Stabilization of Rapidly Progressive Cardiac Allograft Vasculopathy Using mTOR Inhibition After Heart Transplantation.

BACKGROUND: Inhibition of the mammalian target of rapamycin (mTor) pathway after heart transplantation has been associated with reduced progression of coronary allograft vasculopathy (CAV). The application of low-dose mTOR inhibition in the setting of modern immunosuppression, including tacrolimus, remains an area of limited exploration. METHODS: This retrospective study included patients who received heart transplantation between January 2009 and January 2019 and had baseline, 1-year and 2-3-year coronary angiography with intravascular ultrasound (IVUS). Intimal thickness in 5 segments along the left anterior descending artery was compared across imaging time points in patients who were transitioned to low-dose mTOR inhibitor (sirolimus) vs standard treatment with mycophenolate on a background of tacrolimus. Long-term adverse cardiovascular outcomes (revascularization, severe CAV, retransplant, and cardiovascular death) were also assessed. RESULTS: Among 216 patients (mean age 51.5 ± 11.9 years, 77.8% men, 80.1% white), 81 individuals (37.5%) were switched to mTOR inhibition. mTOR inhibition was associated with a reduction in intimal thickness by 0.05 mm (95% CI 0.02-0.07; P < 0.001). This reduction was driven by patients who met the criteria for rapidly progressive CAV 1-year post-transplant (0.12 mm; P = 0.016 for interaction). After a median follow-up of 8.6 (IQR 6.6-11) years, 40 patients had major adverse cardiovascular outcomes. The use of mTOR inhibitors was not significantly associated with cardiovascular outcomes (P = 0.669). CONCLUSION: Transitioning patients after heart transplantation to an immunosuppression regimen composed of low-dose mTOR inhibition and tacrolimus was associated with a lack of progression of CAV, particularly in those with rapidly progressive CAV at 1 year, but not with long-term cardiovascular outcomes.

PCSK9 Inhibitors in Heart Transplant Patients: Safety, Efficacy, and Angiographic Correlates.

BACKGROUND: Statins are recommended in heart transplant patients, but are sometimes poorly tolerated. Alternative agents are often considered including proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i). We sought to investigate the use of PCSK9i after heart transplantation. METHODS AND RESULTS: We identified patients who received a heart transplant from 1999 to 2019 and were started on PCSK9i at our institution. Clinical, laboratory, and coronary angiography with intravascular ultrasound results were compared. Among 65 patients initiated on PCSK9i (48 for statin intolerance and 17 for refractory hyperlipidemia), the median time from transplant was 5.5 years (interquartile range [IQR], 2.8-9.9 years) with a median PCSK9 treatment duration of 1.6 years (IQR, 0.8-3.2 years) and 80% still on treatment. Evolocumab was used in 73.8%, alirocumab in 12.3%, and both in 13.8% owing to insurance coverage. All patients required prior authorization; initial denial occurred in 18.5% and 32.3% had denials in subsequent years. The median low-density lipoprotein cholesterol decreased from 130 mg/dL (IQR, 102-148 mg/dL) to 55 mg/dL (IQR, 35-74 mg/dL) after starting PCSK9i (P < .001), with 72% of patients achieving a low-density lipoprotein cholesterol of <70 mg/dL after treatment. There were also significant reductions of total cholesterol, non-high-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, and triglycerides, with a modest increase in high-density lipoprotein cholesterol. These changes were durable at latest follow-up. In 33 patients with serial coronary angiography and intravascular ultrasound, PCSK9i were associated with stable coronary plaque thickness and lumen area. CONCLUSIONS: Among heart transplant recipients, PCSK9i are effective in lowering cholesterol levels and stabilizing coronary intimal hyperplasia with minimal side effects. Despite favorable effects, access and affordability remain a challenge.

Influence of Donor Transmitted and Rapidly Progressive Coronary Vascular Disease on Long-Term Outcomes After Heart Transplantation: A Contemporary Intravascular Ultrasound Analysis.

BACKGROUND: Donor-transmitted atherosclerosis (DTA) and rapidly progressive cardiac allograft vasculopathy (CAV) at 1 year are intravascular ultrasound (IVUS)-derived measures shown to predict adverse cardiovascular outcomes in the setting of early generation immunosuppressive agents. Given the paucity of data on the prognostic value of IVUS-derived measurements in the current era, we sought to explore their association with adverse outcomes after heart transplantation. METHODS AND RESULTS: This is a retrospective cohort analysis of patients who underwent heart transplantation at our center between January 2009 and June 2016 with baseline and 1-year IVUS. Five IVUS sections were prospectively analyzed for intimal thickness and lumen area. DTA was defined as maximum intimal thickness of 0.5 mm or greater at baseline, and rapidly progressive CAV as an increase in maximum intimal thickness by 0.5 mm or more at 1 year. Our primary analysis assessed the relationship of IVUS and other clinical data on a composite outcome: coronary intervention, CAV stage 2 or 3 (defined by the International Society for Heart and Lung Transplantation 2010 nomenclature), or cardiovascular death. Among 249 patients (mean age 51.0 ± 12.2 years and 74.3% male) included in the analysis, DTA was detected in 118 patients (51.4%). Over a median follow-up of 6.1 years (interquartile range 4.2-8.0 years), 45 patients met the primary end point (23 percutaneous coronary intervention, 11 CAV 2 or 3, and 11 cardiovascular deaths as first event). DTA and rapidly progressive CAV were not associated with the primary end point, all-cause mortality, or retransplantation. In an additional analysis including post-transplant events, incident rejection was strongly associated with poor outcomes, although cytomegalovirus infection was not. CONCLUSIONS: In this contemporary cohort, IVUS-derived DTA and rapidly progressive CAV were not associated with medium- to long-term adverse events after heart transplantation.

Single-center utilization of donor-derived cell-free DNA testing in the management of heart transplant patients.

BACKGROUND: Gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) are useful in acute rejection (AR) surveillance in orthotopic heart transplant (OHT) patients. We report a single-center experience of combined GEP and dd-cfDNA testing for AR surveillance. METHODS: GEP and dd-cfDNA are tested together starting at 2 months post-OHT. After 6 months, combined testing was obtained before scheduled endomyocardial biopsy (EMB), and EMB was canceled with a negative dd-cfDNA. This approach was compared to using a GEP-only approach, where EMB was canceled with a negative GEP. We evaluated for frequency of EMB cancellation with dd-cfDNA usage. RESULTS: A total of 153 OHT patients over a 13-month period underwent 495 combined GEP/dd-cfDNA tests. 82.2% of dd-cfDNA tests were below threshold. Above threshold results identified high-risk patients who developed AR. 378 combined tests ≥6 months post-OHT resulted in cancellation of 83.9% EMBs as opposed to 71.2% with GEP surveillance alone. There were 2 acute cellular and 2 antibody-mediated rejection episodes, and no significant AR ≥6 months. CONCLUSION: Routine dd-cfDNA testing alongside GEP testing yielded a significant reduction in EMB volume by re-classifying GEP (+) patients into a lower risk group, without reduction in AR detection. The addition of dd-cfDNA identified patients at higher risk for AR.

Seated Pulmonary Artery Pressure Monitoring in Patients With Heart Failure: Results of the PROACTIVE-HF Trial.

BACKGROUND: Monitoring supine pulmonary artery pressures to guide heart failure (HF) management has reduced HF hospitalizations in select patients. OBJECTIVES: The purpose of this study was to evaluate the effect of managing seated mean pulmonary artery pressure (mPAP) with the Cordella Pulmonary Artery sensor on outcomes in patients with HF. METHODS: Following GUIDE-HF (Hemodynamic-GUIDEd Management of Heart Failure Trial), with U.S. Food and Drug Administration input, PROACTIVE-HF (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial) was changed from a randomized to a single-arm, open label trial, conducted at 75 centers in the USA and Europe. Eligible patients had chronic HF with NYHA functional class III symptoms, irrespective of the ejection fraction, and recent HF hospitalization and/or elevated natriuretic peptides. The primary effectiveness endpoint at 6 months required the HF hospitalization or all-cause mortality rate to be lower than a performance goal of 0.43 events/patient, established from previous hemodynamic monitoring trials. Primary safety endpoints at 6 months were freedom from device- or system-related complications or pressure sensor failure. RESULTS: Between February 7, 2020, and March 31, 2023, 456 patients were successfully implanted in modified intent-to-treat cohort. The 6-month event rate was 0.15 (95% CI: 0.12-0.20) which was significantly lower than performance goal (0.15 vs 0.43; P < 0.0001). Freedom from device- or system-related complications was 99.2% and freedom from sensor failure was 99.8% through 6 months. CONCLUSIONS: Remote management of seated mPAP is safe and results in a low rate of HF hospitalizations and mortality. These results support the use of seated mPAP monitoring and extend the growing body of evidence that pulmonary artery pressure-guided management improves outcomes in heart failure. (Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial [PROACTIVE-HF]; NCT04089059).

Effect of Dapagliflozin on 6-Minute Walk Distance in Heart Failure With Preserved Ejection Fraction: PRESERVED-HF.

BACKGROUND: Heart failure with preserved ejection fraction is associated with significant functional limitations, yet treatments for improving exercise performance have been elusive. We sought to explore the association between prespecified patient characteristics and changes in 6-minute walk distance that constitute a clinically significant response to dapagliflozin. METHODS: We performed a responder analysis to understand patient characteristics associated with clinically meaningful improvement in 6-minute walk test (6MWT) distance ≥15 m among patients randomized to 12 weeks of dapagliflozin versus placebo in the double-blind PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure). RESULTS: A total of 289 randomized patients had 6MWT distance completed at baseline and 12 weeks. Patients randomized to dapagliflozin improved walking distance by ≥15 m more frequently than those on placebo (n=64, 44% versus n=48, 34%). After adjusting for baseline covariates, patients randomized to dapagliflozin were more likely to experience a clinically meaningful improvement in 6MWT distance compared with those that received placebo (adjusted odds ratio, 1.66 [95% CI, 1.00-2.75]; P=0.05). Dapagliflozin-treated patients were also less likely to have a ≥15 m reduction in 6MWT distance compared with placebo-treated patients (adjusted odds ratio, 0.56 [95% CI, 0.33-0.94]; P=0.03). These results were consistent across all prespecified subgroups (all P values for interaction were not significant). CONCLUSIONS: Compared with those on placebo, patients with heart failure with preserved ejection fraction randomized to dapagliflozin were more likely to experience a clinically meaningful improvement and less likely to experience a deterioration in physical function over 12 weeks as measured by 6MWT distance. Beneficial response to dapagliflozin was consistent across prespecified subgroups. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030235.

Dapagliflozin Improves Heart Failure Symptoms and Physical Limitations Across the Full Range of Ejection Fraction: Pooled Patient-Level Analysis From DEFINE-HF and PRESERVED-HF Trials.

BACKGROUND: Patients with heart failure (HF) have a high burden of symptoms and physical limitations, regardless of ejection fraction (EF). Whether the benefits of SGLT2 (sodium-glucose cotransporter-2) inhibitors on these outcomes vary across the full range of EF remains unclear. METHODS: Patient-level data were pooled from the DEFINE-HF trial (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction) of 263 participants with reduced EF (≤40%), and PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure) of 324 participants with preserved EF (≥45%). Both were randomized, double-blind 12-week trials of dapagliflozin versus placebo, recruiting participants with New York Heart Association class II or higher and elevated natriuretic peptides. The effect of dapagliflozin on the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at 12 weeks was tested with ANCOVA adjusted for sex, baseline KCCQ, EF, atrial fibrillation, estimated glomerular filtration rate, and type 2 diabetes. Interaction of dapagliflozin effects on KCCQ-CSS by EF was assessed using EF both categorically and continuously with restricted cubic spline. Responder analyses, examining proportions of patients with deterioration, and clinically meaningful improvements in KCCQ-CSS were conducted using logistic regression. RESULTS: Of 587 patients randomized (293 dapagliflozin, 294 placebo), EF was ≤40, >40-≤60, and >60% in 262 (45%), 199 (34%), and 126 (21%), respectively. Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference 5.0 points [95% CI, 2.6-7.5]; P<0.001). This was consistent in participants with EF≤40 (4.6 points [95% CI, 1.0-8.1]; P=0.01), >40 to ≤60 (4.9 points [95% CI, 0.8-9.0]; P=0.02) and >60% (6.8 points [95% CI, 1.5-12.1]; P=0.01; Pinteraction=0.79). Benefits of dapagliflozin on KCCQ-CSS were also consistent when analyzing EF continuously (Pinteraction=0.94). In responder analyses, fewer dapagliflozin-treated patients had deterioration and more had small, moderate, and large KCCQ-CSS improvements versus placebo; these results were also consistent regardless of EF (all Pinteractionvalues nonsignificant). CONCLUSIONS: In patients with HF, dapagliflozin significantly improves symptoms and physical limitations after 12 weeks of treatment, with consistent and clinically meaningful benefits across the full range of EF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT02653482 and NCT03030235.

Clinical factors associated with left ventricular ejection fraction disparity in patients with left ventricular dysfunction undergoing multimodality imaging.

Drug and device therapy for heart failure is increasingly determined based on left ventricular ejection fraction. Significant disparity frequently exists between echocardiographic and nuclear scintigraphic techniques, even when testing is performed nearly simultaneously in clinically stable patients. In 119 patients with left ventricular dysfunction who underwent both echocardiography and stress testing with nuclear imaging within seven days (but with significant disparity in reported left ventricular ejection fraction), we identified four clinical variables which were associated with left ventricular ejection fraction difference. These clinical variables included atrial fibrillation, left ventricular hypertrophy, severe mitral regurgitation and paced rhythm.

Effects of GLP-1 receptor agonists and SGLT-2 inhibitors in heart transplant patients with type 2 diabetes: Initial report from a cardiometabolic center of excellence.

Type 2 diabetes mellitus (T2D) is a common comorbidity among patients who have undergone heart transplantation. Recently two classes of glucose-lowering medications (sodium-glucose cotransporter type-2 inhibitors [SGLT-2Is] and glucagon-like-peptide-1 receptor agonists [GLP-1RAs]), have been shown to significantly improve cardiovascular outcomes. There is a paucity of data regarding their use in immunosuppressed patients, with many studies specifically excluding this population. We retrospectively evaluated the safety and efficacy of GLP-1RAs and SGLT-2Is in patients who had undergone orthotopic heart transplant at a high-volume center. Among 21 patients, we found significant weight loss, reductions in insulin use, hemoglobin A1c, and low-density lipoprotein-cholesterol. Moreover, both SGLT-2Is and GLP-1RAs were well tolerated with no adverse events leading to discontinuation of either therapy. While larger studies of patients after solid organ transplant are needed, this small hypothesis-generating study demonstrates that SGLT-2Is and GLP-1RAs appear safe and effective therapies among patients with T2D after heart transplant.

Comparison of Outcomes Among Patients With Cardiogenic Shock Admitted on Weekends Versus Weekdays.

Cardiogenic shock (CS) is associated with high mortality and often requires involvement of a multidisciplinary provider team to deliver timely care. Care coordination is more difficult on weekends, which may lead to a delay in care. We sought to assess the effect of weekend admissions on outcomes in patients admitted with CS. Patients admitted with CS were identified from 2005 to 2014 in the National Inpatient Sample using ICD9 code 785.51. Baseline demographics, in-hospital procedures, and outcomes were obtained and compared by day of admission. A multivariable model was used to assess the impact of weekend admission on in-hospital mortality. A total of 875,054 CS admissions were identified (age 67.4 ± 15.1 years, 40.2% female, 72.1% Caucasian), with 23% of patients being admitted on weekends. Baseline co-morbidities were similar between groups. Weekend admissions were associated with higher in-hospital mortality (40.6% vs 37.5%) and cardiac arrest (20.3% vs 18.1%, p < 0.001 for both) consistently over the study period. Use of temporary and permanent mechanical support devices and heart transplantation were slightly less common for weekend admissions. In a multivariable model adjusting for relevant confounders, weekend admission was associated with a 10% increased mortality in patients with CS. In conclusion, patients with CS admitted on weekends had higher in-hospital mortality and were slightly less likely to receive mechanical support and advanced therapies compared with those admitted on weekdays. Future studies and health system initiatives should focus on rectifying these disparities with around-the-clock multidisciplinary coordinated care for CS.

The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

Characterization and timing of gastrointestinal bleeding in continuous flow left ventricular assist device recipients.

BACKGROUND AND AIMS: Heart failure is one of the leading causes of morbidity and mortality in the United States. The advent of left ventricular assist devices (LVAD) has improved the survival and quality of life in patients with end stage heart failure. Gastrointestinal bleeding (GIb) remains one of the limitations of LVADs. METHODS: A single center, retrospective review of records was performed for patients who underwent LVAD implantation between 2010 and 2015. All patients who survived more than 30 days were followed till March 2016 and are described below. RESULTS: A total of 79 patients were included in the study. The rate of GIb was 34.1% (27 patients) with a mean time to bleed of 267 days. Older patients were more likely to bleed. Upper GI bleeding was the source of bleeding in 54% patients. Arteriovenous malformations (AVM) were the source of bleeding in 74% bleeders and 80% of these patients had de novo AVM formation. 14/27 (51%) patients had a re-bleeding event. Thrombotic events were 4.5 times more likely to occur in patients who also had a GI bleed. CONCLUSIONS: GI bleeding in LVAD patients is common with the source of bleeding more commonly being in the upper GI tract. GI bleeding may occur as early as 10 days post procedure, despite previous negative screening endoscopies. There is an increased risk of thrombotic events in patients who have experienced a GI bleed.

Combined assessment of myocardial perfusion and diastolic function enhances risk stratification in patients with anterior wall myocardial infarction.

OBJECTIVE: Evaluate the utility of a combined risk stratification scheme including diastolic dysfunction and "no-reflow," to identify high-risk patients following acute myocardial infarction (AMI). BACKGROUND: Recent studies have demonstrated that the "no-reflow" phenomenon (defined by myocardial contrast echocardiography) and severe diastolic dysfunction (identified by Doppler echocardiography) identify patients at high risk for mortality following AMI. METHODS: We evaluated 111 patients with recent anterior acute myocardial infarction from July 2000 to June 2004. Diastolic function and myocardial perfusion was evaluated by echocardiography. Patients were placed into 1 of 3 groups based on diastolic function and myocardial perfusion: Group 1 (normal perfusion and normal diastolic function), Group 2 (abnormal perfusion or abnormal diastolic function), and Group 3 (abnormal perfusion and abnormal diastolic function). We compared the long term all-cause mortality within these groups. RESULTS: Patients in each group were similar with respect to myocardial infarction size as defined by biomarkers, extent and severity of coronary artery disease, and medical and interventional therapy. Mortality was much higher in Group 3 (26.9%) compared to Group 1 (0%) and Group 2 (15.2%) (p = 0.048). CONCLUSION: Combined assessment of diastolic function and myocardial perfusion enhances risk stratification post myocardial infarction.

Mortality rates and clinical predictors of reduced survival after cardioverter defibrillator implantation.

We aimed to identify mortality rates and clinical predictors of reduced survival in a large cohort of patients after implantation of an implantable cardioverter-defibrillator (ICD). Although existing data from clinical trials report annual mortality after ICD implantation from 2% to 9%, there are few data available on mortality rates or predictors of reduced survival in this patient population in clinical practice. In this single-center, retrospective analysis of 286 patients who underwent ICD implantation between June 1, 2000 and December 30, 2003, candidate predictors of mortality were assessed and subjected to multivariable analysis. Outcomes were documented using the Social Security Death Master File and hospital medical records. Overall annualized mortality was 11.3% after ICD implantation. Mortality rates in patients with left ventricular ejection fraction (LVEF) <25% were 27.2% at 1 year and 50.5% at 3 years. Digoxin (hazard ratio 1.86, 95% confidence interval [CI] 1.21 to 2.86, p = 0.0046) and loop diuretics (hazard ratio 1.59, 95% CI 1.06 to 2.38, p = 0.024) were associated with reduced survival. Angiotensin-converting enzyme inhibitor or aldosterone receptor blocker use was associated with reduced mortality (hazard ratio 0.50, 95% CI 0.31 to 0.80, p = 0.0038). In conclusion, mortality after ICD implantation is higher than demonstrated in primary or secondary prevention ICD trials; LVEF remains a potent predictor of mortality after ICD implantation, particularly in patients with an LVEF <25%; loop diuretic and digoxin use is associated with an approximate twofold increase in mortality in this population; and angiotensin-converting enzyme inhibitor or aldosterone receptor blocker use is associated with improved survival after ICD implantation.

Transesophageal echocardiographic diagnosis of left atrial appendage occluder device infection.

The safety and efficacy of a left atrial appendage closure device is currently under evaluation in a large-scale multi-center clinical trial. We report an initial case of left atrial appendage occluder device infection with Staphylococcus aureus; transesophageal echocardiography played a pivotal role in diagnosis and treatment.

Clinical and echocardiographic markers of mortality risk in patients with atrial fibrillation.

Atrial fibrillation (AF) is independently associated with increases in cardiovascular and all-cause mortality. Although cardiovascular co-morbidities predict stroke risk in AF, their relation with mortality has not been well described. To identify clinical and echocardiographic markers of mortality in patients with AF, 524 patients with AF underwent transesophageal echocardiography from August 2000 to March 2005. Clinical risk factors for systemic thromboembolism were determined for each patient. A CHADS2 (congestive heart failure, hypertension, age>75 years, diabetes, and previous stroke or transient ischemic attack) score ranging from 0 to 6 was calculated for each patient. Transesophageal echocardiographic reports were reviewed for the presence of left atrial spontaneous echocardiographic contrast, left atrial thrombus, the left ventricular ejection fraction, aortic arch atheroma, and the presence and severity of mitral regurgitation. Mortality data were obtained from the Social Security Death Master File. Univariate and multivariate models were structured to assess which variables predicted mortality. In a multivariate model, a history of heart failure, age>75 years, the absence of systemic anticoagulation with warfarin, the presence of left atrial spontaneous echocardiographic contrast, and greater than moderate mitral regurgitation were independent predictors of mortality. Increasing CHADS2 score was also an independent predictor of mortality. A CHADS2 score of 5 or 6 was associated with a >50-fold increase in mortality compared with patients with CHADS2 scores of 0. In conclusion, a history of heart failure, age>or=75 years, the absence of chronic oral anticoagulation, a CHADS2 score>0, and greater than moderate mitral regurgitation are independent predictors of mortality in patients with AF.

Usefulness of myocardial contrast echocardiography in predicting late mortality in patients with anterior wall acute myocardial infarction.

We investigated whether myocardial contrast echocardiography (MCE) performed soon after acute myocardial infarction (AMI) improves risk stratification for late mortality. MCE after AMI identifies microvascular "no-reflow" and predicts early outcomes; however, the predictive value of MCE for late mortality is unknown. One hundred sixty-seven patients with anterior AMI and left ventricular dysfunction underwent MCE 2 days after admission, and a perfusion score index (PSI) was calculated. Long-term follow-up (mean 39 months) was available for all patients. Patients with normal and abnormal perfusion had similar baseline characteristics. Myocardial contrast echocardiographic PSI was a predictor of mortality as a continuous variable (odds ratio 3.2 for each 1.0 increase in PSI, 95% confidence interval 1.1 to 9.7, p = 0.04). In a logistic regression model, age (odds ratio 2.6 per decade, 95% confidence interval 1.6 to 4.4, p = 0.0002) and PSI (odds ratio 4.5 for each 1.0 increase in PSI, 95% confidence interval 1.3 to 15.4, p = 0.02) were the only significant predictors of mortality. In a subanalysis comparing patients >70 years old with abnormal PSI with all other patients, Kaplan-Meier estimates showed a marked difference in survival over a mean follow-up of 39 months (24% vs 4% mortality, p = 0.0002). In conclusion, MCE refines risk stratification soon after anterior AMI in patients with left ventricular dysfunction. Patients at very high and very low risk of mortality can be identified, and myocardial contrast echocardiographic data are incrementally useful compared with existing clinical and angiographic variables.

Contrast administration reduces interobserver variability in determination of left ventricular ejection fraction in patients with left ventricular dysfunction and good baseline endocardial border delineation.

Echocardiographic contrast agents improve endocardial border delineation in patients with technically difficult baseline studies. With medical and device therapy for heart failure increasingly based on left ventricular (LV) ejection fraction (EF) partition values, the accurate and reproducible assessment of LV function is necessary. It was hypothesized that routine contrast enhancement would significantly reduce interobserver variability in the determination of LVEFs in a cohort of patients with LV dysfunction and good baseline endocardial delineation. All patients underwent baseline noncontrast studies followed by contrast-enhanced imaging using Definity. Two experienced echocardiographers, blinded to the clinical data, determined LVEFs using 4 different techniques: noncontrast estimated (NCE), noncontrast calculated (NCC), contrast estimated (CE), and contrast calculated (CC). Using a mixed-model procedure that allows for fixed and random events, the variance due to error and that due to the patient was obtained (interclass correlation). The proportion of variation due to the reader was calculated as 1--interclass correlation. Mean standardized percentage differences ([reader 1 EF--reader 2 EF]/mean EF) were also calculated for each method. The proportion of variation due to the reader was smallest in the CC group and largest in the NCC group (NCE = 0.21, NCC = 0.33, CE = 0.25, CC = 0.11). The results were similar when only patients with NCE EFs >or=20% and or=20% and or=20% and