Ronald Mastouri

Current noninvasive imaging techniques for detection of coronary artery disease

The development and widespread use of noninvasive imaging techniques have contributed to the improvement in evaluation of patients with known or suspected coronary artery disease. Stress echocardiography and single-photon computed tomography are well-established noninvasive techniques with a proven track record for the diagnosis of coronary atherosclerosis. These modalities are generally widely available and provide a relatively high sensitivity and specificity along with an incremental value over clinical risk factors for detection of coronary artery disease. PET has a high diagnostic performance but continues to have limited clinical use because of the high expense of the dedicated equipment and difficulties in obtaining adequate radionuclides. Cardiac MRI and multislice computed tomography constitute the most recent addition to the cardiac imaging armamentarium. Cardiac MRI offers a comprehensive cardiac evaluation, which includes wall-motion analysis, myocardial tissue morphology, rest and stress first-pass myocardial perfusion, as well as ventricular systolic function. Cardiac computed tomography allows coronary calcium scanning along with noninvasive anatomic assessment of the coronary tree. It can be combined with functional imaging to provide a complete evaluation of the presence and physiological significance of the atherosclerotic coronary disease. No single imaging modality has been proven to be superior overall. Available tests all have advantages and drawbacks, and none can be considered suitable for all patients. The choice of the imaging method should be tailored to each person based on the clinical judgment of the a priori risk of cardiac event, clinical history and local expertise.

Prediction of Ischemic Events by Anatomic M-mode Strain Rate Stress Echocardiography

OBJECTIVE We assessed the prognostic value of anatomic M-mode strain rate stress echocardiography (SRSE) in patients with known or suspected coronary artery disease. Previous studies showing that M-mode SRSE may be an accurate method for detection of coronary artery disease suggest that this technique may be useful for risk stratification. METHODS M-mode SRSE, using a color-coded display of strain rate (SR), was performed in 358 patients (48, dobutamine; 68, bicycle; 242, treadmill). SR was graded by visual assessment of the color-coded display in 12 apical segments. Abnormal rest SR was defined as SR more positive than -1/s (green-yellow). Ischemia was defined by the development of post-systolic shortening or lack of improvement of SR to more negative than -2/s (brown hue) with stress. Patients were followed for cardiac events. RESULTS Twelve patients with early intervention for an abnormal two-dimensional stress echocardiogram or stress electrocardiogram were excluded. Follow-up (mean 10.7 months) was completed in 98% (338/346) of the remaining patients. Events occurred in 1.7% (4/230) of patients with normal SRSE compared with 10% (11/108) with abnormal SRSE (P = .002). The annualized hard event (infarction, death) rate in those with normal SRSE was 0.5% versus 7.2% in those with abnormal SRSE (P = .001). Smoking (P = .048, relative risk 2.91), nitrate use (P = .001, relative risk 7.81), and the severity of the abnormality on SRSE (P = .009, relative risk 1.75) independently predicted events. Wall motion assessment was not predictive. Patients with normal SRSE had better event-free survival compared with those with abnormal SRSE (P < .001). CONCLUSION SRSE is an independent predictor of outcome. A normal SRSE predicts a low risk of infarction or death in short-term follow-up.

Noninvasive imaging techniques of constrictive pericarditis

Constrictive pericarditis (CP) is the result of scarring and loss of elasticity of the pericardial sac, resulting in external impedance of cardiac filling. It can occur after virtually any pericardial disease process. Patients typically present with signs and symptoms of right heart failure and/or low cardiac output. An important pathophysiological hallmark of CP is exaggerated ventricular interdependence and impaired diastolic filling. Echocardiography is the initial imaging modality for diagnosis of CP. Unfortunately, no echocardiographic sign or combination of signs is pathognomonic for CP. CT scan and cardiac MRI are other imaging techniques that can provide incremental diagnostic information. CT scan can easily detect pericardial thickening and calcification, while cardiac MRI provides a comprehensive evaluation of the pericardium, myocardium and cardiac physiology. Occasionally, a multimodality approach needs to be considered for the conclusive diagnosis of CP.

Genome-wide association study for anthracycline-induced congestive heart failure

Purpose: Anthracycline-induced congestive heart failure (CHF) is a rare but serious toxicity associated with this commonly employed anticancer therapy. The ability to predict which patients might be at increased risk prior to exposure would be valuable to optimally counsel risk-to-benefit ratio for each patient. Herein, we present a genome-wide approach for biomarker discovery with two validation cohorts to predict CHF from adult patients planning to receive anthracycline. Experimental Design: We performed a genome-wide association study in 3,431 patients from the randomized phase III adjuvant breast cancer trial E5103 to identify single nucleotide polymorphism (SNP) genotypes associated with an increased risk of anthracycline-induced CHF. We further attempted candidate validation in two independent phase III adjuvant trials, E1199 and BEATRICE. Results: When evaluating for cardiologist-adjudicated CHF, 11 SNPs had a P value <10−5, of which nine independent chromosomal regions were associated with increased risk. Validation of the top two SNPs in E1199 revealed one SNP rs28714259 that demonstrated a borderline increased CHF risk (P = 0.04, OR = 1.9). rs28714259 was subsequently tested in BEATRICE and was significantly associated with a decreased left ventricular ejection fraction (P = 0.018, OR = 4.2). Conclusions: rs28714259 represents a validated SNP that is associated with anthracycline-induced CHF in three independent, phase III adjuvant breast cancer clinical trials. Clin Cancer Res; 23(1); 43–51. ©2016 AACR.

Frequency, Time Course, and Possible Causes of Right Ventricular Systolic Dysfunction after Cardiac Transplantation: A Single Center Experience

Background: The frequency and causes of right ventricular (RV) systolic dysfunction early after cardiac transplantation are not well defined. Methods: We investigated the prevalence and causes of RV dysfunction in 27 heart transplant recipients, as measured by lateral tricuspid annular plane excursion (TAPSE) and fractional area change (FAC) at a mean of 15 ± 11 days after transplant. Tissue Doppler imaging was used to assess systolic time velocity integral (TVI) of the RV basal free wall. A subset of 22 patients had follow‐up TAPSE measurement at 406 ± 121 days. Results: RV systolic dysfunction, defined as TAPSE > 2 standard deviation (SD) below values in a control group, was present in 100% (27/27) of patients (P < 0.05). FAC was also significantly lower in patients compared with controls (P < 0.0001). TVI confirmed the presence of RV dysfunction in all 16 patients with both TAPSE and TVI (P < 0.05). Ischemic time (P = 0.017) and posttransplant tricuspid regurgitation (P = 0.024) were independent predictors of early RV dysfunction (r = 0.753). On follow‐up, RV function improved in 15 of 22 patients but all patients remained with TAPSE > 2 SD below controls. Conclusion: This study showed that 100% of patients had reduced RV function early after transplant. Two thirds of patients had partial recovery of RV function during the first year. In all patients, however, RV function remained significantly lower than in controls.

Effect of Body Mass Index on Left Ventricular Mass in Career Male Firefighters

Left ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD) events; increased LV mass is common among US firefighters and plays a major role in firefighter sudden cardiac death. We aim to identify significant predictors of LV mass among firefighters. Cross-sectional study of 400 career male firefighters selected by an enriched randomization strategy. Weighted analyses were performed based on the total number of risk factors per subject with inverse probability weighting. LV mass was assessed by echocardiography (ECHO) and cardiac magnetic resonance, and normalized (indexed) for height. CVD risk parameters included vital signs at rest, body mass index (BMI)–defined obesity, obstructive sleep apnea risk, low cardiorespiratory fitness, and physical activity. Linear regression models were performed. In multivariate analyses, BMI was the only consistent significant independent predictor of LV mass indexes (all, p <0.001). A 1-unit decrease in BMI was associated with 1-unit (g/m1.7) reduction of LV mass/height1.7 after adjustment for age, obstructive sleep apnea risk, and cardiorespiratory fitness. In conclusion, after height-indexing ECHO-measured and cardiac magnetic resonance–measured LV mass, BMI was found to be a major driver of LV mass among firefighters. Our findings taken together with previous research suggest that reducing obesity will improve CVD risk profiles and decrease on-duty CVD and sudden cardiac death events in the fire service. Our results may also support targeted noninvasive screening for LV hypertrophy with ECHO among obese firefighters.

Derivation of a Screening Tool to Identify Patients with Right Ventricular Dysfunction or Tricuspid Regurgitation after Negative Computerized Tomographic Pulmonary Angiography of the Chest

Many dyspneic patients who undergo computerized tomographic pulmonary angiography (CTPA) for presumed acute pulmonary embolism (PE) have no identified cause for their dyspnea yet have persistent symptoms, leading to more CTPA scanning. Right ventricular (RV) dysfunction or overload can signal treatable causes of dyspnea. We report the rate of isolated RV dysfunction or overload after negative CTPA and derive a clinical decision rule (CDR). We performed secondary analysis of a multicenter study of diagnostic accuracy for PE. Inclusion required persistent dyspnea and no PE. Echocardiography was ordered at clinician discretion. A characterization of isolated RV dysfunction or overload required normal left ventricular function and RV hypokinesis, or estimated RV systolic pressure of at least 40 mmHg. The CDR was derived from bivariate analysis of 97 candidate variables, followed by multivariate logistic regression. Of 647 patients, 431 had no PE and persistent dyspnea, and 184 (43%) of these 431 had echocardiography ordered. Of these, 64 patients (35% [95% confidence interval (CI): 28%–42%]) had isolated RV dysfunction or overload, and these patients were significantly more likely to have a repeat CTPA within 90 days (P = .02, χ 2 test). From univariate analysis, 4 variables predicted isolated RV dysfunction: complete right bundle branch block, normal CTPA scan, active malignancy, and CTPA with infiltrate, the last negatively. Logistic regression found only normal CTPA scanning significant. The final rule (persistent dyspnea + normal CTPA scan) had a positive predictive value of 53% (95% CI: 37%–69%). We conclude that a simple CDR consisting of persistent dyspnea plus a normal CTPA scan predicts a high probability of isolated RV dysfunction or overload on echocardiography.

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath

BACKGROUND Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes.

Caffeine Consumption and Heart Rate and Blood Pressure Response to Regadenoson

Background Current guidelines recommend that caffeinated products should be avoided for at least 12 hours prior to regadenoson administration. We intended to examine the effect of caffeine consumption and of timing of last dose on hemodynamic effects after regadenoson administration for cardiac stress testing. Methods 332 subjects undergoing regadenoson stress testing were enrolled. Baseline characteristics, habits of coffee/caffeine exposure, baseline vital signs and change in heart rate, blood pressure, percent of maximal predicted heart rate, and percent change in heart rate were prospectively collected. Results Non-coffee drinkers (group 1) (73 subjects) and subjects who last drank coffee >24 hours (group 3) (139 subjects) prior to regadenoson did not demonstrate any difference in systolic blood pressure, heart rate change, maximal predicted heart rate and percent change in heart rate. Systolic blood pressure change (15.2±17.1 vs. 7.2±10.2 mmHg, p = 0.001), heart rate change (32.2±14 vs. 27.3±9.6 bpm, p = 0.038) and maximal predicted heart rate (65.5±15.6 vs. 60.7±8.6%, p = 0.038) were significantly higher in non-coffee drinkers (group 1) compared to those who drank coffee 12–24 hours prior (group 2) (108 subjects). Subjects who drank coffee >24 hours prior (group 3) exhibited higher systolic blood pressure change (13±15.8 vs. 7±10.2, p = 0.007), and heart rate change (32.1±15.3 vs. 27.3±9.6, p = 0.017) as compared to those who drank coffee 12–24 hours prior to testing (group 2). Conclusions Caffeine exposure 12–24 hours prior to regadenoson administration attenuates the vasoactive effects of regadenoson, as evidenced by a blunted rise in heart rate and systolic blood pressure. These results suggest that caffeine exposure within 24 hours may reduce the effects of regadenoson administered for vasodilatory cardiac stress testing.

PROGNOSTIC VALUE OF STRAIN ECHOCARDIOGRAPHY IN PATIENTS UNDERGOING CHEMOTHERAPY

Cardiotoxicity is a known complication of chemotherapy. Left ventricular ejection (EF) fraction has been historically used to monitor cardiac function but fails to detect early signs of cardiotoxicity. Early data suggest that reduction in longitudinal strain may be a more sensitive marker of