable analysis, STD was independently associated with a lower global early diastolic strain rate (ß=-5.061, p=0.033). TWI was independently associated with lower circumferential strain (ß=0.132, p=0.032). CONCLUSIONS: The typical ECG changes in NSTEMI patients were associated with subtle echocardiographic changes. STD was related to changes in diastolic function, and TWI was associated with systolic deterioration.

Contemporary management of patients undergoing atrial fibrillation ablation: in-hospital and 1-year follow-up findings from the ESC-EHRA atrial fibrillation ablation long-term registry.

AIMS: The ESC-EHRA Atrial Fibrillation Ablation Long-Term registry is a prospective, multinational study that aims at providing an accurate picture of contemporary real-world ablation for atrial fibrillation (AFib) and its outcome. METHODS AND RESULTS: A total of 104 centres in 27 European countries participated and were asked to enrol 20-50 consecutive patients scheduled for first and re-do AFib ablation. Pre-procedural, procedural and 1-year follow-up data were captured on a web-based electronic case record form. Overall, 3630 patients were included, of which 3593 underwent an AFib ablation (98.9%). Median age was 59 years and 32.4% patients had lone atrial fibrillation. Pulmonary vein isolation was attempted in 98.8% of patients and achieved in 95-97%. AFib-related symptoms were present in 97%. In-hospital complications occurred in 7.8% and one patient died due to an atrioesophageal fistula. One-year follow-up was performed in 3180 (88.6%) at a median of 12.4 months (11.9-13.4) after ablation: 52.8% by clinical visit, 44.2% by telephone contact and 3.0% by contact with the general practitioner. At 12-months, the success rate with or without antiarrhythmic drugs (AADs) was 73.6%. A significant portion (46%) was still on AADs. Late complications included 14 additional deaths (4 cardiac, 4 vascular, 6 other causes) and 333 (10.7%) other complications. CONCLUSION: AFib ablation in clinical practice is mostly performed in symptomatic, relatively young and otherwise healthy patients. Overall success rate is satisfactory, but complication rate remains considerable and a significant portion of patients remain on AADs. Monitoring after ablation shows wide variations. Antithrombotic treatment after ablation shows insufficient guideline-adherence.

Quality of warfarin therapy and risk of stroke, bleeding, and mortality among patients with atrial fibrillation: results from the nationwide FinWAF Registry.

PURPOSE: The most important management strategy in atrial fibrillation (AF) patients is preventing stroke with oral anticoagulants. Warfarin is still used as a first-line anticoagulant, although non-vitamin K antagonist oral anticoagulants are currently recommended to manage AF. Using a large, unselected national sample of AF patients, we evaluated the relationships between quality of warfarin therapy and the risks of thromboembolism, bleeding complications, and mortality. METHODS: The nationwide FinWAF study included 54 568 AF patients taking warfarin. Time in the therapeutic range (TTR) was calculated on a continuous basis using the Rosendaal method and international normalized ratio values over the previous 60 days. Adjusted Cox proportional hazard models were prepared for different TTR levels and major clinical end points. RESULTS: The mean age of patients was 73.1 years (standard deviation 10.8), and 47% were female. The mean follow-up time was 3.2 ± 1.6 years (median 3.4). In the TTR groups of ≤40%, 60-70%, 70-80%, and >80%, the annual risk of stroke was 9.3%, 4.7%, 4.6%, and 3.1%; bleeding events 7.5%, 4.5%, 4.3%, and 2.6%; and overall mortality 20.9%, 8.5%, 6.4%, and 3.1%, respectively. All differences among the TTR groups were highly significant (p < 0.001). CONCLUSIONS: The quality of warfarin treatment was strongly associated with the risk of stroke and the prognosis of AF patients. Patient outcomes continued to improve with increasing TTR values up to a TTR ≥80%; therefore, the target for the TTR should exceed 80% instead of the traditional range of at least 60-70%. Copyright © 2017 John Wiley & Sons, Ltd.

Detection of early radiotherapy-induced changes in intrinsic myocardial contractility by ultrasound tissue characterization in patients with early-stage breast cancer.

BACKGROUND: Increased cardiovascular morbidity and mortality are major late complications after radiotherapy (RT) in the thoracic region. Ultrasound tissue characterization (UTC) is a noninvasive method for the identification of myocardial changes. The aim of this prospective clinical trial was to assess whether the analysis of cyclic variation of integrated backscatter (CVIBS) can detect early RT-induced myocardial alterations. METHODS: Seventy-three eligible patients with early-stage breast cancer were evaluated before and immediately after adjuvant RT. Twenty and 53 patients had right-sided and left-sided breast cancer, respectively. None of the patients received chemotherapy. Comprehensive echocardiographic examination included three-dimensional (3D) measurements and UTC analysis of the left ventricular (LV) septum and posterior wall. RESULTS: RT reduced CVIBS in a dose-dependent manner. The mean heart radiation dose over two gray (Gy) reduced the septal CVIBS from 12.0±3.4 to 9.6±2.5 dB (P<.001) and the posterior wall CVIBS from 12.8±2.7 to 11.3±2.4 dB (P=.007). The CVIBS remained unchanged when the mean heart RT dose was below 2 Gy. Multivariate analysis showed an independent association with a change in septal CVIBS and the use of aromatase inhibitor (ß=2.986, P=.001) and body mass index (ß=-0.241, P=.014). The posterior values were worse with higher mean lung dose (ß=-.485, P=.018) and with nonsmoking status (ß=-2.411, P=.009). Echocardiography parameters showed increased myocardial mass but conventional measurements of the LV systolic function remained unchanged. CONCLUSIONS: Cyclic variation of integrated backscatter analysis seems to be a sensitive method to detect early RT-induced myocardial changes. Hence, it may be useful in screening of patients needing closer follow-up.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.

BACKGROUND: There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS: We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS: There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS: In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).

The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from a MANTRA-PAF substudy.

AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients. CONCLUSION: Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).

[Update on current care guideline: atrial fibrillation]. / Eteisvärinä.

The prevalence and incidence of atrial fibrillation (AF) are increasing rapidly. Key recommendations in management of AF include prompt administration of oral anticoagulation to all patients with elevated risk of thromboembolic complications, proper use of antiarrhythmic drugs and invasive therapies in highly symptomatic patients and adequate rate control in patients with permanent AF. The selection between warfarin and the novel oral anticoagulants (apixaban, dabigatran, rivaroxaban) is based on careful evaluation of the benefits and disadvantages of the drugs in a given patient.

Repolarization abnormalities in patients with subarachnoid and intracerebral hemorrhage: predisposing factors and association with outcome.

BACKGROUND: Electrocardiographic (ECG) abnormalities are frequent in patients with intracranial insult. In this study, we evaluated the factors predisposing to the repolarization abnormalities, i.e., prolonged corrected QT (QTc) interval, ischemic-like ECG changes and morphologic end-repolarization abnormalities, and examined the prognostic value of these abnormalities in patients with subarachnoid and intracerebral hemorrhages requiring intensive care. METHODS: This was a prospective, observational clinical study in a university-level intensive care unit. Clinical characteristics, the level of consciousness, and findings in primary head computed tomography were recorded on admission. The study period was divided into three 2-day sections. In each section, a 12-lead ECG, transthoracic echocardiography, the results of standard blood electrolytes and cardiac troponin I, as well as the rate of vasoactive and sedative drug infusions were recorded. Repolarization abnormalities such as prolongation of the QTc interval (millisecond), ischemic-like ECG changes, and morphologic end-repolarization abnormalities (present/absent) were evaluated and analyzed. The 1-year functional outcome was determined using the Glasgow Outcome Score. RESULTS: During the 2-year study period, 108 patients were included in the study. Different repolarization abnormalities were frequent in both types of hemorrhage. Prolongation of the QTc interval was predisposed by female gender (ß, 24.5; P = 0.010) and the use of propofol (ß, 30.5; P = 0.001). The predisposing factor for ischemic-like ECG changes were male gender (odds ratio [OR], 5.9; P = 0.003) and for morphological end-repolarization abnormalities aneurysmatic bleeding (OR, 13.0; P = 0.002). Ischemic-like ECG changes were common, in 87/108 patients during the study period, and were associated with a poorer 1-year functional outcome (OR, 4.7; lower 95% confidence interval, 1.5; P = 0.010). CONCLUSIONS: Each repolarization abnormality has characteristic predisposing factors. Ischemic-like ECG changes are common and are associated with a poorer 1-year functional outcome.

Detection of concurrent atrial ischemia with continuous monitoring of dynamic PR-segment changes in patients with acute myocardial infarction.

Despite its potential prognostic value concurrent atrial ischemia is often overlooked in patients with acute myocardial infarction (AMI). There is no study concerning the relationship between atrial coronary circulation and dynamic PR-segment changes in patients with AMI. We evaluated dynamic PR-segment changes in 37 patients with AMI. The flow in the principal atrial coronary branches was diminished in 14 (38%) patients. Dynamic changes in the PR-segment level [median 47 (inter quartile range 19-55) µV vs. 23 (18-30) µV, P=0.005] and PR-segment area [3.15 (1.75-3.69) nVs vs. 1.62 (1.18-2.04) nVs, P=0.005] were significantly greater in patients with compromised than in those with normal flow in the atrial coronary branches. Our findings support the concept that atrial ischemia produces similar changes in the PR-segment as ventricular ischemia in the ST-segment. Given the possible deleterious consequences of atrial ischemia these data may have important clinical implications in evaluation of patient with AMI.

Transseptal snaring technique as a bailout from valvuloplasty balloon entrapment within a self-expanding valve: a case report.

Background: Transcatheter aortic valve replacement (TAVR) has become the dominant treatment strategy for severe aortic stenosis in patients with high and intermediate surgical risk. Although complications are significant cause of increasing mortality after TAVR and bailout techniques have been well established, we still encounter a rare complication without widely accepted bailout option. We present a rare complication of valvuloplasty balloon entrapment to a self-expanding valve strut with successful bailout. Case summary: A 71-year-old man complaining of dyspnoea underwent valve-in-valve TAVR for failed surgical aortic valve. However, he developed acute decompensated heart failure due to high residual aortic gradient (peak aortic velocity of 4.0 m/s and mean aortic gradient of 37 mmHg) on the 3rd day after TAVR. Computed tomography demonstrated underexpansion of transcatheter heart valve (THV) within the surgical valve. Therefore, urgent balloon valvuloplasty was performed. The balloon entrapment in the THV stent frame happened during the procedure. Percutaneous removal through transseptal approach using snaring technique was successfully performed. Discussion: Balloon entrapment within a THV is a rare complication and potentially requires urgent surgical removal. To our knowledge, this is the first report utilizing the snaring technique through transseptal approach for balloon entrapment within a THV. Through the current report, we highlight the utility and effectiveness of the transseptal snaring technique with using a steerable transseptal sheath. Moreover, this case shows the importance of the multiprofessional approach to resolve unexpected complications.

Associations of anaemia with bleeding and thrombotic complications in patients with atrial fibrillation treated with warfarin: a registry-based nested case-control study.

OBJECTIVES: We studied association of laboratory testing beyond the international normalised ratio (INR) with bleeding and stroke/transient ischaemic attack (TIA) outcomes in patients with atrial fibrillation treated with warfarin. DESIGN: This was a retrospective nested case-control study from the Finnish Warfarin in Atrial Fibrillation (FinWAF) registry (n=54 568), reporting the management and outcome in warfarin-anticoagulated patients. Associations of blood count test frequency and results were assessed together with risk of bleeding or stroke/TIA during 5-year follow-up. SETTING: National FinWAF registry, with data from all six hospital districts. Follow-up period for complications was 1 January 2007-31 December 2011. PARTICIPANTS: A total of 54 568 warfarin-anticoagulated patients. RESULTS: The number of patients with bleeding was 4681 (9%) and stroke/TIA episodes, 4692 (9%). In patients with bleeds, lower haemoglobin (within 3 months) preceded the event compared with the controls (median 126 vs 135 g/L; IQR 111-141 g/L vs 123-147 g/L, p<0.001), while patients with stroke/TIA had only modestly lower INR (median 2.2 vs 2.3; 1.8-2.6 vs 2.1-2.7, p<0.001). When the last measured haemoglobin was below the reference value (130 g/L for men, 120 g/L for women), the OR for a bleeding complication was 2.9 and stroke/TIA, 1.5. If the haemoglobin level was below 100 g/L, the complication risk increased further by 10-fold. If haemoglobin values were repeatedly (more than five times) low during the preceding 3 months, future OR was for bleeds 2.3 and for stroke/TIA 2.4. CONCLUSIONS: The deeper the anaemia, the higher the risk of bleeding and stroke/TIA. However, INR remained mainly at its target and only occasionally deviated, failing to detect the complication risk. Repeated low haemoglobin results, compatible with persistent anaemia, refer to suboptimal management and increased the complication risk in anticoagulated patients.

Radiotherapy-induced diffuse myocardial fibrosis in early-stage breast cancer patients - multimodality imaging study with six-year follow-up.

BACKGROUND: Breast radiotherapy (RT) induces diffuse myocardial changes, which may increase the incidence of heart failure with preserved ejection fraction. This study aimed to evaluate the early signs of diffuse fibrosis after RT and their evolution during a six-year follow-up. METHODS: Thirty patients with early-stage left-sided breast cancer were studied with echocardiography and electrocardiography (ECG) at baseline, after RT, and at three-year and six-year follow-up visits. Echocardiography analysis included an off-line analysis of integrated backscatter (IBS). ECG was analysed for fragmented QRS (fQRS). In addition, cardiac magnetic resonance (CMR) imaging was performed at the six-year control. The left ventricle 16-segment model was used in cardiac imaging, and respective local radiation doses were analysed. RESULTS: Regional myocardial reflectivity in inferoseptal segments increased by 2.02 (4.53) dB (p = 0.026) and the percentage of leads with fQRS increased from 9.2 to 16.4% (p = 0.002) during the follow-up. In CMR imaging, abnormal extracellular volume (ECV) and T1 mapping values were found with anteroseptal and apical localization in a median of 3.5 (1.00-5.75) and 3 (1.25-4.00) segments, respectively. A higher left ventricle radiation dose was associated with an increased likelihood of having changes simultaneously in CMR and echocardiography (OR 1.26, 95% Cl. 1.00-1.59, p = 0.047). CONCLUSIONS: After radiotherapy, progressive changes in markers of diffuse myocardial fibrosis were observed in a multimodal manner in ECG and echocardiography. Changes in echocardiography and abnormal values in CMR were localized in the septal and apical regions, and multiple changes were associated with higher radiation doses.

Dynamic Integrated Backscatter Detects Radiotherapy-induced Cardiac Changes Better than Strain Analysis - A Prospective Three-year Study.

BACKGROUND/AIM: Radiotherapy (RT) related myocardial changes were analyzed by deformation imaging echocardiography in this study. PATIENTS AND METHODS: Ninety-nine breast cancer patients were studied at baseline, after chemotherapy, after RT, and three years after RT (3Y). Eighty patients received RT only, and twenty patients had right-sided breast cancer. Echocardiography included cyclic variation of the integrated backscatter in the septum (sCV) and posterior wall (pCV), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF). RESULTS: In patients with left-sided breast cancer, sCV declined from 11.3±3.3 dB at baseline to 10.3±2.9 dB after RT (p=0.001). No changes were observed after chemotherapy (p=0.211) or in patients with right-sided breast cancer after RT (p=0.977). No other parameters declined after RT. The decline in sCV was independently associated with the left anterior descending coronary artery radiation dose (ß=-0.290, p=0.020). CONCLUSION: In contrast to other parameters, sCV correlated with heart radiation dose.

A Higher Mean Heart Radiation Dose Induces Higher Frequency of Multiple Cardiac Changes.

BACKGROUND/AIM: Radiotherapy (RT) induces late changes in all cardiac structures. Most studies of early changes focus on individual parameters. PATIENTS AND METHODS: Data from eighty early-stage breast cancer patients at baseline, post-RT and three-year follow-up visit were assessed prospectively. Changes in ten cardiac parameters were collected including electrocardiogram (ECG), echocardiography, and biomarkers. A percentage of abnormal changes was calculated. RESULTS: The mean heart radiation dose (Dmean) was independently associated with the increased incidence of changes post-RT (ß=0.403, p<0.001) and at the three-year follow-up (ß=0.353, p=0.001). Each 1-Gray increase in Dmean increased the cardiac changes by 3.7% (95%CI=1.9-5.6%) after RT and 3.1% (95%CI=1.3, 4.9%) at the three-year follow-up. CONCLUSION: A higher cardiac radiation dose was independently associated with a higher incidence of changes in cardiac parameters. Multiparameter changes imply that the early phase after RT is already characterized by several overlapping cardiac changes.