Nutrition Intervention for Reduction of Cardiovascular Risk in African Americans Using the 2019 American College of Cardiology/American Heart Association Primary Prevention Guidelines.

INTRODUCTION: The 2019 American College of Cardiology/American Heart Association (ACC/AHA) Prevention Guidelines emphasize reduction in dietary sodium, cholesterol, refined carbohydrates, saturated fat and sweetened beverages. We hypothesized that implementing this dietary pattern could reduce cardiovascular risk in a cohort of volunteers in an urban African American (AA) community church, during a 5-week ACC/AHA-styled nutrition intervention, assessed by measuring risk markers and adherence, called HEART-LENS (Helping Everyone Assess Risk Today Lenten Nutrition Study). METHODS: The study population consisted of 53 volunteers who committed to eat only home-delivered non-dairy vegetarian meals (average daily calories 1155, sodium 1285 mg, cholesterol 0 mg; 58% carbohydrate, 17% protein, 25% fat). Body mass index (BMI) and fasting serum markers of cardiometabolic and risk factors were measured, with collection of any dietary deviation. RESULTS: Of 53 volunteers, 44 (mean age 60.2 years, 37 women) completed the trial (88%); 1 was intolerant of the meals, 1 completed both blood draws but did not eat delivered food, and 7 did not return for the tests. Adherence to the diet was reported at 93% in the remaining 44. Cardiometabolic risk factors improved significantly, highlighted by a marked reduction in serum insulin (-43%, p = 0.000), hemoglobin A1c (6.2% to 6.0%, p = 0.000), weight and BMI (-10.2 lbs, 33 to 31 kg/m2, p = 0.000), but with small reductions of fasting glucose (-6%, p = 0.405) and triglyceride levels (-4%, p = 0.408). Additionally, improved were trimethylamine-N-oxide (5.1 to 2.9 µmol/L, -43%, p = 0.001), small dense low-density lipoprotein cholesterol (LDL) (24.2 to 19.1 mg/dL, -21%, p = 0.000), LDL (121 to 104 mg/dL, -14%, p = 0.000), total cholesterol (TC) (190 to 168 mg/dL, -12%, p = 0.000), and lipoprotein (a) (LP(a)) (56 to 51 mg/dL, -11%, p = 0.000); high sensitivity C-reactive protein (hs-CRP) was widely variable but reduced by 16% (2.5 to 2.1 ng/mL, p = NS) in 40 subjects without inflammatory conditions. Soluble urokinase plasminogen activator (suPAR) levels were not significantly changed. The ACC/AHA pooled cohort atherosclerotic cardiovascular disease (ASCVD) risk scores were calculated for 41 and 36 volunteers, respectively, as the ASCVD risk could not be calculated for 3 subjects with low lipid fractions at baseline and 8 subjects after intervention (p = 0.184). In the remaining subjects, the mean 10-year risk was reduced from 10.8 to 8.7%, a 19.4% decrease (p = 0.006), primarily due to a 14% decrease in low-density lipoprotein cholesterol and a 10 mm Hg (6%) reduction in systolic blood pressure. CONCLUSIONS: In this prospective 5-week non-dairy vegetarian nutrition intervention with good adherence consistent with the 2019 ACC/AHA Guidelines in an at-risk AA population, markers of cardiovascular risk, cardiometabolism, and body weight were significantly reduced, including obesity, low-density lipoprotein cholesterol (LDLc) density, LP(a), inflammation, and ingestion of substrates mediating production of trimethylamine-N-oxide (TMAO). Albeit reduced, hs-CRP and suPAR, were not lowered consistently. This induced a significant decrease in the 10-year ASCVD risk in this AA cohort. If widely adopted, this could dramatically reduce and possibly eradicate, the racial disparity in ASCVD events and mortality, if 19% of the 21% increase is eliminated by this lifestyle change.

Associations between sinus tachycardia and adverse cardiovascular outcomes and mortality in cancer patients.

BACKGROUND: Sinus tachycardia in cancer reflects a significant multi-system organ stressor and disease, with sparse literature describing its clinical significance. We assessed cardiovascular (CV) and mortality prognostic implications of sinus tachycardia in cancer patients. METHODS: We conducted a case-control study of 622 cancer patients at a U.S. urban medical center from 2008 to 2016. Cases had ECG-confirmed sinus tachycardia [heart rate (HR) ≥100 bpm] in ≥3 different clinic visits within 1 year of cancer diagnosis excluding a history of pulmonary embolism, thyroid dysfunction, left ventricular ejection fraction <50%, atrial fibrillation/flutter, HR >180 bpm. Adverse CV outcomes (ACVO) were heart failure with preserved ejection fraction (HFpEF), HF with reduced EF (HFrEF), hospital admissions for HF exacerbation (AHFE), acute coronary syndrome (ACS). Regression analyses were conducted to examine the effect of sinus tachycardia on overall ACVO and survival. RESULTS: There were 51 cases, age and sex-matched with 571 controls (mean age 70±10, 60.5% women, 76.4% Caucasian). In multivariate analysis over a 10-year follow-up period, sinus tachycardia (HR ≥100 vs. <100 bpm) was an independent predictor of overall ACVO (OR 2.8, 95% CI: 1.4-5.5; P=0.006). There was increased incidence of HFrEF (OR 3.3, 95% CI: 1.6-6.5; P=0.004) and AHFE (OR 6.3, 95% CI: 1.6-28; P=0.023), but not HFpEF or ACS (P>0.05) compared with controls. Sinus tachycardia was a significant predictor of overall mortality after adjusting for significant covariates (HR 2.9, 95% CI 1.8-5; P<0.001). CONCLUSIONS: Independent of typical factors that affect cardiovascular disease, sinus tachycardia around the time of cancer treatment is associated with increased ACVO and mortality in cancer patients at 10 years of follow-up.

Prognostic significance of ischemic electrocardiographic changes with regadenoson stress myocardial perfusion imaging.

BACKGROUND: In patients undergoing regadenoson SPECT myocardial perfusion imaging (MPI), the prognostic value of ischemic ST-segment depression (ST↓) and the optimal ST↓ threshold have not been studied. METHODS: A retrospective cohort study of consecutive patients referred for regadenoson stress MPI was conducted. Patients with uninterpretable ECG were excluded. Two diagnostic thresholds of horizontal or downsloping ST↓ were studied, ≥ 0.5 mm and ≥ 1.0 mm. The primary endpoint was the composite major adverse cardiac events (MACE) of cardiac death, myocardial infarction, or coronary revascularization. RESULTS: Among 8615 subjects (mean age 62 ± 13 years; 55% women), 89 (1.0%) had ST↓ ≥ 1.0 mm and 133 (1.5%) had ST↓ ≥ 0.5 mm. Regadenoson-induced ST↓ was more common in women (P < .001). Mean follow-up was 2.5 ± 2.2 years. After multivariate adjustment, ST↓ ≥ 1.0 mm was associated with a non-significant increase in MACE risk (P = .069), irrespective to whether MPI was abnormal (P = .162) or normal (P = .214). Ischemic ST↓ ≥ 0.5 mm was independently associated with MACE in the entire cohort (HR 2.14; CI 1.38-3.32; P = .001), whether MPI is normal (HR 2.07; CI 1.07-4.04; P = .032) or abnormal (HR 2.24; CI 1.23-4.00; P = .007), after adjusting for clinical and imaging covariates. An ST↓ threshold of ≥ 0.5 mm provided greater incremental prognostic value beyond clinical and imaging parameters (Δχ2 = 12.78; P < .001) than ≥ 1.0 mm threshold (Δχ2 = 3.72; P = .093). CONCLUSION: Regadenoson-induced ischemic ST↓ is more common in women and it provides a modest independent prognostic value beyond MPI and clinical parameters. ST↓ ≥ 0.5 mm is a better threshold than ≥ 1.0 mm to define ECG evidence for regadenoson-induced myocardial ischemia.

The prognostic value of heart rate response during vasodilator stress myocardial perfusion imaging in patients with end-stage renal disease undergoing renal transplantation.

BACKGROUND: In asymptomatic end-stage renal disease (ESRD) patients undergoing vasodilator stress myocardial perfusion imaging (MPI) prior to renal transplantation (RT), the impact of pre-transplant heart rate response (HRR) to vasodilator stress on post-RT outcomes is unknown. METHODS: We analyzed a retrospective cohort of asymptomatic patients with ESRD who underwent a vasodilator stress SPECT-MPI and subsequently received RT. Blunted HRR was defined as HRR <28% for regadenoson stress and <20% for adenosine stress. The primary endpoint was major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. Clinical risk was assessed using the sum of risk factors set forth by the AHA/ACCF consensus statement on the assessment of RT candidates. RESULTS: Among 352 subjects, 140 had an abnormal pre-transplant HRR. During a mean follow-up of 3.2 ± 2.0 years, 85 (24%) MACEs were observed. Blunted HRR was associated with increased MACE risk (hazard ratio 1.72; 95% confidence interval 1.12-2.63, P = 0.013), and remained significant after adjustment for gender, sum of AHA/ACCF risk factors, summed stress score, baseline heart rate, and ß-blocker use. HRR was predictive of MACE in patients with normal MPI and irrespective of clinical risk. Blunted HRR was associated with a significant increase in post-operative (30-day) MACE risk (17.9% vs 8.5%; P = 0.009). CONCLUSION: In asymptomatic ESRD patients being evaluated for RT, a blunted pre-transplant HRR was predictive of post-RT MACE. HRR may be a valuable tool in the risk assessment of RT candidates.

Influence of breast reconstruction on technical aspects of echocardiographic image acquisition compared with physician-assessed image quality.

INTRODUCTION: Assessment of cardiac function after treatment for breast cancer relies on interval evaluation of ventricular function through echocardiography. Women who undergo mastectomy more frequently choose to undergo breast reconstruction with implant. This could impede assessment of cardiac function in those with left-sided implant. We aimed to examine whether left-sided breast reconstruction with tissue expanders (TE) affect echo image acquisition and quality, possibly affecting clinical decision-making. METHODS: A retrospective case-control study was conducted in 190 female breast cancer patients who had undergone breast reconstruction with TE at an urban academic center. Echocardiographic technical assessment and image quality were respectively classified as excellent/good or adequate/technically difficult by technicians; and excellent/good or adequate/poor by 2 board-certified cardiologist readers. Likelihood ratio was used to test multivariate associations between image quality and left-sided TE. RESULTS: We identified 32 women (81.3% white; mean age 48 years) with left-sided/bilateral TE, and 158 right-sided/no TE (76.6% white, mean age 57 years). In multivariable analyses, we found a statistically significant difference in technician-assessed difficulty in image acquisition between cases and controls (p = 0.01); but no differences in physician-assessed image quality between cases and controls (p = 0.09, Pearson's r = 0.467). CONCLUSIONS: Left-sided breast TE appears to affect the technical difficulty of echo image acquisition, but not physician-assessed echo image quality. This likely means that echo technicians absorb most of the impediments associated with imaging patients with breast TE such that the presence of TE has no bearing on downstream clinical decision-making associated with echo image quality.

The serum-based VeriStrat® test is associated with proinflammatory reactants and clinical outcome in non-small cell lung cancer patients.

BACKGROUND: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research. The aim of this study was to correlate VeriStrat status with other circulating biomarkers in advanced NSCLC patients - each with respect to clinical outcomes. METHODS: Serum samples were prospectively collected from 57 patients receiving salvage chemotherapy and 70 non-EGFR mutated patients receiving erlotinib. Patients were classified as either VeriStrat good or poor based on the VeriStrat test. Luminex immunoassays were used to measure circulating levels of 102 distinct biomarkers implicated in tumor aggressiveness and treatment resistance. A Cox PH model was used to evaluate associations between biomarker levels and clinical outcome, whereas the association of VeriStrat classifications with biomarker levels was assessed via the Mann-Whitney Rank Sum test. RESULTS: VeriStrat was prognostic for outcome within the erlotinib treated patients (HR = 0.29, p < 0.0001) and predictive of differential treatment benefit between erlotinib and chemotherapy ((interaction HR = 0.25; interaction p = 0.0035). A total of 27 biomarkers out of 102 unique analytes were found to be significantly associated with OS (Cox PH p ≤ 0.05), whereas 16 biomarkers were found to be associated with PFS. Thrombospondin-2, C-reactive protein, TNF-receptor I, and placental growth factor were the analytes most highly associated with OS, all with Cox PH p-values ≤0.0001. VeriStrat status was found to be significantly associated with 23 circulating biomarkers (Mann-Whitney Rank Sum p ≤ 0.05), 6 of which had p < 0.001, including C-reactive protein, IL-6, serum amyloid A, CYFRA 21.1, IGF-II, osteopontin, and ferritin. CONCLUSIONS: Strong associations were observed between survival and VeriStrat classifications as well as select circulating biomarkers associated with fibrosis, inflammation, and acute phase reactants as part of this study. The associations between these biomarkers and VeriStrat classification might have therapeutic implications for poor prognosis NSCLC patients, particularly with new immunotherapeutic treatment options.

Validation of a clinical pathway to assess asymptomatic renal transplant candidates using myocardial perfusion imaging.

BACKGROUND: An AHA/ACCF scientific statement proposed 8 risk factors to assess the need for noninvasive coronary artery disease (CAD) surveillance in asymptomatic patients undergoing evaluation for kidney transplantation. The clinical application of these risk factors and the role of noninvasive testing in this context have not been defined. METHODS AND RESULTS: We retrospectively followed a cohort of 581 consecutive kidney transplant recipients of whom 401 had pre-transplant radionuclide myocardial perfusion imaging (MPI) and 90 had pre-transplant coronary angiography. The sum of pre-transplant AHA/ACCF risk factors (age >60 years, hypertension, diabetes, cardiovascular disease, dyslipidemia, smoking, dialysis >1 year, left ventricular hypertrophy) was calculated. MPI scans were analyzed by a "blinded" reader. Patients were followed for a mean of 3.7 ± 2.3 years post-transplant for major adverse cardiac events (MACE), defined as cardiac death or non-fatal myocardial infarction. The sum of risk factors was associated with modest discriminatory capacity for obstructive angiographic CAD (area under the curve [AUC], 0.70; P = 0.004), 30-day post-operative MACE (AUC, 0.60; P = 0.036), and long-term MACE (AUC, 0.63; P < 0.001). A threshold of ≥3 risk factors was optimal for identifying patients at risk. MPI provided incremental predictive value for obstructive CAD (P = 0.02) and long-term MACE (P = 0.04) but not post-operative MACE (P = 0.56). MPI was best predictive of long-term MACE in intermediate risk (3-4 risk factors) patients. CONCLUSIONS: Asymptomatic kidney transplant candidates with ≥3 AHA/ACCF risk factors are at increased cardiac risk, and should be considered for noninvasive CAD surveillance. Intermediate risk patients (3-4 factors) benefit the most from pre-transplant MPI to define long-term MACE risk.

The significance of post-stress decrease in left ventricular ejection fraction in patients undergoing regadenoson stress gated SPECT myocardial perfusion imaging.

BACKGROUND: The significance of post-stress decrease in left ventricular ejection fraction (LVEF) with regadenoson stress gated SPECT (GSPECT) myocardial perfusion imaging (MPI) has not been studied. METHODS AND RESULTS: Consecutive patients who underwent rest/regadenoson stress GSPECT-MPI followed by coronary angiography within 6 months were analyzed. Change in LVEF by GSPECT-MPI was calculated as stress LVEF minus rest LVEF; a significant decrease was tested at 5% and 10% thresholds. In a diagnostic cohort of 793 subjects, LVEF change was not predictive of severe/extensive coronary artery disease (area under the curve, 0.50; 95% confidence interval, 0.44-0.57; P = 0.946). There was no significant difference in the rates of severe/extensive coronary artery disease in patients with or without a decrease in LVEF, irrespective of MPI findings. In an outcome cohort of the 929 subjects followed for 30 ± 16 months, post-regadenoson stress decrease in LVEF was not associated with increased risk of the composite endpoint of cardiac death or myocardial infarction or in the risk of coronary revascularization. CONCLUSIONS: In patients selected to undergo coronary angiography following regadenoson stress GSPECT-MPI, a decrease in LVEF after regadenoson stress is not predictive of severe/extensive CAD or adverse clinical outcomes, irrespective of MPI findings.

Impact of cachexia on outcomes in aggressive lymphomas.

Cancer cachexia is defined as a state of involuntary weight loss, attributed to altered body composition with muscle mass loss and/or loss of adiposity. Identifying the association between cancer cachexia and outcomes may pave the way for novel agents that target the cancer cachexia process. Clinical parameters for measurement of cancer cachexia are needed. We conducted a single-institution retrospective analysis that included 86 NHL patients with the aim of identifying an association between cancer cachexia and outcomes in aggressive lymphomas using the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87-93, 15). Impact of cachexia factors on progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test and Cox proportional hazards regression. Patients were dichotomized around the median CXI into "non-cachectic" (CXI ≥49.8, n = 41) and "cachectic" (CXI <49.8, n = 40) groups. Cachectic patients had significantly worse PFS (HR 2.18, p = 0.044) and OS (HR = 4.05, p = 0.004) than non-cachectic patients. Cachexia as defined by the CXI is prognostic in aggressive lymphomas and implies that novel therapeutic strategies directed at reversing cachexia may improve survival in this population.

Transposition of Great Arteries with Complex Coronary Artery Variants: Time-Related Events Following Arterial Switch Operation.

Coronary artery anatomy represents a challenging and, often, determining predictor of outcome in an arterial switch operation (ASO). Impact of specific coronary artery variants, such as single, intramural and inverted, on time-related events following ASO, is, yet, to be determined. We sought to compare early and late outcomes within the group of nonstandard coronary artery variants. Patients who underwent ASO from January 1995 to October 2010 were reviewed. Patients with coronary artery variants other than L1Cx1R2 ("standard" by Leiden classification) were included. Patients with single, intramural and inverted coronary artery variants incorporated in group A. All other nonstandard coronary variants incorporated in group B. Demographics, perioperative variables, early and late outcomes were assessed. Of the 123 ASO, 24 patients (19.5%) with nonstandard coronary variant were studied. Thirteen were in group A and 11 in group B. There were two early deaths (1 in group A and 1 in group B) (p > 0.05). There is one death early after hospital discharge (group A). Mean follow-up was 59.4 ± 55.1 months. There was no structural coronary artery failure after hospital discharge following ASO. Freedom from any reintervention at 8 years was (78.3 ± 9.6%) (p 0.55) with no late neo-aortic or mitral valve intervention. ASO with single, intramural or inverted coronary artery course carries no added longitudinal risk for structural or flow impairment within the group of nonstandard coronary artery variants. There is an early hazard period with no late survival attrition. Aortic arch repair as part of staged strategy prior to ASO might influence early and late outcome.

Usefulness of Mean Platelet Volume to Predict Significant Coronary Artery Disease in Patients With Non-ST-Elevation Acute Coronary Syndromes.

Acute coronary syndrome (ACS) is characterized by unstable plaque with thrombotic process involving central role of platelets. The diagnosis and prediction of significant coronary artery disease (CAD) in non-ST-elevation ACS (NSTE-ACS) can be challenging. The central role of platelets in acute atherothrombosis in NSTE-ACS spurred appreciable interest in the diagnostic and predictive role of platelet activity. Mean platelet volume (MPV) is one of the most promising laboratory markers in patients with CAD. This retrospective study was designed to investigate the diagnostic and predictive value of high MPV levels in patients with NSTE-ACS with significant CAD. A total of 213 patients (men 53%, mean age 61 ± 12.3 years) with NSTE-ACS were enrolled from 2011 to 2016 from 2 teaching hospitals. Patients' demographic, laboratory, and angiographic data were collected. Significant CAD was defined as ≥70% stenosis in at least 1 major coronary artery. Patients with high MPV (MPV ≥9 fl) had more significant CAD (55% vs 35%, p = 0.005), lower platelet count (204 ± 59 × 1,000/µl vs 246 ± 56 × 1,000/µl, p = 0.001), and higher HbA1c (6.9 vs 6.4, p = 0.02). Patients with significant CAD had higher MPV level (9.2 ± 1.07 vs 8.6 ± 1.03 fl, p = 0.001), higher MPV/platelet ratio (0.46 vs 0.40, p = 0.01), older age (64.5 ± 11 vs 59.2 ± 12 years, p = 0.02), and lower high-density lipoprotein level (42 ± 12 vs 47 ± 16, p = 0.01). Multivariate analysis showed that increased age, high MPV, high troponin, and low high-density lipoprotein levels were associated with significant CAD. Patients with high MPV along with high troponin level demonstrated a 4.8-fold increased risk for significant CAD compared to those with normal MPV and high troponin (odds ratio 4.8, 95% confidence interval 1.31 to 17.6, p = 0.001). In conclusion, considering high MPV in the context of elevated troponin level increases the predictive value of screening for significant CAD, and this result may help determine who is most likely to benefit from cardiac catheterization.

Impact of integrating heart rate response with perfusion imaging on the prognostic value of regadenoson SPECT myocardial perfusion imaging in patients with end-stage renal disease.

BACKGROUND: We investigated whether integrating heart rate response (HRR) to regadenoson with myocardial perfusion imaging (MPI) analysis can enhance risk prediction in end-stage renal disease (ESRD) patients. METHODS AND RESULTS: We prospectively followed 303 ESRD patients after regadenoson stress MPI for a mean of 35 months. Normal HRR to regadenoson was defined as ≥28% increase from baseline. Normal MPI was defined as a summed stress score ≤3 and left ventricular ejection fraction ≥50%. The study cohort was divided in four groups based on various combinations of normal/abnormal HRR and MPI. There was a step-wise increase in the risk of primary endpoint of all-cause death and the composite secondary endpoint of cardiac death or myocardial infarction; patients with Normal MPI/Normal HRR had the lowest event rates and those with Abnormal MPI/Abnormal HRR had the highest, whereas subjects with Abnormal MPI/Normal HRR and Normal MPI/Abnormal HRR had intermediate event rates. This pattern was maintained after adjusting for important clinical covariates. CONCLUSION: In ESRD patients, integrating HRR to vasodilator stress with MPI interpretation improves risk stratification. Normal HRR/Normal MPI identify truly low-risk group, whereas abnormal MPI or abnormal HRR portrays elevated risk.

Impact of a regimented aminophylline administration protocol on the burden of regadenoson-induced ischemia detected by SPECT myocardial perfusion imaging.

BACKGROUND: In patients undergoing regadenoson SPECT myocardial perfusion imaging (MPI), it is unknown how soon and at which dose intravenous aminophylline can be administered to reverse regadenoson-related adverse effects without blunting stress-induced myocardial ischemia. METHODS AND RESULTS: We analyzed the pooled database of the ASSUAGE and ASSUAGE-CKD trials (n = 548). These were double-blinded, placebo-controlled, randomized clinical trials in which 75 mg of aminophylline or placebo was administered intravenously 90 seconds following 99mTc-tetrofosmin injection. There were no statistically significant differences in summed difference score (SDS) burden (P = .87) and in the rates of myocardial ischemia (SDS ≥ 2) (P = .93) between the aminophylline (n = 274) and placebo (n = 274) groups. There was no interaction between aminophylline use and SDS as a determinant of the composite endpoint of cardiac death or MI (P = .32) or the composite endpoint of cardiac death, MI, or coronary revascularization (P = .92). CONCLUSION: In patients undergoing regadenoson-stress SPECT-MPI, the intravenous administration of 75 mg of aminophylline as early as 90 seconds after radioisotope injection does not seem to attenuate the burden of myocardial ischemia.

The prognostic value of regadenoson SPECT myocardial perfusion imaging in patients with end-stage renal disease.

BACKGROUND: The prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) has not been specifically studied in patients with end-stage renal disease (ESRD). METHODS AND RESULTS: We prospectively followed ESRD patients enrolled in the ASSUAGE and ASSUAGE-CKD trials in which they received regadenoson-stress 99mTc-tetrofosmin SPECT-MPI. Images were semiquantitatively analyzed by an investigator blinded to clinical and outcome data. Patients were followed for cardiac death, myocardial infarction (MI), and coronary revascularization (CR). Revascularizations occurring >90 days post-MPI were considered "late" events. Survival analysis was performed using Cox regression models, adjusting for age, gender, diabetes, dyslipidemia, smoking, and known coronary artery disease. We analyzed 303 patients (mean age 54 years; 64% men), who were followed for 35 ± 10 months. Adjusting for clinical covariates, abnormal regadenoson-stress MPI (SSS ≥ 4) was associated with increased risk of the composite of cardiac death or MI (23.9% vs 14.4%; HR 1.88; CI 1.04-3.41; P = .037) and the composite of cardiac death, MI, or late CR (27.3% vs 16.7%; HR 1.80; CI 1.03-3.14; P = .039). Adjusting for clinical covariates, regadenoson-induced myocardial ischemia (SDS ≥ 2) was associated with increased rate of the composite endpoint of cardiac death, MI, or CR (33.3% vs 16.9%; HR 1.97; CI 1.19-3.27; P = .008). CONCLUSION: Regadenoson-stress SPECT-MPI provides a significant prognostic value in patients with ESRD. ESRD patients with normal SPECT-MPI have relatively high adverse event rates.

The Use of Speckle Tracking Echocardiography for Early Detection of Myocardial Dysfunction in Patients with Duchenne Muscular Dystrophy.

Cardiac complications are the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Two-dimensional echocardiography is the current standard for monitoring of LV systolic function in these patients, but it might not detect early systolic dysfunction. The current study examined the use of speckle tracking echocardiography (STE) to detect early signs of cardiac dysfunction in DMD patients. A retrospective review of charts and offline strain analysis of transthoracic echocardiographic studies of DMD patients at our institution from April 2014 to January 2015 were performed and compared to age-matched healthy male subjects. Nineteen DMD patients (age range 12.6 ± 3.1 years) with normal ejection fraction and shortening fraction were compared with sixteen controls. The global circumferential strain was lower in DMD patients compared with controls (-14.7 ± 4.7 vs. -23.1 ± 2.9 %, respectively, p value: 0.001). Circumferential strain measured at basal, mid-ventricular and apical parasternal short-axis views was lower in DMD patients compared with controls. Segmental circumferential strain was lower in DMD patients in most segments compared with controls. The global longitudinal strain was lower in DMD patients compared with controls (-13.6 ± 5 vs. -18.8 ± 3 %, respectively, p value: 0.001). Segmental longitudinal strain measured in various segments was lower in DMD patients compared with controls. DMD patients can have occult cardiovascular dysfunction as shown by reduction in circumferential and longitudinal strain measurements with STE despite normal standard echocardiographic parameters. The clinical significance of early detection of cardiac dysfunction in these patients warrants further studies.

Prognostic value of heart rate response during regadenoson stress myocardial perfusion imaging in patients with end stage renal disease.

BACKGROUND: Blunted heart rate response (HRR) to vasodilator stress agents is associated with worse outcomes. There are limited data assessing the effect of impaired HRR to regadenoson among patients with end-stage renal disease (ESRD) undergoing stress myocardial perfusion imaging (MPI). METHODS: We prospectively followed patients with ESRD enrolled in the ASSUAGE and ASSUAGE-CKD trials. HRR was defined as 100*(peak stress heart rate-resting heart rate)/resting heart rate. Study cohort was dichotomized to blunted and normal HRR groups according to an established median HRR value <28% or ≥28%, which were propensity-score matched based on 22 clinical and imaging covariates. The Primary endpoint was all-cause death. The secondary cardiac-specific endpoints included: (1) the composite endpoint of cardiac death or myocardial infarction; (2) the composite endpoint of cardiac death, myocardial infarction, or late (>90 days) coronary revascularization. RESULTS: There were 303 patients followed for 35 ± 10 months. In the entire cohort, there was a stepwise increase in the rates of death and all secondary endpoints with worsening HRR (P values ≤.001). Blunted HRR (<28%) was associated with increased risk of death (unadjusted hazard ratio 4.10 [1.98-8.46], P < .001) and all secondary endpoints (P ≤ .001). After multivariate adjustment, HRR remained an independent predictor of mortality and secondary endpoints whether used as continuous or dichotomous variable, and added incremental prognostic value for all-cause death (P = .046). Blunted HRR was associated with increased event rate among patients with normal myocardial perfusion (P = .001) and abnormal perfusion (P = .053). In the propensity-matched cohort of 132 patients (66 in each group), blunted HRR was associated with significant increase in all-cause death (21% vs. 5%, HR 5.09 [1.46-17.7], P=.011), and similarly for the secondary endpoints. CONCLUSION: Blunted HRR (<28%) to regadenoson is a strong and independent predictor of death and cardiovascular events in patients with ESRD and adds incremental prognostic value.

Diagnostic and prognostic significance of ischemic electrocardiographic changes with regadenoson-stress myocardial perfusion imaging.

BACKGROUND: The diagnostic and prognostic value of regadenoson-induced ST-segment depression (ST↓) is not defined. Due to the low incidence of ST↓ ≥1.0 mm with vasodilator stress, a lower threshold to define ischemic ECG response may provide improved clinical utility. METHODS: We conducted a retrospective cohort study of patients who underwent regadenoson-stress SPECT myocardial perfusion imaging (MPI) followed by coronary angiography within 6 months. Ischemic ST↓ was defined as ≥0.5 mm. The prevalence of angiographically severe coronary artery disease (CAD) and the rates of major adverse cardiac events (MACE) including cardiac death, myocardial infarction, and coronary revascularization were determined. RESULTS: In a diagnostic cohort of 629 subjects, 117 (18.6%) had ST↓ ≥0.5 mm. Severe CAD was more prevalent in the ST↓ ≥0.5 vs ST <0.5 group (13.7% vs 5.3%, P = .001). Among patients with normal MPI (n = 229), the prevalence of severe CAD was higher in the ST↓ ≥0.5 group (8.2% vs 2.2%, P = .04). Adjusting for clinical and imaging covariates, ST↓ ≥0.5 mm was independently predictive of severe CAD [odds ratio = 3.37, 95% confidence interval (CI) = 1.67-6.83, P = .001], and provided incremental diagnostic value (Chi square increment = 10.3, P = .001). In an outcome cohort of 748 subjects, after adjusting for clinical and imaging covariates, ST↓ ≥0.5 mm was associated with increased MACE rate in the entire cohort [hazard ratio = 1.41, CI 1.01-1.96, P = .04] and in the subgroup of patients with normal MPI [hazard ratio = 2.2, CI 1.11-4.39, P = .02], and provided incremental prognostic value (Chi square increment = 3.9, P = .049). A diagnostic ST↓ threshold of 0.5 mm provided greater discriminatory capacity than a 1.0 mm cutoff (P = .03). CONCLUSIONS: Among patients selected to undergo coronary angiography, regadenoson-induced ST↓ ≥0.5 mm was associated with higher rates of severe CAD and MACE, irrespective of MPI finding.