Israel Medical Association Journal

Background: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events.

Objectives: To investigate whether CHA₂DS₂-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke.

Methods: We analyzed data of 2628 patients, aged 40–65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA₂DS₂-VASc scores categorized by subgroups (score 2–3, 4–5, or 6–7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months.

Results: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40–60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2–3, 4–5, and 6–7, respectively. In a multivariate cox regression model, compared to patients with score 2–3 (reference group), those with score 4–5 and 6–7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41–2.14) and 2.87 (95%CI 2.10–3.93), respectively. The discriminative capacity of CHA₂DS₂-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60–0.66), although better for myocardial infarction 0.69 (95% CI 0.61–0.77).

Conclusions: CHA₂DS₂-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

Background: Direct oral anticoagulants (DOACs) are the treatment of choice for patients with non-valvular atrial fibrillation; however, bleeding risk remains significant. We reported a single-center experience with 11 patients who presented with hemorrhagic cardiac tamponade while treated with DOACs.

Objectives: To evaluate the characteristics and clinical outcomes of patients under DOACs with cardiac tamponade.

Methods: We retrospectively identified 11 patients treated with DOACs admitted with pericardial tamponade in our cardiology unit during 2018–2021.

Results: The mean age was 84 ± 4 years; 7 males. Atrial fibrillation was the indication for anticoagulation in all cases. DOACs included apixaban (8 patients), dabigatran (2 patients), and rivaroxaban (1 patient). Urgent pericardiocentesis via a subxiphoid approach under echocardiography guidance was successfully performed in 10 patients. One patient was treated with urgent surgical drainage with a pericardial window. Reversal of anticoagulation using prothrombin complex concentrate and idarucizumab was given before the procedure to 6 patients treated with apixaban and one patient treated with dabigatran. One patient, initially treated with urgent pericardiocentesis, underwent pericardial window surgery due to re-accumulation of blood in the pericardium. The pericardial fluid analysis demonstrated hemopericardium. Cytology tests were negative for malignant cells in all cases. Discharge diagnoses regarding the cause of hemopericardium included pericarditis (3 patients) and idiopathic (8 patients). Medical therapy included non-steroidal anti-inflammatory drugs (1 patient), colchicine (3 patients), and steroids (3 patients). No patient died during hospitalization.

Conclusions: Hemorrhagic cardiac tamponade is a rare complication of DOACs. We found good short-term prognosis following pericardiocentesis.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Previous studies showed that rhythm and rate control strategies are associated with similar rates of mortality and serious morbidity. Beta blockers (BB) and calcium channel blockers (CCB) are commonly used and the selection between these two medications depends on personal preference.

Objectives: To compare real-time capability of BB and CCB for the treatment of rapid AF and to estimate their efficacy in reducing hospitalization duration.

Methods: We conducted a retrospective cohort study of 306 patients hospitalized at Soroka Hospital during a 5-year period with new onset AF who were treated by a rate control strategy.

Results: A significant difference between the two groups regarding the time (in hours) until reaching a target heart rate below 100 beats/min was observed. BB were found to decrease the heart rate after 5 hours (range 4–14) vs. 8 hours (range 4–18) for CCB (P = 0.009). Patients diagnosed with new-onset AF exhibited shorter duration of hospitalization after therapy with BB compared to CCB (median 72 vs. 96 hours, P = 0.012) in the subgroup of patients discharged with persistent AF. There was no significant difference between CCB and BB regarding the duration of hospitalization (P = 0.4) in the total patient population.

Conclusions: BB therapy is more potent for rapid reduction of the heart rate compared to CCB and demonstrated better efficiency in shortening the duration of hospitalization in a subgroup of patients. This finding should be reevaluated in subsequent research.

Background: The CHA₂DS₂-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF).

Objectives: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA₂DS₂-VASc score in SR.

Methods: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA.

Results: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA₂DS₂-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA₂DS₂-VASc group (45, interquartile ratio [IQR] 36–49) vs. 37 (IQR 28–46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7–9.3) vs. 1.6 (IQR 0.78–5.4), P < 0.001; NLR 2.7 (IQR 2.1–3.8) vs. 2.1 (IQR 1.6–2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups.

Conclusions: Patients in SR with high CHA₂DS₂-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA₂DS₂-VASc score.

Atrial fibrillation is becoming an increasingly important problem in cardio-oncology. Specific risk factors for atrial fibrillation occurrence include type of cancer disease and anticancer drugs. Anticoagulation is often abandoned. The CHA₂DS₂-VASc and CHA₂DS₂ scores may be important not only in predicting stroke but also in mortality. The role of new direct oral anticoagulants is growing, but they need to be used in a personalized approach depending on the risk of unbeneficial interactions with cancer treatment and the risk of bleeding.

Background: The diagnosis of atrial fibrillation (AFIB) related cardiomyopathy relies on ruling out other causes for heart failure and on recovery of left ventricular (LV) function following return to sinus rhythm (SR). The pathophysiology underlying this pathology is multifactorial and not as completely known as the factors associated with functional recovery following the restoration of SR.

Objectives: To identify clinical and echocardiographic factors associated with LV systolic function improvement following electrical cardioversion (CV) or after catheter ablation in patients with reduced ejection fraction (EF) related to AFIB and normal LV function at baseline.

Methods: The study included patients with preserved EF at baseline while in SR whose LVEF had reduced while in AFIB and improved LVEF following CV. We compared patients who had improved LVEF to normal baseline to those who did not.

Results: Eighty-six patients with AFIB had evidence of reduced LV systolic function and improved EF following return to SR. Fifty-five (64%) returned their EF to baseline. Patients with a history of ischemic heart disease (IHD), worse LV function, and larger LV size during AFIB were less likely to return to normal LV function. Multivariant analysis revealed that younger patients with slower ventricular response, a history of IHD, larger LV size, and more significant deterioration of LVEF during AFIB were less likely to recover their EF to baseline values.

Conclusions: Patients with worse LV function and larger left ventricle during AFIB are less likely to return their baseline LV function following the restoration of sinus rhythm.

Background: Oral anticoagulants (OAC) reduce the risk for stroke and death from all causes in patients with non-valvular atrial fibrillation (NVAF)

Objective: To explore adherence rates of OAC among patients with NVAF in long-term use in a real-world setting and to examine patient characteristics associated with good adherence.

Methods: We conducted a population-based cohort study with members of Clalit Health Services, Israel. All patients aged ≥ 30 years with a diagnosis of NVAF before 2016 who were treated with OAC were included. We included patients who filled at least one prescription per year in the three consecutive years 2016–2018. We analyzed all prescriptions that were filled for the medications from 1 January 2017 to 31 December 2017. We considered purchasing of at least nine monthly prescriptions during 2017 as good medication adherence.

Results: We identified 26,029 patients with NVAF who were treated with OAC; 10,284 (39.5%) were treated with apixaban, 6321 (24.3%) with warfarin, 6290 (24.1%) with rivaroxaban, and 3134 (12.0%) with dabigatran. Rates of good medication adherence were 88.9% for rivaroxaban, 84.9% for apixaban, 83.6% for dabigatran, and 55.8% for warfarin (P < 0.0001). Advanced age was associated with higher adherence rates (P < 0.001). Socioeconomic status was not associated with medication adherence. Good adherence with OAC was associated with lower low density lipoprotein (LDL) cholesterol and glucose levels.

Conclusions: Adherence rates to OAC in chronic use among patients with chronic NAVF are high. Investing in OAC adherence may have a wider health impact than expected.

Background: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited.

Objectives: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban.

Methods: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence.

Results: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding.

Conclusions: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.

Background: The cold season seems to be a trigger for atrial fibrillation (AF). Some reports are controversial and demonstrate variability according to the climatic characteristics in different regions.

Objective: To analyze whether meteorological factors contribute to seasonal variation of exacerbation of AF diagnosed in patients referred to the emergency department (ED) of our hospital.

Methods: We retrospectively reviewed medical data of consecutive patients admitted to the ED with symptomatic acute onset AF from 1 January 2016 to 31 December 2018. We recorded the mean monthly outdoor temperature, barometric pressure, and relative humidity during the study period.

Results: During the study period, 1492 episodes of AF were recorded. New onset AF were 639 (42.8%) and paroxysmal atrial fibrillation (PAF) were 853 (57.2%) (P = 0.03). The number of overall admission of AF episodes was not distributed uniformly through the year. Incidence of AF episodes peaked during December and was lowest in June (P = 0.049). Of 696 episodes (46.6 %) the patients were hospitalized and for 796 (53.4%) the patients were discharged (0.01). The number of hospitalizations was not distributed uniformly through the year (P = 0.049). The highest number of hospitalizations happened in December and the lowest in May. Outdoor temperature and barometric pressure (but not relative humidity) may mediate a monthly fluctuation in AF episodes with highest number of ED visits in December and the lowest in June.

Conclusions: Meteorological conditions influence exacerbation of AF episodes and hospitalization. Outdoor temperature and barometric pressure may mediate a monthly fluctuation in AF

Background: Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for new-onset atrial fibrillation (AF) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, the optimal time frame to measure CRP for risk stratification is not known.

Objectives: To evaluate the relation between the change in CRP over time (CRP velocity [CRPv]) and new-onset AF among STEMI patients treated with primary PCI.

Methods: We included 801 STEMI patients who underwent PCI between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 hours after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements. Patient medical records were reviewed for occurrence of new-onset AF.

Results: New onset AF occurred in 45 patients (6%). Patients with new onset AF had significantly higher median CRPv (1.27 vs. 0.43 mg/l/h, P = 0.002). New-onset AF during hospitalization occurred in 3.4%, 4.5 %, and 9.1% of patients in the first, second and third CRPv tertiles, respectively (P for trend = 0.006). In a multivariable logistic regression, adjusting for clinical variables the odds ratios for new onset AF was 1.93 (95% confidence interval 1.0–3.59, P = 0.04) for patients in the third CRPv tertile.

Conclusion: CRPv might be an independent and rapidly measurable biomarker for new-onset AF following primary PCI in STEMI patients.

Background: Catheter ablation (CA) is a well-established therapeutic option for patients with recurrent symptomatic atrial fibrillation (AF). Data on gender-related differences are limited with regard to baseline characteristics and long-term success rates of catheter ablation for AF.

Methods: We analyzed a cohort of 251 consecutive patients who underwent a first catheter ablation for AF in our institute during the period 2008 through 2015. All patients were followed by regular annual clinic visits, electrocardiograms, periodic 24–48 hour Holter monitoring, and loop recorders. The primary endpoint was first recurrence of AF during 1 year of follow-up.

Results: The cohort comprised 26% women (n=65), who were older (62.1 ± 9.6 vs. 54.4 ± 11.3 years, P < 0.01) and had a higher proportion of diabetes mellitus (23.1 vs. 5.4%, P < 0.001) than male patients. No other significant differences were evident. At 1 year follow-up, the cumulative survival free of AF was significantly higher in women compared with men (83% vs. 66%, respectively, log rank P value = 0.021). Subgroup analysis showed an interaction between female and small indexed left atrial diameter (LADi < 23 mm/m²).

Conclusions: Our findings suggest that women experience a significantly lower rate of AF recurrence post-CA compared with men. This gender-related advantage appears to be restricted to women without significant left atrial enlargement. It further implies that left atrial enlargement has a stronger negative impact on post-CA AF recurrence in females than in males. Due to the relatively small sample number of females further research is warranted to validate our conclusions.