Trends in Atrial Fibrillation Management-Results from a National Multi-Center Urgent Care Network Registry.

BACKGROUND: Atrial fibrillation (AF) is a common diagnosis in patients presenting to urgent care centers (UCCs), yet there is scant research regarding treatment in these centers. While some of these patients are managed within UCCs, some are referred for further care in an emergency department (ED). OBJECTIVES: We aimed to identify the rate of patients referred to an ED and define predictors for this outcome. We analyzed the rates of AF diagnosis and hospital referral over the years. Finally, we described trends in patient anticoagulation (AC) medication use. METHODS: This retrospective study included 5873 visits of patients over age 18 visiting the TEREM UCC network with a diagnosis of AF over 11 years. Multivariate analysis was used to identify predictors for ED referral. RESULTS: In a multivariate model, predictors of referral to an ED included vascular disease (OR 1.88 (95% CI 1.43-2.45), p < 0.001), evening or night shifts (OR 1.31 (95% CI 1.11-1.55), p < 0.001; OR 1.68 (95% CI 1.32-2.15), p < 0.001; respectively), previously diagnosed AF (OR 0.31 (95% CI 0.26-0.37), p < 0.001), prior treatment with AC (OR 0.56 (95% CI 0.46-0.67), p < 0.001), beta blockers (OR 0.63 (95% CI 0.52-0.76), p < 0.001), and antiarrhythmic medication (OR 0.58 (95% CI 0.48-0.69), p < 0.001). Visits diagnosed with AF increased over the years (p = 0.030), while referrals to an ED decreased over the years (p = 0.050). The rate of novel oral anticoagulant prescriptions increased over the years. CONCLUSIONS: The rate of referral to an ED from a UCC over the years is declining but remains high. Referrals may be predicted using simple clinical variables. This knowledge may help to reduce the burden of hospitalizations.

Pathway for the Diagnosis and Management of Cardiac Amyloidosis.

The systemic amyloidoses are a broad spectrum of diseases that result from misfolding of proteins that aggregate into amyloid fibrils. In cardiac amyloidosis, amyloid fibrils accumulate in the interstitial space between cardiac myocytes causing cellular injury and impairing compliance. Current data suggest that cardiac amyloidosis is more common than previously thought. Advances in cardiac imaging, diagnostic strategies, and therapies have improved the recognition and treatment of cardiac amyloidosis. A position statement for the diagnosis and treatment of cardiac amyloidosis has been published in 2021 by the European Society of Cardiology and an expert consensus decision pathway was published in 2023 by the American College of Cardiology. These are excellent documents but quite lengthy and complex. For this reason, our team developed a novel and simple pathway to help health care providers diagnose and treat patients with cardiac amyloidosis. Our pathway starts with a section titled "suspicion" in which we provide simple clues or "red flags" that are associated with the cardiac amyloidosis phenotype. It is followed by a section titled "diagnosis," where we present in a simplified 2 × 2 format the laboratory and imaging tests that must be performed for an accurate diagnosis. In the section titled "treatment," we describe the 4 pillars in the management of patients with cardiac amyloidosis, which includes the following: heart failure treatments, management of arrhythmias, treatment of significant aortic stenosis, and appropriate selection of disease modifying therapies. Our algorithm ends with our simplified recommendation for follow-up.

Ser77Tyr transthyretin amyloidosis in Israel: Initial manifestations and diagnostic features.

OBJECTIVE: Amyloidosis due to the transthyretin Ser77Tyr mutation (ATTRS77Y) is a rare autosomal-dominant disorder, characterized by carpal-tunnel syndrome, poly- and autonomic-neuropathy, and cardiomyopathy. However, related symptoms and signs are often nonspecific and confirmatory tests are required. We describe the age and frequency of early symptoms and diagnostic features among individuals of Jewish Yemenite descent in Israel. METHODS: Records of mutation carriers were retrospectively reviewed. ATTRS77Y diagnosis was defined by the presence of amyloid in tissue and/or amyloid-related cardiomyopathy. RESULTS: We identified the Ser77Tyr mutation at the heterozygous state in 19 amyloidosis patients (mean age at diagnosis: 62 ± 5.7 years, range 49-70) and 30 amyloid-negative carriers. The probability for disease diagnosis increased from 4.4% at age 49 to 100% at 70 and occurred earlier in males. Initial symptoms preceded diagnosis by 5 ± 3.8 years (range 0-12) and were commonly sensory changes in the extremities. Erectile dysfunction predated these in 8/13 (62%) males. In two patients cardiac preceded neurological symptoms. Two patients declined symptoms. Electrophysiological studies near the time of diagnosis indicated a median neuropathy at the wrist in 18/19 (95%) and polyneuropathy in 13/19 (68%). Skin biopsy revealed epidermal denervation in 15/16 (94%) patients. Cardiomyopathy was identified in 16/19 (84%). Sensory complaints or epidermal denervations were present in 17/30 (57%) of amyloid-negative carriers and co-occurred in 10/30 (33%). INTERPRETATION: ATTRS77Y symptoms commonly occur after age 50, but may begin earlier. Median neuropathy, skin denervation and cardiomyopathy are frequently identified. Symptoms may be absent in patients and common in amyloid-negative carriers.

Peripheral Arterial Disease in Patients With Acute Coronary Syndrome: Results From a Large Real-World Registry.

BACKGROUND: Limited data exist regarding the significance of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS). METHODS: We evaluated 16,922 consecutive ACS patients who were prospectively included in a national ACS registry. The co-primary endpoint included 30 days major adverse cardiovascular event (MACE) (re-infarction, stroke, and/or cardiovascular death) and 1-year mortality. RESULTS: PAD patients were older (70±11 vs 63±13; p<0.01), male predominance (80% vs 77%; p=0.01), and more likely to sustain prior cardiovascular events. PAD patients were less likely to undergo coronary angiography (69% vs 83%; p<0.001) and revascularisation (80% vs 86%; p<0.001). Patients with PAD were more likely to sustain 30-day MACE (22% vs 14%; p<0.001) and mortality (10% vs 4.4%; p<0.001), as well as re-hospitalisation (23% vs 19%; p=0.001). After adjusting for potential confounders, PAD remained an independent predictor of 30-day MACE (odds ratio [OR], 1.6 [95% confidence interval (CI), 1.24-2.06]). Patients with compared to those without PAD had 2.5 times higher 1-year mortality rate (22% vs 9%; p<0.001). Co-existence of PAD remained an independent predictor of 1-year mortality after adjustment for potential confounders by multivariable regression analysis (OR, 1.62; 95% CI, 1.4-1.9). PAD was associated with a significant higher 1-year mortality rate across numerous sub-groups of patients including type of myocardial infarction (ST-elevation myocardial infarction vs non-ST-elevation myocardial infarction), and whether the patient underwent revascularisation. CONCLUSIONS: Acute coronary syndrome with concomitant PAD represents a high-risk subgroup that warrants special attention and a more tailored approach.

Prescribing Errors With Direct Oral Anticoagulants and Their Impact on the Risk of Bleeding in Patients With Atrial Fibrillation.

INTRODUCTION: Anticoagulants are associated with significant harm when used in error, but there are limited data on potential harm of inappropriate treatment with direct oral anticoagulants (DOACs). We conducted a matched case-control study among atrial fibrillation (AF) patients admitting the hospital with a chronic treatment with DOACs, in order to assess factors associated with the risk of major bleeding. METHODS: Patient data were documented using hospital's computerized provider order entry system. Patients identified with major bleeding were defined as cases and were matched with controls based on the duration of treatment with DOACs and number of chronic medications. Appropriateness of prescribing was assessed based on the relevant clinical guidelines. Conditional logistic regression was used to evaluate the potential impact of safety-relevant prescribing errors with DOACs on major bleeding. RESULTS: A total number of 509 eligible admissions were detected during the study period, including 64 cases of major bleeding and 445 controls. The prevalence of prescribing errors with DOACs was 33%. Most prevalent prescribing errors with DOACs were "drug dose too low" (16%) and "non-recommended combination of drugs" (11%). Safety-relevant prescribing errors with DOACs were associated with major bleeding [adjusted odds ratio (aOR) 2.17, 95% confidence interval (CI) 1.14-4.12]. CONCLUSION: Prescribers should be aware of the potential negative impact of prescribing errors with DOACs and understand the importance of proper prescribing and regular follow-up.

Prognostic significance of the frontal QRS-T angle in patients with AL cardiac amyloidosis.

INTRODUCTION: Cardiac involvement is a leading cause of morbidity and mortality in primary light chain (AL) amyloidosis. The electrocardiographic spatial QRS-T angle reflects changes in the direction of the repolarization sequence and is a powerful predictor of outcome in patients with heart failure. We examined the significance of the frontal QRS-T angle in predicting the clinical outcome in patients with AL cardiac amyloidosis. METHODS: Forty-three consecutive patients with cardiac involvement of AL amyloidosis were studied. Patients were followed for survival. RESULTS: Patient median age was 62 years, 56% were males. After a median follow up of 56 months, 16 out of 43 patients had died (37%). The median QRS-T angle was 102° (interquartile range 35-148). QRS-T angle>102° was associated with increased prevalence of lambda free light chain disease and the presence of a pleural effusion. It was also associated with increased interventricular septum thickness, smaller left ventricle end-diastolic diameter, echocardiographic myocardial sparkling texture, pericardial effusion, elevated NT-Pro-BNP and increased restrictive physiology evident by increased E/A and E/e`. A QRS-T angle>102° was a significant predictor of increased mortality by Kaplan-Meier survival analysis (71.6 ± 11.1% vs. 45.7 ± 11.1%, P = .02). A QRS-T angle>102° was an independent predictor of mortality by Cox regression analysis (HR 3.00, 95% CI 1.01-8.89, P < .05). CONCLUSIONS: The QRS-T angle is associated with indices of advanced amyloid disease and is an independent predictor of survival.

Appropriateness of direct oral anticoagulant dosing and its relation to drug levels in atrial fibrillation patients.

Direct oral anticoagulants (DOACs) are commonly administered at a level that is lower than that recommended by dose reduction criteria. This raises concern regarding the adequacy of anticoagulation achieved. To evaluate the relationship between inappropriate dosing and DOAC levels. Medical records of atrial fibrillation patients who underwent DOAC level testing during 2013-2017 were reviewed. The primary outcomes were drug levels under and above the expected steady-state range, and in the lowest and highest quartiles. Of 143 patients who underwent DOAC measurements, only 87 (60.8%) received the appropriate dose. Levels under the expected range and in the lowest quartile were found in 11.9% and 15.0% of patients treated with appropriate dosing compared to 21% and 41.5% of patients treated with inappropriately low dose. DOAC levels were above the expected range and in the highest quartile in 23.8% and 32.5% of patients treated with the appropriate dose compared to 7.1% and 9.4% treated with inappropriately low dose. In multivariate analysis, the administration of an appropriate DOAC dose was associated with a lower rate of DOAC in the lowest level (adjusted odds ratio [95% CI] 0.30 (0.12, 0.76), P = 0.011). On the other hand, appropriate dose was associated with drug levels in the highest quartile (odds ratio [95% CI] 3.77 (0.12, 0.76), P = 0.011). Treatment with inappropriately low DOAC dosing compared to appropriate dose is associated with lower DOAC levels. However, among those treated with appropriate dosing, a higher proportion had high DOAC levels above the expected range.

Early onset, non-rheumatic, group A streptococcal-associated myocarditis.

OBJECTIVES: Group A streptococcal (GAS) tonsillitis is reported as an uncommon cause of acute non-rheumatic fever (non-RF) myocarditis. The aim of this research was to study the occurrence, diagnosis, management and prognosis of this condition. METHODS: We conducted a retrospective computerised search through medical records of patients admitted to our tertiary medical center between 1998-2016 with the diagnosis of either acute rheumatic fever or non-RF streptococcal myocarditis based on criteria we developed and review the relevant literature from 1973-2016. RESULTS: We identified 283 cases diagnosed with acute myocarditis. Eight patients with non-RF GAS-myocarditis were identified, 7 of whom were men. Average age was 28.5 (22-35) years, and average latency period between onset of sore throat and chest pain 4.8 (3-10) days. Most patients presented with ST-segment elevations on the ECG and 2 underwent coronary catheterisation with presumed diagnosis of myocardial infarction. Three patients had heart failure, as documented by echocardiogram. All patients were treated with antibiotics and 6 patients received non-steroidal anti-inflammatory drugs (NSAIDs). All patients recovered with no evidence of heart failure a few months after the initial infection. One patient had a recurrent episode. CONCLUSIONS: Non-RF GAS myocarditis typically affects healthy young males and represents about 3% of all hospitalised patients with myocarditis. These patients may be mistakenly diagnosed with an acute rheumatic fever or myocardial infarction. The prognosis in generally good following treatment with antibiotics and possibly NSAIDs.

Outcomes of Patients Presenting With Clinical Indices of Spontaneous Reperfusion in ST-Elevation Acute Coronary Syndrome Undergoing Deferred Angiography.

BACKGROUND: Few data are available regarding the optimal management of ST-elevation myocardial infarction patients with clinically defined spontaneous reperfusion (SR). We report on the characteristics and outcomes of patients with SR in the primary percutaneous coronary intervention era, and assess whether immediate reperfusion can be deferred. METHODS AND RESULTS: Data were drawn from a prospective nationwide survey, ACSIS (Acute Coronary Syndrome Israeli Survey). Definition of SR was predefined as both (1) ≥70% reduction in ST-segment elevation on consecutive ECGs and (2) ≥70% resolution of pain. Of 2361 consecutive ST-elevation-acute coronary syndrome patients in Killip class 1, 405 (17%) were not treated with primary reperfusion therapy because of SR. Intervention in SR patients was performed a median of 26 hours after admission. These patients were compared with the 1956 ST-elevation myocardial infarction patients who underwent primary reperfusion with a median door-to-balloon of 66 minutes (interquartile range 38-106). Baseline characteristics were similar except for slightly higher incidence of renal dysfunction and prior angina pectoris in SR patients. Time from symptom onset to medical contact was significantly greater in SR patients. Patients with SR had significantly less in-hospital heart failure (4% versus 11%) and cardiogenic shock (0% versus 2%) (P<0.01 for all). No significant differences were found in in-hospital mortality (1% versus 2%), 30-day major cardiac events (4% versus 4%), and mortality at 30 days (1% versus 2%) and 1 year (4% versus 4%). CONCLUSIONS: Patients with clinically defined SR have a favorable prognosis. Deferring immediate intervention seems to be safe in patients with clinical indices of spontaneous reperfusion.

Heat Acclimatization Protects the Left Ventricle from Increased Diastolic Chamber Stiffness Immediately after Coronary Artery Bypass Surgery: A Lesson from 30 Years of Studies on Heat Acclimation Mediated Cross Tolerance.

During the period of 1986-1997 the first 4 publications on the mechanical and metabolic properties of heat acclimated rat's heart were published. The outcome of these studies implied that heat acclimation, sedentary as well as combined with exercise training, confers long lasting protection against ischemic/reperfusion insult. These results promoted a clinical study on patients with coronary artery disease scheduled for elective coronary artery bypass operations aiming to elucidate whether exploitation of environmental stress can be translated into human benefits by improving physiological recovery. During the 1998 study, immediate-post operative chamber stiffness was assessed in patients acclimatized to heat and low intensity training in the desert (spring in the Dead Sea, 17-33°C) vs. patients in colder weather (spring in non-desert areas, 6-19°C) via echocardiogram acquisition simultaneous with left atrial pressure measurement during fast intravascular fluid bolus administration. We showed that patients undergoing "heat acclimatization combined with exercise training" were less susceptible to ischemic injury, therefore expressing less diastolic dysfunction after cardiopulmonary bypass compared to non-acclimatized patients. This was the first clinical translational study on cardiac patients, while exploiting environmental harsh conditions for human benefits. The original experimental data are described and discussed in view of the past as well as the present knowledge of the protective mechanisms induced by Heat Acclimation Mediated Cross-tolerance.

Temporal trends and outcomes associated with atrial fibrillation observed during acute coronary syndrome: Real-world data from the Acute Coronary Syndrome Israeli Survey (ACSIS), 2000-2013.

BACKGROUND: The past decade has brought major advances in therapy of patients presenting with acute coronary syndromes (ACS). HYPOTHESIS: The outcomes of ACS patients with atrial fibrillation (AF) has improved over the years. METHODS: We evaluated time-dependent changes in clinical characteristics, management strategies, and outcomes associated with AF observed during ACS hospitalization in patients enrolled in the biannual ACS Israeli Surveys (ACSIS) between 2000 and 2013. We divided the surveys into early (2000-2006) and late (2008-2013) time periods. RESULTS: The study population comprised 13 297 ACS patients, of whom 755 (5.7%) either presented with or developed AF during the index hospitalization. The incidence of AF observed during ACS hospitalization was lower during the later period (6.2% vs 4.9%; P < 0.01). Kaplan-Meier survival analysis showed that 1-year mortality rates were significantly lower among ACS patients with and without AF who were enrolled during the later vs early survey period (log-rank P < 0.01 for the overall difference). However, AF observed among ACS patients was still associated with increased risk for in-hospital complications and 30-day and 1-year mortality during both the early and late survey periods (P < 0.05 for all comparisons). CONCLUSIONS: In 10 years, rates of AF among ACS patients have declined significantly. Yet, despite improved overall 1-year survival for patients with AF, the development of AF in this population remains an independent predictor of mortality that has not changed appreciably over the years.

Major Bleeding and Hemorrhagic Stroke With Direct Oral Anticoagulants in Patients With Renal Failure: Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Direct oral anticoagulants (DOACs) are used as an alternative for traditional antithrombotic therapy. However, the safety profile of DOACs in patients with renal failure (RF) has not been determined. METHODS: A systematic review was performed assessing the reported safety of DOACs compared with vitamin K antagonists (VKAs) in patients with RF and estimated creatinine clearance (eCrCL) < 50 mL/min and eCrCL 50 to 80 mL/min. MEDLINE, EMBASE, Cochrane, and the Clinical Trials Registry (ClinicalTrials.gov) were searched for randomized clinical trials up to November 2015. The data were pooled by using both traditional frequentist and Bayesian random effects models. RESULTS: Nine trials met the inclusion criteria. Among 94,897 participants, 54,667 (58%) had RF. Compared with VKAs, DOACs were associated with a significantly decreased risk for major bleeding in patients with eCrCL 50 to 80 mL/min (risk ratio, 0.87 [95% CI, 0.81-0.93]) and a nonsignificant decrease in the risk for major bleeding in patients with eCrCL < 50 mL/min (risk ratio, 0.83 [95% CI, 0.68-1.02]); there was evidence of significant heterogeneity. Indirect comparisons, using Bayesian network analysis, indicated that apixaban was associated with a decreased rate of major bleeding compared with other DOACs in patients with eCrCL < 50 mL/min. DOACs were associated with a significant decrease in the risk for hemorrhagic stroke compared with VKAs in patients with eCrCL < 50 mL/min and 50 to 80 mL/min. CONCLUSIONS: As a class, DOACs are associated with a reduced risk for hemorrhagic stroke compared with VKAs in patients with RF. However, DOACs may differ from each other in their relative risk for major bleeding in patients with eCrCL < 50 mL/min. TRIAL REGISTRY: PROSPERO registry; No.: CRD42014013730; URL: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014013730.

Thrombolysis followed by coronary angiography versus primary percutaneous coronary intervention in non-anterior ST-elevation myocardial infarction.

BACKGROUND: Previous studies demonstrated the superiority of primary percutaneous coronary intervention (PCI) over thrombolysis for treatment of ST-elevation myocardial infarction (STEMI); however, this advantage is less evident in low-risk populations. The aim of this study was to assess whether a strategy of thrombolysis followed by routine coronary angiography in patients with non-anterior STEMI is non-inferior to primary PCI. METHODS: Consecutive patients with non-anterior STEMI presenting within 6 hours of symptom onset who received reperfusion treatment were included. Mortality, infarct size, and in-hospital and long-term major adverse events were compared between patients treated with primary PCI to those who received thrombolysis followed by coronary angiography and intervention as needed. RESULTS: A total of 300 patients were included: 180 who received thrombolysis and 120 treated with primary PCI. No significant differences were found in mortality, infarct size, or long-term adverse events between groups. Higher rates of in-hospital recurrent ischemic events and longer hospitalization were noted in the thrombolysis group. CONCLUSIONS: The strategy of thrombolysis followed by routine coronary angiography in non-anterior STEMI patients results in major outcomes similar to primary PCI. Thrombolysis serves as a viable approach for patients presenting with non-anterior STEMI to hospitals without catheterization facilities. The optimal time between thrombolysis and coronary angiography should be within 2 days to avoid recurrent ischemia.

Post-procedural hypertension following transcatheter aortic valve implantation: incidence and clinical significance.

OBJECTIVES: This study sought to investigate the blood pressure (BP) response after transcatheter aortic valve implantation (TAVI) and its correlation with short- and mid-term clinical outcomes. BACKGROUND: TAVI is an emerging therapy for aortic stenosis patients at high surgical risk. The acute hemodynamic sequelae of this procedure and their clinical relevance are yet unclear. METHODS: Consecutive patients who underwent TAVI in a single center were prospectively monitored for BP response during 5 post-procedural days. Clinical parameters, adverse events, and medical treatment were recorded during hospitalization, at 30 days, and at 12 months after the procedure. Patients were divided according to their post-procedural BP response into 2 groups: increased BP and stable BP. RESULTS: One hundred and five patients were analyzed. Overall, systolic BP increased immediately after TAVI in the entire cohort by an average of 15 ± 31 mm Hg. This rise was sustained and led to intensification of antihypertensive treatment in 53 patients (51%); these patients were designated as the increased BP group. The increase in systolic BP after TAVI was associated with an increase in stroke volume and cardiac output and was not related to age, baseline cardiac function, or procedural outcomes. Patients with increased BP after TAVI had a significantly better prognosis with fewer adverse events in the hospital (21% vs. 62%, p < 0.01), after 30 days (30% vs. 71%, p < 0.01), and after 12 months (53% vs. 83%, p < 0.01) as compared with patients with stable BP. CONCLUSIONS: After TAVI, a substantial number of patients have a significant rise in systolic BP necessitating long-term treatment. This increase in BP is associated with an increase in cardiac output and predicts a better clinical outcome.

The incidence and prognosis of renal dysfunction following cardioversion of atrial fibrillation.

OBJECTIVE: Limited data are available regarding the incidence and clinical impact of renal dysfunction following cardioversion of atrial fibrillation. The objective of this study was to assess the incidence and implications of renal dysfunction following cardioversion of atrial fibrillation. METHODS: We conducted a nested case-control study to determine the incidence, timing, risk factors and outcome of atrial fibrillation cardioversion associated with renal dysfunction (AFCARD) in a tertiary medical center. Consecutive patients undergoing direct current cardioversion (DCCV) for atrial fibrillation in our institution during 2008-2009 with measurements of creatinine before and following cardioversion were included. AFCARD was defined as a rise in serum creatinine greater than 25% from baseline within a week following DCCV. RESULTS: One hundred and twelve patients were included in the study, of whom 19 (17%) developed AFCARD. One patient required hemodialysis. Patients with AFCARD had a higher incidence of advanced heart failure, diabetes mellitus and were more frequently treated with digoxin and enoxaparin. Patients with AFCARD had a significantly decreased survival rate at 1 year (63 vs. 92%; p < 0.001). CONCLUSIONS: AFCARD is relatively common and is associated with increased mortality. These findings suggest a role for close surveillance of renal function following DCCV.

Estrogen receptor beta gene variant is associated with vascular dementia in elderly women.

OBJECTIVE: Alzheimer's disease (AD) and vascular dementia (VaD) are the main causes of dementia. Postmenopausal estrogen deficiency was suggested as a contributor to cognitive decline; however, replacement therapy failed to prove beneficial in its prevention or therapy. Sequence variants in the estrogen receptor alpha gene (ESR1) and beta gene (ESR2) may alter the effects of estrogen. METHODS: This is a case-control association study of sporadic AD, VaD, and single-nucleotide polymorphisms in ESR1 (rs2234693 and rs9340799), the TA dinucleotide repeat in the ESR1 promoter, and the rs4986938 single-nucleotide polymorphism in ESR2. Two hundred forty-six women (118 AD, age 83 +/- 7; 60 VaD, age 82 +/- 6; and 68 cognitively intact, age 81 +/- 7) residing in nursing homes were studied. The association of genotypes and AD or VaD was determined by logistic regression analysis adjusted for age and ethnic origin. RESULTS: An association of VaD and ESR2 rs4986938 was found. Carriers of each A allele had a 1.7 increased risk compared to carriers of the G allele (odds ratio 1.71, 95% confidence interval 1-2.95). The ApoE epsilon 4 allele was associated with AD (odds ratio 3.35, confidence interval 1.44-7.82), but not with VaD. No association of AD or VaD with ESR1 genotypes or haplotypes was detected. CONCLUSIONS: The ESR2 rs4986938 polymorphism is associated with susceptibility for VaD in elderly Jewish women. These results need to be confirmed in replicate studies in other populations.

Blood pressure and heart rate variability in patients on conventional or sodium-profiling hemodialysis.

BACKGROUND: Autonomic nervous system dysfunction and dialysate sodium (Na) concentration are believed to play a role in the pathogenesis of hemodialysis-related hypertension. The present study was undertaken to determine whether increases in blood pressure in hemodialysis patients are associated with changes in heart rate variability (HRV), a measure of the autonomic nervous system function, and long-term exposure to increased dialysate Na concentration. METHODS: Baseline clinical, biochemical data and HRV of patients undergoing increased Na profiling dialysis (High-Na, n = 9) and on conventional treatment (Control, n = 11) were compared with those obtained after one year of study. RESULTS: After one year, the mean predialysis systolic blood pressure (SBP) increased in seven patients of the High-Na and in five of the Control group, and decreased or remained unchanged in the remaining subjects. Initial HRV was significantly higher in patients with increased SBP, and it increased further in these patients after one year. At the end of the study, post-dialysis plasma Na, osmolality, and weight gains were significantly higher in the High-Na group. No significant correlation, however, was found between individual changes in intradialytic sodium elimination and the alterations in blood pressure. CONCLUSION: These data suggest that the dialysate sodium concentration, a most important determinant of interdialytic weight gain and fluid balance, is only partly correlated with long-term changes in blood pressure. An increased blood pressure over time may develop in a subset of hemodialysis patients with higher HRV, suggestive of increased sympathetic activity.

Age-related changes in echocardiographic measurements: association with variation in the estrogen receptor-alpha gene.

Left ventricular (LV) mass and other LV measures have been shown to be heritable. In this study we hypothesized that functional variation in the gene coding for estrogen receptor-alpha (ESR1), known for mediating the effect of estrogens on myocardium, is associated with age-related changes in LV structure. Four genetic markers (ESR1 TA repeat; rs2077647, or +30T>C; rs2234693, or PvuII; and rs9340799, or XbaI) were genotyped in 847 unrelated individuals (488 women) from the Framingham Offspring Study, who attended 2 examination cycles 16 years apart (mean ages at first examination: 43+/-9 years; at follow-up: 59+/-9 years). ANCOVA was used to assess the association of polymorphisms and their haplotypes with cross-sectional measurements and longitudinal changes in LV mass, wall thickness, end-diastolic and end-systolic internal diameter, and fractional shortening after adjustment for factors known to influence these variables. Changes over time were detected for all of the LV measurements (P ranging from <0.0001 to 0.02), except for fractional shortening in men. The SS genotype of the ESR1 TA repeat polymorphism in the promoter region was associated with longitudinal changes in LV mass and LV wall thickness (P ranging from 0.0006 to 0.01). Moreover, the TA[S]-+30[T]-PvuII[T]-XbaI[A] haplotype (frequency: 47.5%) was associated with greater LV changes as compared with the TA[L]-+30[C]-PvuII[C]-XbaI[G] haplotype (frequency: 31.8%). Our results are consistent with the hypothesis that common ESR1 polymorphisms are significantly associated with age-related changes in LV structure. Understanding the mechanisms predisposing to unfavorable LV remodeling of the heart with advancing age may aid in the discovery of new therapeutic targets for the prevention of heart failure.

Acute coronary syndrome vs nonspecific troponin elevation: clinical predictors and survival analysis.

BACKGROUND: Although troponin is considered a specific marker for the diagnosis of acute coronary syndrome (ACS), recent studies have shown troponin elevation in a variety of nonischemic conditions. Our aim was to determine the predictors for the diagnosis of ACS in the presence of an abnormal troponin level. METHODS: All patients with abnormal troponin T levels were analyzed. Demographic and clinical data were collected and death was recorded. The study group was divided into 2 subgroups: ACS vs nonthrombotic troponin elevation. A multivariate logistic regression analysis was performed to define variables that predict the diagnosis of ACS. The positive predictive value (PPV) for ACS diagnosis was calculated, and a survival analysis was performed. RESULTS: During the study period, 615 patients had elevated troponin T levels. Only 326 patients (53%) received a main diagnosis of ACS, while 254 (41%) had nonthrombotic troponin elevation; for 35 patients (6%), the diagnosis was not conclusive. Positive predictors for the diagnosis of ACS were age between 40 and 70 years, history of hypertension or ischemic heart disease, normal renal function, and a troponin T level higher than 1.0 ng/mL. The overall PPV of troponin T for ACS diagnosis was only 56% (95% CI, 52%-60%). The PPV of troponin T level higher than 1.0 ng/mL in the presence of normal renal function was 90% but was as low as 27% for values of 0.1 to 1.0 ng/mL for elderly patients with renal failure. In-hospital and long-term survival rates were significantly better (P<.001) for patients with ACS. CONCLUSIONS: Nonspecific troponin elevation is a common finding among hospitalized patients and correlates with worse prognosis. The diagnosis of myocardial infarction should still mostly be based on the clinical presentation. The predictors and algorithm suggested in this study might increase the diagnostic accuracy of ACS and direct the appropriate treatment.

Impact of follow-up on the success rate of the cryosurgical maze procedure in patients with rheumatic heart disease and enlarged atria.

OBJECTIVES: The most important predictors for failure of the maze procedure are long standing atrial fibrillation (AF), rheumatic heart disease (RHD), and enlarged atria. It is well documented, however, that some patients have recurrence of atrial arrhythmia only late in follow-up. The aims of this study are to assess the effectiveness of the maze procedure and late cardioversion (pharmacologic or electrical) in patients wtih an increased risk for procedure failure. PATIENTS AND METHODS: Fifty-five patients with AF, enlarged left atrium (>5 cm), and/or RHD were enrolled in the study. Cryosurgery was performed on all patients and was combined with bipolar radiofrequency in the last four patients. The lesion pattern resembles the maze procedure. A follow-up was completed on all patients (24.5 +/- 9.6 months with a range of 3-39 months). RESULTS: The operative mortality was 3.7% (2 patients), both deaths unrelated to the maze procedure. Ninety-eight percent of patients were free of AF upon discharge, with an 11% incidence of early pacemaker implantation. In the first three months postoperatively, 53% of the patients experienced intermittent atrial arrhythmia. Four patients were recorded with permanent AF in late follow-up. The only predictor for late AF (>3 months of follow-up) was perioperative AF. Atrial size, RHD, and AF duration did not predict late failure. CONCLUSIONS: The maze procedure can be applied with high success rate in patients with RHD, enlarged atria, and long-standing AF. In our experience many of the late recurrences were recorded late in the follow-up and were treated successfully with antiarrhythmic drugs and/or cardioversion. Therefore a close follow-up is required to enhance the success rate of the procedure.