Amiodarone and pulmonary toxicity in atrial fibrillation: a nationwide Israeli study.

BACKGROUND AND AIMS: Amiodarone-related interstitial lung disease (ILD) is the most severe adverse effect of amiodarone treatment. Most data on amiodarone-related ILD are derived from periods when amiodarone was given at higher doses than currently used. METHODS: A nationwide population-based study was conducted among patients with incident atrial fibrillation (AF) between 1 December 1999 and 31 December 31 2021. Amiodarone-exposed patients were matched 1:1 with controls unexposed to amiodarone based on age, sex, ethnicity, and AF diagnosis duration. The final patient cohort included only matched pairs where amiodarone therapy was consistent throughout follow-up. Directed acyclic graphs and inverse probability treatment weighting (IPTW) modelling were used. Patients with either prior ILD or primary lung cancer (PLC) were excluded. The primary outcome was the incidence of any ILD. Secondary endpoints were death and PLC. RESULTS: The final cohort included 6039 amiodarone-exposed patients who were matched with unexposed controls. The median age was 73.3 years, and 51.6% were women. After a mean follow-up of 4.2 years, ILD occurred in 242 (2.0%) patients. After IPTW, amiodarone exposure was not significantly associated with ILD [hazard ratio (HR): 1.45, 95% confidence interval (CI): 0.97, 2.44, P = 0.09]. There was a trivial higher relative risk of ILD among amiodarone-exposed patients between Years 2 and 8 of follow-up [maximal risk ratio (RR): 1.019]. Primary lung cancer occurred in 97 (0.8%) patients. After IPTW, amiodarone was not associated with PLC (HR: 1.18, 95% CI: 0.76, 2.08, P = 0.53). All-cause death occurred in 2185 (18.1%) patients. After IPTW, amiodarone was associated with reduced mortality risk (HR: 0.65, 95% CI: 0.60, 0.72, P < 0.001). The results were consistent across a variety of sensitivity analyses. CONCLUSION: In a contemporary AF population, low-dose amiodarone was associated with a trend towards increased risk of ILD (15%-45%) but a clinically negligible change in absolute risk (maximum of 1.8%), no increased risk of PLC, and a lower risk of all-cause mortality.

Estimated glomerular filtration rate and the risk of stroke in individuals with diabetes mellitus and atrial fibrillation insight from a large contemporary population study.

BACKGROUND: Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Impaired renal function (IRF) increases the risk of stroke as well, but this finding is not consistent among all studies. Our aim was to assess the incidence rates and risk of ischemic stroke and mortality by baseline Estimated Glomerular Filtration Rate (eGFR) levels Among individuals with AF and DM. METHODS: A prospective, historical cohort study using the Clalit Health Services electronic medical records database. Among patients with AF and DM, we compared three groups according to eGFR levels: eGFR ≥ 60, between 30 and 60, and ≤ 30 (mL/min/1.73m2). RESULTS: A total of 17,567 cases were included in the final analysis; of them, 11,013 (62.7%) had eGFR ≥ 60, 4930 (28%) had eGFR between 30 and 60, and 1624 (9.24%) with eGFR ≤ 30. The incidence of stroke per 100 person-years in the three study groups was: 1.88, 2.69, and 3.34, respectively (p < 0.001). IRF was associated with increased risk of stroke in univariate analysis, but not after multivariate adjustment (Adjusted Hazard Ratio (AHR) 0.96 {95%CI; 0.74-1.25} for eGFR 30-60 and 0.96 {95%CI; 0.60-1.55} for eGFR ≤ 30). Mortality per 100 person-years was 10.78, 21.49, and 41.55, respectively (p < 0.001). IRF was associated with increased mortality risk in univariate analysis, as well as in multivariate analysis (AHR 1.08 {95%CI; 0.98-1.18} for eGFR 30-60, and 1.59 {95%CI; 1.37-1.85} for eGFR ≤ 30. CONCLUSION: In patients with NVAF and DM, IRF was not associated with an increased risk of stroke, but severe IRF (eGFR ≤ 30) was associated with increased mortality risk.

Use of oral anticoagulation therapy in the first 3 months after the diagnosis of atrial fibrillation in Israel: A population-based study.

INTRODUCTION: Oral anticoagulation (OAC) therapy reduces the risk of ischemic stroke in patients with atrial fibrillation (AF) while increasing the risk of bleeding. Recently, non-vitamin K antagonist oral anticoagulants (NOACs) have become available with lower rates of intracranial bleeding, and some of them have presented a reduced risk of major bleeding. The purpose of this study is to evaluate the change in purchasing patterns of OACs (both warfarin and NOACs) over time in patients with AF according to stroke and bleeding risk, in the first 3 months after diagnosis. METHODS AND RESULTS: We conducted a historical cohort study using the Clalit Health Services electronic medical records database. The study population included all members aged ≥21 years, with a new diagnosis of nonvalvular AF between 2008 and 2015. A total of 58 385 cases were identified. The mean age was 73.1 (±14.1) years, and 52.3% of the patients were women. The median CHA2 DS2 -VASc score was 4 (interquartile range, 3-5). OACs were purchased by 19 705 patients (33.8%) within the first 3 months of first diagnosis of AF, with patients at higher embolic risk as stratified by the CHA2 DS2 -VASc score and having higher purchasing rates (37.1%). Between 2008 and 2010, 29% of patients purchased a vitamin K antagonist, the only available OAC at the time. OAC purchasing increased to 41.4% between 2014 and 2015, with half of the patients purchasing an NOAC. CONCLUSION: In this real-world, population-based cohort study of patients with newly diagnosed AF, we found a lower than expected rate of OAC prescription within 3 months of diagnosis but an encouraging increase in OAC purchasing over time. The use of NOACs has risen exponentially within just a few years, accounting for a greater pool of patients with being prescribed an OAC.

The impact of Heart Team discussion on decision making for coronary revascularization in patients with complex coronary artery disease.

BACKGROUND AND AIM: Revascularization guidelines support routine Heart Team (HT) discussion of appropriate patients. The effect of HT on decision making and clinical outcomes has not been explored. The aim of our study is to investigate the impact of the HT on the mode and delay to revascularization. METHODS: We compared data from a prospective cohort of consecutive patients with multivessel coronary artery disease (CAD) referred for HT discussion between 2016 and 2017 (HT group) with a historic control group of patients matched according to clinical and angiographic characteristics treated between 2005 and 2015 (No HT group). RESULTS: There were 93 patients in each group. The HT group and the No HT groups had a similar rate of ACS as well as cardiovascular risk factors and significant left ventricular (LV) dysfunction. No difference was observed in the mean Society of Thoracic Surgery score (2.5 ± 3 vs 3 ± 3; P = .32) and the mean SYNTAX score was low and similar in both groups (21 ± 6 vs 19 ± 6; P = .59). The treatment recommendations changed greatly, with 63% of patients being referred for coronary artery bypass grafting (CABG) after HT discussion but only 23% in the No HT group (P < .01). HT discussion led to a significant delay to PCI (8 ± 5 vs 1.8 ± 4 days; P = .02), while surgical revascularization times were not affected. CONCLUSION: HT discussion in patients with multivessel CAD was associated with an increased referral to CABG but led to a significant delay in revascularization by angioplasty. The impact of these findings on patient satisfaction and outcome should be further investigated.

Relation of Hemoglobin A1C Levels to Risk of Ischemic Stroke and Mortality in Patients With Diabetes Mellitus and Atrial Fibrillation.

Diabetes mellitus (DM) is associated with an increased risk of complications in atrial fibrillation (AF). This study aimed to assess the incidence and risks of ischemic stroke and mortality according to baseline HbA1c levels in patients with DM and AF. We conducted a cohort study using Clalit Health Services electronic medical records. The study population included all Clalit Health Services members aged ≥25 years, with the first diagnosis of AF between January 1, 2010, and December 31, 2016, who had a diagnosis of DM. The risk of stroke and all-cause death were compared according to HbA1c levels at the time of AF diagnosis: <7.0%, between 7% and 9%, and ≥9%. A total of 44,451 patients with DM and AF were identified. The median age was 75 years (interquartile 65 to 83), and 52.5% were women. During a mean follow-up of 38 months, higher levels of HbA1c were associated with an increased risk of stroke with a dose-dependent response when compared with patients with HbA1c <7% (Adjusted hazard ratio [aHR] =1.30 [95% confidence interval 1.10 to 2.05] for levels between 7% and 9% and 1.60 (95% confidence interval 1.25 to 2.03) for HbA1c >9%, even after adjusting for CHA2DS2-Vasc risk factors and use of oral anticoagulants. The risk for overall mortality was significantly higher in the HBA1C >9% group (aHR = 1.17 [1.07 to 1.28]). In conclusion, in this cohort of patients with AF and DM, HbA1c levels were associated with the risk of stroke in a dose-dependent manner even after accounting for other recognized risk factors for stroke.

Pre-Diabetes Increases Stroke Risk in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Diabetes mellitus (DM) increases the risk of embolism in nonvalvular atrial fibrillation (NVAF). The association between pre-diabetes and risk of ischemic stroke has not been studied separately in this population. OBJECTIVES: The purpose of this study was to evaluate whether pre-diabetes is associated with increased risk of stroke and death in patients with NVAF. METHODS: We conducted a historical cohort study using the Clalit Health Services electronic medical records. The study population included all members aged ≥25 years, with a first diagnosis of NVAF between January 1, 2010, and December 31, 2016. We compared 3 groups of individuals: those with pre-diabetes, those with diabetes, and normoglycemic patients. RESULTS: A total of 44,451 cases were identified. The median age was 75 years, and 52.5% were women. During a mean follow-up of 38 months, the incidence rates of stroke (per 100 person-years) were: 1.14 in normoglycemic individuals, 1.40 in those with pre-diabetes, and 2.15 in those with diabetes. In both univariate and multivariate analyses, pre-diabetes was associated with an increased risk of stroke compared with normoglycemic persons (adjusted hazard ratio [adjHR]: 1.19; 95% confidence interval [CI]: 1.01 to 1.4) even after adjustment for CHA2DS2-Vasc risk factors and use of anticoagulants, while diabetes conferred an even higher risk (vs. normoglycemia (adjHR: 1.56; 95% CI: 1.37 to 1.79). The risk for mortality was higher for individuals with diabetes (adjHR: 1.47; 95% CI: 1.41 to 1.54) but not for those with pre-diabetes (adjHR: 0.98; 95% CI: 0.92 to 1.03). CONCLUSIONS: In this cohort of patients with incident NVAF, pre-diabetes was associated with an increased risk of stroke even after accounting for other recognized risk factors.

A Population-based Study of Peripartum Cardiomyopathy in Southern Israel: Are Bedouin Women a New High-risk Group?

OBJECTIVES: Peripartum cardiomyopathy (PPCM) is a serious complication of pregnancy. Studies investigating the risk factors that worsen outcomes have yielded conflicting results. The goals of this study were to describe the clinical and echocardiographic characteristics of PPCM in a single tertiary center and to determine the prognostic factors associated with persistence of left ventricular (LV) dysfunction in these women. STUDY DESIGN: This retrospective cross-sectional population-based cohort study included all patients with PPCM confirmed by echocardiography who delivered at our center from 2004 to 2014. Two groups were compared to determine long-term maternal outcome: (1) those who recovered normal LV function; and (2) those with residual systolic LV dysfunction. RESULTS: There were 148,994 deliveries during the study period. Of these, 89,196 patients were Bedouin and 59,798 were non-Bedouin. Forty-six patients met the PPCM study inclusion criteria. The PPCM prevalence for the total deliveries was 1:3,239. The PPCM prevalence among Bedouin patients was 1:2,787 versus non-Bedouin patients of 1:4,983 (P=0.037). None of the women had pre-existing chronic hypertension, and there was no maternal death. Patients who had severe or moderate LV dysfunction at the clinical presentation of PPCM were less likely to regain normal LV function than those with mild dysfunction (81.2% versus 56.7%, P=0.009). Based on initial echocardiogram, a trend toward residual LV dysfunction was noted in patients with a dilated left ventricle as compared to those with a non-dilated left ventricle (18.8% versus 6.7%, P=0.32). A hypokinetic right ventricle was found in 15.2% of the women who suffered from PPCM. CONCLUSION: In our cohort, Bedouin women may be at increased risk for PPCM, and patients with severe LV dysfunction have a lower chance of recovery from PPCM.

Peripartum cardiomyopathy is associated with increased uric acid concentrations: A population based study.

BACKGROUND: Peri-partum cardiomyopathy (PPCM) is a clinical heart failure that usually develops during the final stage of pregnancy or the first months following delivery. High maternal serum uric acid concentrations have been previous associated with heart failure and preeclampsia. OBJECTIVES: 1) To explored the clinical characteristics of PPCM patients; and 2) to determine the association between maternal serum uric acid concentrations and PPCM. METHODS: This is a retrospective population based case control study. Cases and controls were matched 1:4 (for gestational age, medical history of cardiac conditions and creatinine); conditional logistic regression was used to identify clinical parameters that were associated with PPCM. RESULTS: The prevalence of peripartum cardiomyopathy at our institution was 1-3832 deliveries (42/160,964). In a matched multivariate analysis high maternal serum uric acid concentrations were associated with PPCM (O.R 1.336, 95% C.I 1.003-1.778). Uric acid concentrations were higher within the Non-Jewish patients and mothers of male infant with PPCM in compare to those without PPCM (p value 0.003 and 0.01 respectively). CONCLUSION: PPCM patients had increased maternal serum uric acid concentrations. This observation aligns with previous report regarding the increased uric acid concentration in women with preeclampsia and congestive heart failure, suggestive of a common underlying mechanism that mediates the myocardial damage.

Treating the elderly diabetic patient: special considerations.

The prevalence of diabetes is rising in the >65 year-old group. The challenge of defining the goals of therapy arises from the heterogeneity of the aging process and the sparse clinical data in this patient population. In light of these challenges, the clinician should be aware of the pitfalls of caring for the older diabetic patient and prioritize an individualized treatment plan to ensure an optimal glycemic control, without placing the patient at unnecessary risk. We present a review of the current guidelines and literature that deal specifically with the treatment of the older diabetic patient in order to establish the principles of treatment in this age group and help the clinician make decisions regarding the care of these patients.

New approaches to the use of insulin in patients with diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is one of the most common and serious acute complications of diabetes and is a significant cause of morbidity and mortality. In the last decade the mortality rate from DKA has declined because of greater recognition and improvements in its management. The current available guidelines state that the most effective means of insulin delivery during DKA is a continuous infusion of regular insulin, usually referred to as continuous low-dose insulin infusion. However, the cost of this treatment is usually quite high, because patients are required to be admitted to an intensive care unit in order to be monitored closely. New analogs of human insulin that have a rapid onset of action have become available in the past decade and represent potential alternatives to the use of regular insulin in the treatment of DKA. In several trials it has been demonstrated that the use of subcutaneous rapid-acting insulin analogs represents a safe, cost-effective and technically simpler treatment that precludes intensive care unit admission without significant differences in outcome in the management of patients with mild to moderate, uncomplicated DKA. The long-acting insulin analog may have a role in facilitating the transition from continuous intravenous insulin infusion to subcutaneous maintenance therapy in patients with DKA. This avoids rebound hyperglycaemia and ketogenesis when intravenous insulin is stopped and may avoid excess length of stay.