The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis.

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.

Risks of Right Heart Catheterization and Right Ventricular Biopsy: A 12-year, Single-Center Experience.

OBJECTIVE: To study the incidence of complications when undergoing right heart catheterization (RHC) and right ventricular biopsy (RVB). METHODS: Complications following RHC and RVB are not well reported. We studied the incidence of death, myocardial infarction, stroke, unplanned bypass, pneumothorax, hemorrhage, hemoptysis, heart valve repair/replacement, pulmonary artery perforation, ventricular arrhythmias, pericardiocentesis, complete heart block, and deep vein thrombosis (primary endpoint) following these procedures. We also adjudicated the severity of tricuspid regurgitation and causes of in-hospital death following RHC. Diagnostic RHC procedures, RVB, multiple right heart procedures alone or combined with left heart catheterization, and complications from January 1, 2002, through December 31, 2013, were identified using the clinical scheduling system and electronic records at Mayo Clinic, Rochester, Minnesota. International Classification of Diseases, Ninth Revision billing codes were used. Registration was queried to identify all-cause mortality. All clinical events and echocardiograms for worsening tricuspid regurgitation were reviewed and adjudicated. RESULTS: A total of 17,696 procedures were identified. Procedures were categorized into those undergoing RHC (n=5556), RVB (n=3846), multiple right heart catheterization (n=776), and combined right and left heart catheterization procedures (n=7518). Primary endpoint was seen in 21.6 and 20.8 of 10,000 procedures for RHC and RVB, respectively. There were 190 (1.1%) deaths during hospital admission and none was related to the procedure. CONCLUSION: Complications following diagnostic RHC and RVB are seen in 21.6 and 20.8 procedures, respectively, of 10,000 procedures and all deaths were secondary to acute illness.

Prognostic Risk Stratification of Patients with Moderate Aortic Stenosis.

BACKGROUND: Currently risk stratification of moderate aortic stenosis (AS) is still incipient. The aim of this study was to identify prognostic factors in patients with moderate AS. METHODS: The prognosis of patients with moderate AS (1 < aortic valve area ≤ 1.5 cm2) stratified by left ventricular ejection fraction (LVEF; 50%), stroke volume index (SVI; 35 mL/m2), and elevated E/e' ratio (average, 14) was compared with that of the age- and sex-matched general population. RESULTS: Of 696 patients (median age, 77 years; aortic valve area 1.3 cm2; 57% men), 279 (40%) died during a median follow-up period of 3.4 years. Mortality was higher in patients with moderate AS than reference (mortality ratio, 2.43; 95% CI, 2.17-2.72). LVEF < 50%, SVI < 35 mL/m2, and elevated E/e' ratio were present in 113 (17%), 54 (8%), and 330 (54%) patients; mortality ratios were 3.89 (95% CI, 3.07-4.85), 6.40 (95% CI, 4.57-8.71), and 2.58 (95% CI, 2.21-3.00), respectively. Even if LVEF or SVI was preserved, the mortality ratio was more than twice than reference (P < .001), but elevated E/e' ratio could discriminate additional patients at higher risk (hazard ratio [HR], 2.71; 95% CI, 1.88-3.91). Two hundred one patients (29%) underwent aortic valve replacement at a median of 2.3 years after the diagnosis of moderate AS. LVEF < 50% (HR, 2.98; 95% CI, 1.39-6.56), SVI < 35 mL/m2 (HR, 3.34; 95% CI, 1.02-10.90) and elevated E/e' ratio (HR, 2.73; 95% CI, 1.26-5.94) were all associated with worse prognosis even if aortic valve replacement was performed. CONCLUSIONS: In patients with moderate AS, those with decreased LVEF and/or SVI are at high risk. Even if these parameters are preserved, patients with elevated E/e' ratios are at intermediate risk. Further investigation is warranted to assess whether earlier intervention could improve outcomes and reduced cardiac-related death among patients at high and intermediate risk.

Left Ventricular Global Longitudinal Strain Is Associated With Long-Term Outcomes in Moderate Aortic Stenosis.

BACKGROUND: Left ventricular global longitudinal strain (GLS) is associated with long-term outcomes of patients with severe aortic stenosis. However, its prognostic value in patients with moderate aortic stenosis remains unknown. METHODS: Patients diagnosed with moderate aortic stenosis (1.0< aortic valve area ≤1.5 cm2) and left ventricular ejection fraction ≥50% were identified. GLS was assessed by 2-dimensional strain imaging using speckle-tracking method. All-cause mortality was assessed according to the median GLS value. RESULTS: Two hundred eighty-seven patients were included (median age 76 years; 47% male). Mean aortic valve area was 1.25 cm2, left ventricular ejection fraction 62%, and median GLS -15.2%. During a median follow-up of 3.9 years, there were 103 deaths (36%). Mortality was higher in patients with GLS>-15.2% (hazard ratio 2.62 [95% CI 1.69-4.06]) compared with patients with GLS ≤-15.2% even after adjusting for confounders. Mortality rates at 1, 3, 5 years were 21%, 35%, 48%, respectively, in patients with GLS >-15.2%, and 6%, 15%, 19% in those with GLS ≤-15.2%. Even among those with left ventricular ejection fraction ≥60%, GLS discriminated higher-risk patients (P=0.0003). During follow-up, 106 (37%) patients underwent aortic valve replacement with median waiting-time of 2.4 years, and their survival was better than patients without aortic valve replacement. Among those patients undergoing aortic valve replacement, prognosis was still worse in patients with GLS >-15.2% (P=0.04). Mortality rates at 1, 3, 5 years were 2%, 10%, 20%, respectively, in patients with GLS >-15.2% and 2%, 5%, 6% in those with GLS ≤-15.2%. CONCLUSIONS: Impaired GLS in moderate aortic stenosis patients is associated with higher mortality rates even among those undergoing aortic valve replacement.

Is Infection an Independent Risk Factor for Venous Thromboembolism? A Population-Based, Case-Control Study.

BACKGROUND: The independent association of recent infection with venous thromboembolism is uncertain. The study aims were to test both overall infection (site unspecified) and specific infection sites as potential risk factors for deep vein thrombosis and pulmonary embolism adjusting for other known venous thromboembolism factors. METHODS: By using Rochester Epidemiology Project resources, we identified all Olmsted County, Minnesota, residents with objectively diagnosed incident deep vein thrombosis or pulmonary embolism over the 13-year period 1988 to 2000 (cases; n = 1303) and 1 to 2 residents without venous thromboembolism matched to each case on age, sex, and incident venous thromboembolism date (controls; n = 1494). Using conditional logistic regression, we tested recent infection and infection site(s) for an association with venous thromboembolism, adjusting for body mass index, smoking, current/recent hospitalization with/without surgery, nursing home confinement, active cancer, trauma/fracture, leg paresis, prior superficial vein thrombosis, transvenous catheter/pacemaker, ischemic heart disease, congestive heart failure, chronic lung or renal disease, serious liver disease, asthma, diabetes mellitus, hormone therapy, and pregnancy/postpartum. RESULTS: A total of 513 cases (39.4%) and 189 controls (12.7%) had an infection in the previous 92 days (odds ratio, 4.5; 95% confidence interval, 3.6-5.5; P < .0001). In a multivariable analysis adjusting for common venous thromboembolism risk factors, pneumonia and symptomatic urinary tract, oral, intra-abdominal, and systemic bloodstream infections were associated with significantly increased odds of venous thromboembolism. CONCLUSIONS: Infection as a whole and specific infection sites in particular are independent risk factors for venous thromboembolism and should be considered as potential indications for venous thromboembolism prophylaxis.

Temporal Trends of Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging in Patients With Coronary Artery Disease: A 22-Year Experience From a Tertiary Academic Medical Center.

BACKGROUND: There has been a gradual decline in the prevalence of abnormal stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging studies among patients without history of coronary artery disease (CAD). The trends of SPECT studies among patients with known CAD have not been evaluated previously. METHODS AND RESULTS: We assessed the Mayo Clinic nuclear cardiology database for all stress SPECT tests performed between January 1991 and December 2012 in patients with history of CAD defined as having previous myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. The study cohort was divided into 5 time periods: 1991 to 1995, 1996 to 2000, 2001 to 2005, 2006 to 2010, and 2011 to 2012. There were 19 373 patients with a history of CAD who underwent SPECT between 1991 and 2012 (mean age, 66.2±10.9 years; 75.4% men). Annual utilization of SPECT in these patients increased from an average of 495 tests per year in 1991 to 1995 to 1425 in 2003 and then decreased to 552 tests in 2012 without evidence for substitution with other stress modalities. Asymptomatic patients initially increased until 2006 and then decreased. Patients with typical angina decreased, whereas patients with dyspnea and atypical angina increased. High-risk SPECT tests significantly decreased, and the percentage of low-risk SPECT tests increased despite decreased SPECT utilization between 2003 and 2012. Almost 80% of all tests performed in 2012 had a low-risk summed stress score compared with 29% in 1991 (P<0.001). CONCLUSIONS: In Mayo Clinic, Rochester, annual SPECT utilization in patients with previous CAD increased between 1992 and 2003, but then decreased after 2003. High-risk SPECT tests declined, whereas low-risk tests increased markedly. Our results suggest that among patients with a history of CAD, SPECT was being increasingly utilized in patients with milder CAD. This trend parallels reduced utilization of other stress modalities, coronary angiography, reduced smoking, and greater utilization of optimal medical therapy for prevention and treatment of CAD.

Effect of a near-universal hospitalization-based prophylaxis regimen on annual number of venous thromboembolism events in the US.

The annual number of US venous thromboembolism (VTE) events, the number of potentially preventable events, and the effect of hospitalization-based prophylaxis are uncertain. We estimated VTE attack (incident plus recurrent VTE) rates and the total annual number of US VTE events related and unrelated to hospitalization using Rochester Epidemiology Project resources to identify all Olmsted County, Minnesota, residents with incident or recurrent VTE over the 6-year period 2005-2010. The average annual VTE attack rates related and unrelated to hospitalization were 282 and 8 per 10 000 person-years, respectively. The estimated average number of US VTE events was 495 669 per year (48% unrelated to hospitalization). Among Olmsted County residents hospitalized at a Mayo Clinic hospital from 2005 to 2010, the proportion of patients receiving VTE prophylaxis or with an indication that prophylaxis was unnecessary increased from ∼40% in 2005 to ∼90% by 2010. The annual age- and sex-adjusted hospitalization-related (in-hospital) VTE attack rates from 2005 to 2010 ranged from 251 to 306 (1155 to 1751) per 10 000 person-years (bed-years) and did not change significantly. The median durations of hospitalization and in-hospital prophylaxis were 3 days and 70 hours, respectively. A total of 75% of VTE events occurred after hospital discharge, with a 19.5-day median time to VTE. Additional efforts are needed to identify the individual inpatient and outpatient at high risk for incident and recurrent VTE and target (longer duration) primary and secondary prophylaxis to high-risk individuals who would benefit most.

Reasons for the persistent incidence of venous thromboembolism.

Reasons for trends in venous thromboembolism (VTE) incidence are uncertain. It was our objective to determine VTE incidence trends and risk factor prevalence, and estimate population-attributable risk (PAR) trends for each risk factor. In a population-based cohort study of all residents of Olmsted County, Minnesota from 1981-2010, annual incidence rates were calculated using incident VTE cases as the numerator and age- and sex-specific Olmsted County population estimates as the denominator. Poisson regression models were used to assess the relationship of crude incidence rates to year of diagnosis, age at diagnosis, and sex. Trends in annual prevalence of major VTE risk factors were estimated using linear regression. Poisson regression with time-dependent risk factors (person-years approach) was used to model the entire population of Olmsted County and derive the PAR. The age- and sex-adjusted annual VTE incidence, 1981-2010, did not change significantly. Over the time period, 1988-2010, the prevalence of obesity, surgery, active cancer and leg paresis increased. Patient age, hospitalisation, surgery, cancer, trauma, leg paresis and nursing home confinement jointly accounted for 79 % of incident VTE; obesity accounted for 33 % of incident idiopathic VTE. The increasing prevalence of obesity, cancer and surgery accounted in part for the persistent VTE incidence. The PAR of active cancer and surgery, 1981-2010, significantly increased. In conclusion, almost 80 % of incident VTE events are attributable to known major VTE risk factors and one-third of incident idiopathic VTE events are attributable to obesity. Increasing surgery PAR suggests that concurrent efforts to prevent VTE may have been insufficient.

Cardiac Structural Changes and Long-Term Survival in Patients With Prominent Thebesian Veins.

Although rare, numerous case reports suggest that Thebesian veins confer increased morbidity and mortality. No study has evaluated their effects on cardiac structure or long-term patient outcomes. Patients undergoing coronary angiogram at the study institution from October 2002 and January 2015 were assessed for a diagnosis of prominent Thebesian veins. A matched control group was created and comparisons between clinical, echocardiographic, and survival measures were made. Of 50,116 total patients, 31 (0.06%) were found to have prominent Thebesian veins on angiography and were compared with a matched control group of 596 patients. Patients were matched for age, gender, angiogram date, location and extent of coronary disease, and dominance. Demographic and clinical data were similar between cohorts, with a median follow-up period of 26 months. Patients with Thebesian veins had lower Doppler E wave (0.7 vs 0.8; p = 0.007) and A wave (0.6 vs 0.8; p = 0.001) mitral inflow velocities suggesting some decrease in normal mitral inflow, potentially due to direct shunting into the ventricle from the Thebesian vein network. However, there was no observed difference in left ventricular size or ejection fraction between groups. There was also no significantly increased mortality associated with the presence of Thebesian veins (hazard ratio 1.11, 95% CI 0.58 to 2.13). In conclusion, although previous reports have suggested adverse outcomes from Thebesian veins, our case-control study demonstrated no significant associated adverse cardiac structural changes or increase in mortality, although patients with Thebesian veins were noted to have a decrease in mitral inflow velocities.

Temporal trends of single-photon emission computed tomography myocardial perfusion imaging in patients without prior coronary artery disease: A 22-year experience at a tertiary academic medical center.

BACKGROUND: Between 1990 and 2006, there was a large national increase in utilization of single-photon emission computed tomography myocardial perfusion imaging (SPECT) for assessment of coronary artery disease (CAD). We aim to examine the trends of SPECT test results and patients' characteristics at Mayo Clinic Rochester. METHODS: Using the Mayo Clinic nuclear cardiology database, we examined all SPECT tests performed between January 1, 1991, and December 31, 2012, in patients without prior CAD. The study cohort was divided into 5 time periods: 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2012. RESULTS: There were 35,894 eligible SPECT tests (mean age 62.5 ± 12 years, 54% men). Annual utilization of SPECT increased significantly in 1992-2002 but then decreased without evidence of test substitution with stress echocardiography. There were modest changes in CAD risk factors over time. Testing of asymptomatic patients doubled (21.9% in 1991-1995 to 40% in 2006-2010) but later decreased to 33.6% in 2011-2012. Tests on patients with typical angina decreased dramatically (18.3% in 1991-1995 to 6.7% in 2011-2012). Summed stress score, summed difference score, and high-risk SPECT tests all decreased over time in both symptomatic and asymptomatic patients regardless of stress modality (exercise vs pharmacologic). CONCLUSIONS: In Mayo Clinic Rochester, annual SPECT utilization in patients without prior CAD increased in 1992-2002 but then decreased. Despite similar CAD risk factors and decreased utilization after 2003, more tests were low risk; summed stress score, summed difference score, and high-risk tests all decreased. Our findings confirm previous observations that SPECT was increasingly used in patients with a lower prevalence of CAD.

Relation between fractional flow reserve value of coronary lesions with deferred revascularization and cardiovascular outcomes in non-diabetic and diabetic patients.

BACKGROUND: FFR of deferred PCI lesions can predict future cardiovascular events. However, the prognostic utility of FFR remains unclear in diabetic patients in view of the potential impact of the diffuse nature of vascular disease process. We aimed to study the relation between fractional flow reserve (FFR) values and long-term outcomes of diabetic and non-diabetic patients with deferred percutaneous coronary intervention (PCI). METHODS: Patients with FFR assessment and deferred PCI (n=630) were enrolled and stratified according to diabetes mellitus (DM) status and FFR values. Patients were followed over a median of 39months. Cox proportional hazard regression models were used to analyze the association between clinical endpoints and clinical factors such as DM and FFR. RESULTS: In non-diabetics (n=450), higher FFR values were associated with less cardiovascular events (hazard ratio (HR) for death and myocardial infarction (MI) [95% confidence interval (CI)], 0.61[0.44 to 0.86] per 0.1 increase in FFR, p=0.007; HR for revascularization [95%CI], 0.66[0.49 to 0.9] per 0.1 increase in FFR, p=0.006). In diabetics (n=180), there was no difference in death and MI across the range of FFR values. Among those patients with an FFR >0.85, diabetics had a more than two-fold higher risk of death and MI than non-diabetics (HR [95% CI], 2.20 [1.19 to 4.01], p=0.015). CONCLUSION: Among non-diabetic patients with deferred PCI, a higher FFR was associated with lower rates of death, MI and revascularization. On the contrary in diabetic patients with deferred revascularization, FFR was not able to differentiate the risk of cardiovascular events.

Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis.

OBJECTIVE: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS). METHODS: We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test). RESULTS: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse. CONCLUSIONS: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.

Is lipid lowering therapy an independent risk factor for venous thromboembolism? A population-based case-control study.

INTRODUCTION: The independent effect of lipid lowering therapy (LLT) on venous thromboembolism (VTE) risk is uncertain. OBJECTIVE: To test statin and non-statin LLT as potential VTE risk factors. METHODS: Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively diagnosed incident VTE (cases) over the 13-year period, 1988-2000 (n=1340), and one to two matched controls (n=1538). We reviewed their complete medical records for baseline characteristics previously identified as independent VTE risk factors, and for statin and non-statin LLT. Using conditional logistic regression, we tested the overall effect of LLT on VTE risk and also separately explored the role of statin versus that of non-statin LLT, adjusting for other baseline characteristics. RESULTS: Among cases and controls, 74 and 111 received statin LLT, and 32 and 50 received non-statin LLT, respectively. Univariately, and after individually controlling for other potential VTE risk factors (i.e., BMI, trauma/fracture, leg paresis, hospitalization for surgery or medical illness, nursing home residence, active cancer, central venous catheter, varicose veins, prior superficial vein thrombosis, diabetes, congestive heart failure, angina/myocardial infarction, stroke, peripheral vascular disease, smoking, anticoagulation), LLT was associated with decreased odds of VTE (unadjusted OR=0.73; p=0.03). When considered separately, statin and non-statin LLT were each associated with moderate, non-significant lower odds of VTE. After adjusting for angina/myocardial infarction, each was significantly associated with decreased odds of VTE (OR=0.63, p<0.01 and OR=0.61, p=0.04, respectively). CONCLUSIONS: LLT is associated with decreased VTE risk after adjusting for known risk factors.

Relapses and disability accumulation in progressive multiple sclerosis.

OBJECTIVE: We examined the effect of relapses-before and after progression onset-on the rate of postprogression disability accrual in a progressive multiple sclerosis (MS) cohort. METHODS: We studied patients with primary progressive MS (n = 322) and bout-onset progressive MS (BOPMS) including single-attack progressive MS (n = 112) and secondary progressive MS (n = 421). The effect of relapses on time to Expanded Disability Status Scale (EDSS) score of 6 was studied using multivariate Cox regression analysis (sex, age at progression, and immunomodulation modeled as covariates). Kaplan-Meier analysis was performed using EDSS 6 as endpoint. RESULTS: Preprogression relapses (hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.34-1.98), postprogression relapses (HR: 1.37; 95% CI: 1.11-1.70), female sex (HR: 1.19; 95% CI: 1.00-1.43), and progression onset after age 50 years (HR: 1.47; 95% CI: 1.21-1.78) were associated with shorter time to EDSS 6. Postprogression relapses occurred in 29.5% of secondary progressive MS, 10.7% of single-attack progressive MS, and 3.1% of primary progressive MS. Most occurred within 5 years (91.6%) after progressive disease onset and/or before age 55 (95.2%). Immunomodulation after onset of progressive disease course (HR: 0.64; 95% CI: 0.52-0.78) seemingly lengthened time to EDSS 6 (for BOPMS with ongoing relapses) when analyzed as a dichotomous variable, but not as a time-dependent variable. CONCLUSIONS: Pre- and postprogression relapses accelerate time to severe disability in progressive MS. Continuing immunomodulation for 5 years after the onset of progressive disease or until 55 years of age may be reasonable to consider in patients with BOPMS who have ongoing relapses.

Population-based study of the use of cardiac stress imaging and referral for coronary angiography and repeated revascularization after coronary artery bypass graft surgery.

OBJECTIVE: To assess stress single-photon emission computed tomography (SPECT) and stress echocardiography use after coronary artery bypass grafting (CABG) and their effect on referral for coronary angiography and revascularization. PATIENTS AND METHODS: The referral, timing, and results of stress imaging after CABG; referral for coronary angiography and revascularization; and all-cause mortality were assessed in this longitudinal, population-based, retrospective study of 1138 Olmsted County, Minnesota, patients undergoing CABG between January 1, 1993, and December 31, 2003. RESULTS: A total of 570 patients (50.1%) underwent a stress imaging study (341 SPECT and 229 echocardiography) during the study period. Of the 1138 patients, 372 (32.7%) were referred for coronary angiography, and 144 of those patients (12.7%) underwent repeated revascularization (132 percutaneous revascularization and 12 CABG). The median interval between CABG and the index stress imaging study was 3.0 years (25th-75th percentile, 1.2-5.7 years). The results of 75.7% (258 of 341) of the stress SPECT studies and 70.7% (162 of 229) of the stress echocardiograms were abnormal. Seventy-six of 570 patients (13.3%) referred for stress imaging underwent coronary angiography within 180 days after the stress test. Repeated coronary revascularization was performed in 25 patients (4.4%) who underwent a stress imaging study within the preceding 180 days. The 5- and 10-year survival rates in the entire study cohort (83.5% and 65.1%, respectively) were not significantly different than predicted for the age- and sex-matched Minnesota population. CONCLUSION: Half of this community-based population of patients with CABG underwent stress SPECT or echocardiography during median follow-up of 8.9 years. Despite that approximately 75% of the results of stress imaging studies were abnormal, subsequent referral for coronary angiography within 180 days was low (13.3%), and the yield for repeated revascularization was very low (4.4%).

Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis.

BACKGROUND: It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases. OBJECTIVE: Our aim is to confirm that onset of progressive disease course is more relevant to the patient's age than the presence or duration of a pre-progression relapsing disease course in MS. METHODS: We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics (chi(2) or t-test), age-of-progression-onset (t-test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan-Meier analyses). RESULTS: Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. CONCLUSIONS: Patients with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

Hiatal Hernia Is Associated With an Increased Prevalence of Atrial Fibrillation in Young Patients.

Purpose: Hiatal hernia (HH) causes protrusion of the stomach into the chest cavity, directly impinging on the left atrium and possibly increasing predisposition to atrial arrhythmogenesis. However, such association has not been fully explored. The objective was to determine if an association between HH and atrial fibrillation (AF) exists and whether there are age- and sex-related differences. Methods: Adult patients diagnosed with HH from 1976 to 2006 at Mayo Clinic Rochester, Minnesota, were evaluated for AF. The number of patients with AF and HH was compared to age- and sex-matched patients with AF reported in the general population. Long-term outcomes were compared to corresponding county and state populations. Results: During the 30-year period, 111,429 patients were diagnosed with HH (mean age 61.4 ± 13.8 years, 47.9% male) and 7,865 patients (7.1%) also had a diagnosis of AF (mean age 73.1 ± 10.5 years; 55% male). In younger patients (<55 years), the occurrence of AF was 17.5-fold higher in men with HH and 19-fold higher in women with HH compared to the frequency of AF reported in the general population. Incidence of heart failure for patients with AF and HH was worse compared to the overall county population, but better than for those with AF. Similarly, mortality was worse in patients with AF and HH compared to the overall state population, but better than for those with AF in the county. Conclusion: Hiatal hernia appears to be associated with increased frequency of AF in both men and women of all age groups, but particularly in young patients. Further studies are needed to investigate this possible association and underlying mechanism.

Development and validation of a risk score to predict early mortality in recipients of implantable cardioverter-defibrillators.

BACKGROUND: Current guidelines do not recommend implantable cardioverter-defibrillator (ICD) implantation in patients with a life expectancy of <1 year. Better methods are needed for identifying patients at high risk for early mortality despite ICD therapy. OBJECTIVE: To develop and validate a risk prediction score to identify patients at high risk for death within 1 year despite ICD therapy. DESIGN: Detailed clinical data were collected on a large observational cohort of ICD patients from 3 tertiary care centers. One-third of the patients were randomly selected to form the prediction group (PG) from which a risk score was developed using logistic regression. This score was then applied to the remaining two-thirds of the cohort (validation group [VG]) to assess the risk score's predictive accuracy. RESULTS: The total cohort included 2717 ICD patients (mean age = 64.6 ± 14.5, male = 77.2%, primary prevention = 74.7%). A simple risk score incorporating peripheral arterial disease, age ≥ 70 years, creatinine ≥ 2.0 mg/dL, and ejection fraction ≤20% (PACE) accurately predicted 1-year mortality in the VG. Patients with a risk score of ≥3 had a >4-fold excess 1-year mortality compared with patients with a risk score of <3 (16.5% vs 3.5%; P <.0001). LIMITATION: Risk reduction provided by ICD therapy in this cohort is not known given the lack of a control group. CONCLUSIONS: A simple risk score accurately predicts 1-year mortality in ICD patients, as patients with a PACE risk score of ≥3 are at high risk despite ICD therapy.

The association of active cancer with venous thromboembolism location: a population-based study.

OBJECTIVE: To test active cancer for an association with venous thromboembolism (VTE) location. PATIENTS AND METHODS: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN, residents with incident VTE during the 35-year period 1966-2000 (N = 3385). We restricted analyses to residents with objectively diagnosed VTE during the 17-year period from January 1, 1984, to December 31, 2000 (N = 1599). For each patient, we reviewed the complete medical records in the community for patient age, gender, and most recent body mass index at VTE onset; VTE event type and location; and previously identified independent VTE risk factors (ie, surgery, hospitalization for acute medical illness, active cancer, leg paresis, superficial venous thrombosis, and varicose veins). Using logistic regression we tested active cancer for an association with each of 4 symptomatic VTE locations (arm or intra-abdominal deep venous thrombosis [DVT], intra-abdominal DVT, pulmonary embolism, and bilateral leg DVT), adjusted for age, gender, body mass index, and other VTE risk factors. RESULTS: In multivariate analyses, active cancer was independently associated with arm or intra-abdominal DVT (odds ratio [OR], 1.76; P = .01), intra-abdominal DVT (OR, 2.22; P = .004), and bilateral leg DVT (OR, 2.09; P = .02), but not pulmonary embolism (OR, 0.93). CONCLUSION: Active cancer is associated with VTE location. Location of VTE may be useful in decision making regarding cancer screening.