Adelaide M. Arruda-Olson

Prognostic Value of Exercise Echocardiography in 5,798 Patients: Is There a Gender Difference?

OBJECTIVES This study was designed to determine the effect of gender on the prognostic value of exercise echocardiography. BACKGROUND Limited information exists regarding gender differences in prognostic value of exercise echocardiography. METHODS We obtained follow-up (3.2 +/- 1.7 years) in 5,798 consecutive patients who underwent exercise echocardiography for evaluation of known or suspected coronary artery disease. RESULTS There were 3,322 men (mean age 62 +/- 12 years) and 2,476 women (mean age 62 +/- 12 years) (p = 0.7). New or worsening wall motion abnormalities developed with exercise in 35% of men and 25% of women (p = 0.001). Cardiac events, including cardiac death (107 patients) and nonfatal myocardial infarction (148 patients), occurred in 5.3% of men and 3.1% of women (p = 0.001). Addition of the percentage of ischemic segments to the clinical and rest echocardiographic model provided incremental information in predicting cardiac events for both men (chi(2) = 137 to 143, p = 0.014) and women (chi(2) = 72 to 76, p = 0.046). By multivariate analysis, exercise electrocardiographic and exercise echocardiographic predictors of cardiac events in both men and women were workload and exercise wall motion score index. There was no significant interaction effect of rest echocardiography (p = 0.79), exercise electrocardiography (p = 0.38) or exercise echocardiography (p = 0.67) with gender. CONCLUSIONS Although cardiac events occurred more frequently in men, the incremental value of exercise echocardiography was comparable in both genders. Of all exercise electrocardiographic and exercise echocardiographic variables, workload and exercise wall motion score index had the strongest association with outcome. The results of exercise echocardiography have comparable implications in both men and women.

Neutrophilia Predicts Death and Heart Failure After Myocardial Infarction A Community-Based Study

Background—The relationship between neutrophils and outcomes post–myocardial infarction (MI) is not completely characterized. We examined the associations of neutrophil count with mortality and post-MI heart failure (HF) and their incremental value for risk discrimination in the community. Methods and Results—MI was diagnosed with cardiac pain, biomarkers, and Minnesota coding of the ECG. Neutrophil count at presentation, reported as counts ×109/L, was categorized by tertiles (lower tertile, <5.7; middle tertile, 5.7 to 8.5; upper tertile, >8.5). From 1979 to 2002, 2047 incident MIs occurred in Olmsted County, Minn (mean age, 68±14 years; 44% women). Median (25th to 75th percentile) neutrophil count was 7.0 (5.1 to 9.5). Within 3 years post-MI, 577 patients died, and 770 developed HF. Overall survival and survival free of HF decreased with increased neutrophil tertile (P<0.001). Compared with the lower tertile, the age and sex adjusted hazard ratio for death was 1.44 (95% CI, 1.14 to 1.81) for the middle tertile and 2.60 (95% CI, 2.10 to 3.22) for the upper tertile (P<0.001). Similarly, for HF, the hazard ratio was 1.32 (95% CI, 1.09 to 1.59) for the middle and 2.12 (95% CI, 1.77 to 2.53) for the upper tertile (P<0.001). These associations persisted after adjustment for risk factors, comorbidities, Killip class, revascularization, and ejection fraction. Neutrophil count improved risk discrimination as indicated by increases in the area under the receiver operating characteristic curves (all P<0.05) and by the integrated discrimination improvement analysis (all P<0.001). Conclusions—In the community, the neutrophil count was strongly and independently associated with death and HF post-MI and improved risk discrimination over traditional predictors.

Billing code algorithms to identify cases of peripheral artery disease from administrative data

Objective To construct and validate billing code algorithms for identifying patients with peripheral arterial disease (PAD). Methods We extracted all encounters and line item details including PAD-related billing codes at Mayo Clinic Rochester, Minnesota, between July 1, 1997 and June 30, 2008; 22 712 patients evaluated in the vascular laboratory were divided into training and validation sets. Multiple logistic regression analysis was used to create an integer code score from the training dataset, and this was tested in the validation set. We applied a model-based code algorithm to patients evaluated in the vascular laboratory and compared this with a simpler algorithm (presence of at least one of the ICD-9 PAD codes 440.20–440.29). We also applied both algorithms to a community-based sample (n=4420), followed by a manual review. Results The logistic regression model performed well in both training and validation datasets (c statistic=0.91). In patients evaluated in the vascular laboratory, the model-based code algorithm provided better negative predictive value. The simpler algorithm was reasonably accurate for identification of PAD status, with lesser sensitivity and greater specificity. In the community-based sample, the sensitivity (38.7% vs 68.0%) of the simpler algorithm was much lower, whereas the specificity (92.0% vs 87.6%) was higher than the model-based algorithm. Conclusions A model-based billing code algorithm had reasonable accuracy in identifying PAD cases from the community, and in patients referred to the non-invasive vascular laboratory. The simpler algorithm had reasonable accuracy for identification of PAD in patients referred to the vascular laboratory but was significantly less sensitive in a community-based sample.

Troponin T levels and infarct size by SPECT myocardial perfusion imaging.

OBJECTIVES To evaluate the relationship between serial cardiac troponin T (cTnT) levels with infarct size and left ventricular ejection fraction by gated single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with acute myocardial infarction (AMI). BACKGROUND Current guidelines recommend the use of cTnT as the biomarker of choice for the diagnosis of AMI. Data relating cTnT to SPECT-MPI in patients with AMI are limited. METHODS A subset of patients with their first AMI participating in a community-based cohort of AMI in Olmsted County, Minnesota, were prospectively studied. Serial cTnT levels were evaluated at presentation, <12 h and 1, 2, and 3 days after onset of pain. Peak cTnT was defined as the maximum cTnT value. RESULTS A total of 121 patients (age, 61 ± 13 years; 31% women) with AMI underwent gated SPECT-MPI at a median (25th percentile, 75th percentile) of 10 (5, 15) days post-AMI. The type of infarct was non-ST-segment elevation myocardial infarction in 61%, and 13% were anterior in location. The median infarct size was 1% (0%, 11%) and the median gated left ventricular ejection fraction was 54% (47%, 60%). Fifty-nine patients (49% of the population) had no measurable infarction by SPECT-MPI. Independent predictors of measurable SPECT-MPI infarct size included cTnT at days 1, 2, and 3 and peak cTnT, but not at presentation or <12 h. In receiver-operator characteristic analysis, the area under the curve was highest at day 3. Receiver-operator characteristic analysis demonstrated a cutoff of 1.5 ng/ml for peak cTnT for the detection of measurable infarct size. CONCLUSIONS In a community-based cohort of patients with their first AMI, independent predictors of measurable SPECT-MPI infarct size included cTnT at days 1, 2, and 3 and peak cTnT. In contrast, cTnT level at presentation and <12 h was not an independent predictor of myocardial infarction size as assessed by SPECT-MPI. Receiver-operator characteristic analysis demonstrated a cutoff value peak cTnT of 1.5 ng/ml for the detection of measurable infarct.

Yield of noncardiac biopsy for the diagnosis of transthyretin cardiac amyloidosis

Transthyretin (ATTR) cardiac amyloidosis may be because of mutant transthyretin causing familial amyloid cardiomyopathy (FAC) or wild-type transthyretin causing systemic senile amyloidosis (SSA). Histologic confirmation is often challenging and may require endomyocardial biopsy (EMB). The purpose of this study was to determine the frequency of amyloid protein deposition in positive noncardiac organ biopsy or fat aspiration in patients with ATTR cardiac amyloidosis. The medical records of 286 patients (mean age 66 ± 11, 85% men) with a diagnosis of ATTR cardiac amyloidosis at our institution who underwent noncardiac biopsy or subcutaneous fat aspiration were reviewed, including 186 patients (65%) with FAC and 100 patients (35%) with SSA. One hundred and thirty-one patients (46%) had EMB, all of which were positive. There were 210 patients (73%) with positive noncardiac tissue sampling, including 175 patients (94%) with FAC and 35 patients (35%) with SSA (p <0.001). There were 141 patients (76%) with FAC and 84 patients (84%) with SSA who underwent fat aspiration, and 67% and 14% were positive, respectively, whereas 100 (54%) and 64 (64%) underwent bone marrow biopsy, and 41% and 30% were positive, respectively. Rectal and sural nerve biopsies were performed in 52 (28%) and 54 (29%) patients with FAC and were positive in 81% and 83%, respectively. Biopsy of other noncardiac sites was performed with relatively lower frequency. In conclusion, although EMB is more commonly required to establish the diagnosis of SSA than FAC, noncardiac biopsy or fat aspiration could be considered as initial testing in patients evaluated for ATTR cardiac amyloidosis with characteristic echocardiography findings.

Sleep Apnea and Cardiovascular Disease Implications for Understanding Erectile Dysfunction

Abstract.Background and Purpose: There is increasing recognition of the high and rising prevalence of obstructive sleep apnea (OSA). It has been suggested that OSA may contribute to erectile dysfunction. This review will examine the evidence and potential mechanisms, including abnormalities of neural, endothelial and hormonal function, linking OSA to erectile dysfunction. Conclusion: Available data suggest, but do not prove, a higher prevalence of erectile dysfunction in OSA. Certainly, the pathologic processes activated by OSA are also those that may predispose to impaired erectile function. Further well-designed and controlled studies are needed to show conclusively that any increased prevalence of erectile dysfunction in OSA is secondary to the OSA per se and not a consequence of the frequently associated comorbidities, such as obesity and vascular disease, that characterize this patient population.Zusammenfassung.Hintergrund und Ziel: Zunehmend wird die Bedeutung des Schlafapnoe-Syndroms für kardiovaskuläre Erkrankungen erkannt und eine hohe Prävalenz festgestellt. Es ist vermutet worden, dass das Schlafapnoe-Syndrom zur erektilen Dysfunktion beiträgt. Die Übersichtsarbeit soll die Gründe und die potentiellen Mechanismen aufdecken. Betrachtet werden Veränderungen der neuronalen, endothelialen und hormonellen Funktion, die zum Schlafapnoe-Syndrom in Beziehung stehen. Schlussfolgerung: Vorhandene Daten lassen vermuten, dass bei Schlafapnoe-Syndrom die erektile Dysfunktion häufiger vorkommt, ohne dass aber ein eindeutiger Beweis vorliegt. Die pathologischen Mechanismen, die ein Schlafapnoe-Syndrom auslösen, können auch zur erektilen Dysfunktion führen. Weitergehende kontrollierte Studien sind notwendig, um festzustellen, ob die erektile Dysfunktion Folge des Schlafapnoe-Syndroms ist. Auch die Prävalenz ist bei dem Syndrom erhöht. Möglicherweise ist aber die erektile Dysfunktion nur eine Folge der Komorbiditäten wie Übergewicht und kardiovaskuläre Erkrankungen, die bei diesem Patienten vorkommen.

Left Ventricular Function and C-Reactive Protein Levels in Acute Myocardial Infarction

To examine left ventricular (LV) function in patients after acute myocardial infarction (AMI) and assess its relation to C-reactive protein (CRP) as a measure of the early inflammatory response. We measured the CRP levels early after AMI and correlated them with the early structural and functional cardiac alterations. From November 2002 to December 2007, we prospectively enrolled community subjects who had experienced an AMI, as defined by standardized criteria, measured the CRP level, and obtained an echocardiogram. The study consisted of 514 patients (mean age 67 +/- 15 years, 59% men). CRP was measured early after symptom onset (median 6.1 hours; twenty-fifth to seventy-fifth percentile 2.2 to 11.1). The median CRP level was 4.8 mg/L (twenty-fifth to seventy-fifth percentile 1.8 to 24). The echocardiograms were obtained at a median of 1 day after AMI. The wall motion score index, LV ejection fraction, and LV diameter were similar across the CRP tertiles (all p >0.05). Greater CRP levels were associated with the presence of moderate or severe diastolic dysfunction (p = 0.002) and moderate or severe mitral regurgitation (p <0.001). The association with moderate or severe mitral regurgitation was independent of the clinical characteristics and ST-segment elevation status. In conclusion, at the initial phase of AMI, CRP elevation was associated with the presence and severity of mitral regurgitation and diastolic dysfunction. This suggests that inflammation is related to the ventricular remodeling processes, independently of LV systolic function.

A Perspective on the New American College of Cardiology/American Heart Association Guidelines for Cardiovascular Risk Assessment

The recently published American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for cardiovascular risk assessment provide equations to estimate the 10-year and lifetime atherosclerotic cardiovascular disease (ASCVD) risk in African Americans and non-Hispanic whites, include stroke as an adverse cardiovascular outcome, and emphasize shared decision making. The guidelines provide a valuable framework that can be adapted on the basis of clinical judgment and individual/institutional expertise. In this review, we provide a perspective on the new guidelines, highlighting what is new, what is controversial, and potential adaptations. We recommend obtaining family history of ASCVD at the time of estimating ASCVD risk and consideration of imaging to assess subclinical disease burden in patients at intermediate risk. In addition to the adjuncts for ASCVD risk estimation recommended in the guidelines, measures that may be useful in refining risk estimates include carotid ultrasonography, aortic pulse wave velocity, and serum lipoprotein(a) levels. Finally, we stress the need for research efforts to improve assessment of ASCVD risk given the suboptimal performance of available risk algorithms and suggest potential future directions in this regard.

Effect of Second-Generation Sulfonylureas on Survival in Patients With Diabetes Mellitus After Myocardial Infarction

OBJECTIVE To examine possible adverse effects of sulfonylureas on survival among patients with diabetes mellitus (DM) who experience a myocardial infarction (MI). PATIENTS AND METHODS Residents of Olmsted County, Minnesota, with an MI that met standardized criteria from January 1, 1985, through December 31, 2002, were followed up for mortality. RESULTS Among 2189 patients with MI (mean ± SD age, 68±14 years; 1237 men [57%]), 409 (19%) had DM. The 23 patients treated with first-generation sulfonylureas, biguanides, or thiazolidinediones were excluded from analyses. Among the remaining 386 patients with DM, 120 (31%) were taking second-generation sulfonylureas, 180 (47%) were taking insulin, and 86 (22%) were receiving nonpharmacological treatment. Patients with DM treated with second-generation sulfonylureas were more likely to be men and have higher creatinine clearance than those treated with insulin. After adjusting for age, sex, Killip class, duration of DM, creatinine clearance, and reperfusion therapy or revascularization, patients treated with second-generation sulfonylureas had a lower risk of death than did diabetic patients receiving insulin (hazard ratio, 0.41; 95% confidence interval, 0.21-0.80; P =.009). CONCLUSION These population-based data do not support the concern about an adverse effect of second-generation sulfonylureas on survival after MI and underscore the importance of population-based studies of surveillance of drug safety.

Genotype, echocardiography, and survival in familial transthyretin amyloidosis

Abstract Background: More than 100 transthyretin (TTR) variants have been identified which cause familial systemic amyloidosis. It has been increasingly recognized that TTR variants of familial systemic amyloidosis contribute to clinical characteristics, including age at diagnosis, cardiac phenotype and survival. Methods: Two hundred and eighty-two patients who underwent genotyping for TTR variants were identified. This study focused on 116 patients representing the three most common TTR variants; T60A (n = 58), V30M (n = 37) and V122I (n = 21). The remaining subjects (n = 61) were distributed amongst 33 different genotypes and excluded from analysis. Results: Age at diagnosis was similar by genotype. Septal, posterior wall thickness, right ventricular systolic pressure and left ventricular mass index were greater and LVEF lower in the V122I subgroup. At mean follow up of 3.0 ± 2.6 years there were 62 deaths. V30M patients had the best survival. Survival was similar between V122I and T60A patients. The association of genotype with mortality persisted after adjustments for clinical variables. Conclusions: For familial TTR amyloidosis cardiac involvement is frequent and mortality high for T60A, V122I and V30M genotypes. Specific genotype predicted severity of phenotypic expression as measured by echocardiography and survival.