Israel Medical Association Journal

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.

Background: Reduced sensitivity to thyroid hormone (RSTH) syndrome describes a group of rare heterogeneous genetic disorders. Precise diagnosis is essential to avoid unnecessary treatment.

Objectives: To identify and characterize previously undiagnosed patients with RSTH in Israel.

Methods: Patients with suspected RSTH throughout Israel were referred for study. After clinical evaluation, genomic DNA was obtained and all coding exons of the thyroid hormone receptor beta (THRB) gene were sequenced. If mutations were found, all available blood relatives were evaluated. The common polymorphism rs2596623, a putative intronic regulatory variant, was also genotyped. Genotype/phenotype correlations were sought, and the effect of mutation status on pregnancy outcome was determined.

Results: Eight mutations (one novel; two de-novo, six dominant) were identified in eight probands and 13 family members. Clinical and genetic features were similar to those reported in other populations. Previous suggestions that rs2596623 predicts clinical features were not confirmed. There was no evidence of increased risk of miscarriage or fetal viability. Mothers carrying a THRB mutation tended to have increased gestational hypertension and low weight gain during pregnancy. Their affected offspring had increased risk of small-for-gestational age and poor postnatal weight gain.

Conclusions: Clinical heterogeneity due to THRB mutations cannot be explained by the variant rs2596623. Mothers and newborns with THRB mutations seem to be at increased risk of certain complications, such as gestational hypertension and poor intrauterine and postnatal growth. However, these issues are usually mild, suggesting that routine intervention to regulate thyroid hormone levels may not be warranted in these patients.

Background: Gender-related differences (GRD) exist in the outcome of patients with cardiac resynchronization therapy (CRT).

Objectives: To assess GRD in patients who underwent CRT.

Methods: A retrospective cohort of 178 patients who were implanted with a CRT in a tertiary center 2005–2009 was analyzed. Primary outcome was 1 year mortality. Secondary endpoints were readmission and complication rates.

Results: No statistically significant difference was found in 1 year mortality rates (14.6% males vs. 11.8% females, P = 0.7) or in readmission rate (50.7% vs. 41.2%, P = 0.3). The complication rate was only numerically higher in women (14.7% vs. 5.6%, P = 0.09). Men more often had CRT-defibrillator (CRT-D) implants (63.2% vs. 35.3%, P = 0.003) and had a higher rate of ischemic cardiomyopathy (79.2% vs. 38.2%, P < 0.001). There was a trend to higher incidence of ventricular fibrillation/ventricular tachycardia in men before CRT implantation (29.9% vs. 14.7%, P = 0.07%). A higher proportion of men upgraded from implantable cardioverter defibrillator (ICD) to CRT-D, 20.8% vs. 8.8%, P = 0.047. On multivariate model, chronic renal failure was an independent predictor of 1 year mortality (hazard ratio [HR] 3.6; 95% confidence interval [95%CI] 1.4–9.5), CRT-D had a protective effect compared to CRT-pacemaker (HR 0.3, 95%CI 0.12–0.81).

Conclusions: No GRD was found in 1 year mortality or readmission rates in patients treated with CRT. There was a trend toward a higher complication rate in females. Men were implanted more often with CRT-D and more frequently underwent upgrading of ICD to CRT-D.

Background: In recent years cardioversion of atrial fibrillation has become a routine procedure, enabling symptomatic functional improvement in most cases. However, some patients develop complications after cardioversion. Identifying these individuals is an important step toward improving patient outcome.

Objectives: To characterize those patients who may not benefit from cardioversion or who may develop complications following cardioversion.

Methods: We retrospectively analyzed 186 episodes of cardioversion in 163 patients with atrial fibrillation who were admitted to our cardiology department between 2008 and 2013 based on their clinical and echocardiographic data. Patients were divided into two groups: those with uncomplicated cardioversion, and those who developed complications after cardioversion.

Results: Of the 186 episodes, cardioversion was done in 112 men (60%) and 74 women (40%), P < 0.00001. Complications after cardioversion occurred in 25 patients (13%). These patients were generally older (72 vs. 65 years, P < 0.01), were more often diabetic (52% vs. 27%, P = 0.005), had undergone emergency cardioversion (64% vs. 40%, P = 0.01), had left ventricular hypertrophy (left ventricular mass 260 vs. 218 g, P = 0.01), had larger left atrium (left atrial volume 128 vs. 102 ml, P < 0.009), and more often died from complications of cardioversion (48% vs. 16%). They had significant mitral regurgitation (20% vs. 4%, P = 0.03) and higher pulmonary artery pressure (50 vs. 42 mm Hg, P < 0.02).

Conclusions: People with complications after cardioversion tend to be older, are more often diabetic and more often have severe mitral regurgitation. In these patients, the decision to perform cardioversion should consider the possibility of complications.

Background: Atrial fibrillation (AF) is the most common arrhythmia and a common cause of ischemic stroke. Stroke patients with AF have been shown to have a poorer neurological outcome than stroke patients without AF.

Objectives: To determine the impact of pre-existing AF on residual degree of disability in patients treated with IV thrombolysis.

Methods: In this case-control study, data of 214 stroke patients (63 with AF and 151 without AF) were collected from the National Acute Stroke Israeli Registry, a nationwide quadrennial stroke database. Stroke severity and outcome were compared using the National Institute of Health Stroke Scale (NIHSS) on admission and the modified Rankin Scale (mRS) on admission and discharge. Demographics and stroke characteristics were also compared between the groups.

Results: Stroke severity, as determined by NIHSS at admission, was higher in the AF group than the non-AF. In the group of patients who were treated with intravenous tissue plasminogen activator (tPA), more patients had favorable outcomes (mRS = 0–1 on discharge) in the non-AF group than in the AF group (P = 0.058, odds ratio = 2.217, confidence interval 0.973 to 5.05).

Conclusions: Our study suggests worse outcome in thrombolized patients with AF compared to non-AF stroke patients. Therefore, AF itself can be a poor prognostic factor for tPA sensitivity regarding the chance of revascularization and recovery after intravenous tPA.

Background: Syncope prognosis varies widely: 1 year mortality may range from 0% in the case of vasovagal events up to 30% in the presence of heart disease. 

Objectives: To assess the outcomes and prognosis of patients with implantable cardiac defibrillator (ICD) and indication of primary prevention and compare patients presenting with or without prior syncope.

Methods: We reviewed the charts of 75 patients who underwent ICD implantation with the indication of primary prevention and history of syncope and compared them to a control group of 80 patients without prior syncope. We assessed the number of ventricular tachycardia (VT), ventricular fibrillation (VF), shock, anti-tachycardia pacing (ATP), and death in each group during the follow-up.

Results: Mean follow-up was 893 days (810–976, 95% confidence interval) (no difference between groups). Patients with prior syncope had a higher ejection fraction (EF) (35.5 ± 12.6 vs. 31.4 ± 8.76, P = 0.02), more episodes of VT (21.3% vs. 3.8%, P = 0.001) and VF (8% vs. 0%, P = 0.01) and also received more electric shocks (18.7% vs. 3.8%, P = 0.004) and ATP (17.3% vs. 6.2%, P = 0.031). There were no differences in inappropriate shocks (6.7% vs. 5%, P = 0.74), in cardiovascular mortality (cumulative 5 year estimate 29.9% vs. 32.2% P = 0.97) and any death (cumulative 5 year estimate 38.1% vs. 48.9% P = 0.18) during the follow-up.

Conclusions: Syncopal patients before ICD implantation seem to have more episodes of VT/VF and shock or ATP. No mortality differences were observed