The utility of dobutamine stress echocardiography for the diagnosis of coronary artery disease in the HIV population.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has increased human immunodeficiency virus (HIV) patient longevity by 10-15 years. This increased longevity has habituated new cardiovascular complications, in particular, accelerated coronary artery disease (CAD). Although dobutamine stress echocardiography (DSE) is a highly sensitive and specific test for the noninvasive detection of underlying CAD in the general population, its utility in the HIV population remains unknown. OBJECTIVE: The objective of the current study was to assess the validity of DSE for the noninvasive detection of underlying symptomatic CAD in the HIV population using cardiac catheterization as the gold standard. METHODS AND RESULTS: A total of 40 HIV positive patients (mean 49 ± 8 years; 31 males) between 2006 and 2009 inclusively underwent routine DSE and coronary angiography. A positive stress echo with new wall motion abnormalities was detected in 9 (23%) individuals. Coronary angiography, following DSE, detected obstructive CAD in 12 (30%) individuals. For the diagnosis of obstructive CAD, DSE has a sensitivity of 67%, specificity of 97%, positive predictive value (PPV) of 89%, and negative predictive value (NPV) of 87%. CONCLUSION: In this select HIV population, DSE was highly specific for the noninvasive detection of obstructive CAD.

Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study.

Background The incidence and management of trastuzumab-mediated cardiotoxicity outside of clinical trials has not been well described. Objective and methods The aim of the study was to retrospectively evaluate the incidence of cardiac dysfunction, characterize its natural history, and identify the degree of reversibility using cardiac MRI, in a population of HER-2 positive breast cancer patients receiving trastuzumab in the adjuvant setting. Results Out of 152 patients (mean age 52 +/- 10 years), 36 (24%) developed trastuzumab mediated cardiomyopathy, the majority asymptomatic. Factors that predicted the development of trastuzumab mediated cardiac dysfunction were a pre-existing history of hypertension, smoking history, and a family history of coronary artery disease. Within 3 months of treatment with trastuzumab, there was a difference in LVEF between the normal cohort and those patients who developed LV systolic dysfunction (61 +/- 5% vs. 51 +/- 8%, P < 0.01). During the 6-month-followup, 34/36 patients demonstrated subepicardial linear delayed enhancement of the lateral wall of the left ventricle on cardiac MRI, suggesting trastuzumab induced myocarditis. Conclusion Approximately 1 in 4 women may develop LV systolic dysfunction after treatment with adjuvant trastuzumab, necessitating careful patient selection and close serial monitoring using noninvasive cardiac imaging.

Is the presence of mitral annular calcification associated with poor left atrial function?

INTRODUCTION: Mitral annular calcification (MAC) is characterized by calcium and lipid deposition in the annular fibrosa of the mitral valve. MAC is associated with cardiovascular events but little is known of its association with left atrial (LA) function. METHODS: We prospectively obtained 12-lead electrocardiograms (ECGs) and transthoracic echocardiograms (TTE) on patients scheduled for nonemergent echocardiographic assessment at a tertiary care hospital. MAC was graded as 0 = none, 1 = mild, 2 = moderate, 3 = severe. LA linear and volume measurements (stroke volume, LA passive emptying fraction, LA active emptying fraction and LA kinetic energy) were done specifically in addition to commonly measured TTE parameters. RESULTS: From the 124 considered for the study, 72 patients remained (aged 68+/-18 years; 44% male) after excluding those with poor ECG tracings and/or poor TTE images. Eighteen patients had MAC; mild MAC = 14, moderate MAC = 3, severe MAC = 1. When patients with MAC were compared to those without MAC, no significant difference was noted, except for LA linear dimension index (2.1+/-0.4 vs. 1.9+/-0.3 cm/m(2); P = 0.03). For those with mild and moderate MAC, a trend was noted toward lower LA function with increasing MAC severity. In addition, significant differences were noted between those with and without interatrial conduction delay, where those with such delay had significantly impaired LA stroke volume (9.8+/-3 vs. 19.93+/-4 ml; P < 0.0001), LA active emptying fraction (18.83+/-8 vs. 65.71+/-9%; P < 0.0001) and LA total/reservoir fraction (39.54+/-6 vs. 75.1+/-6%; P < 0.0001). CONCLUSIONS: MAC is associated with increase in LA linear dimension on TTE and may be equally represented with lower overall LA function. Further study in a much larger cohort is warranted to delineate these and other potential associations of MAC.

Stress echocardiography: abnormal tissue Doppler imaging in the absence of cardiac allograft vasculopathy in heart transplant recipients.

BACKGROUND: The most significant predictor of long-term survival in heart transplant patients is the development of accelerated cardiac allograft vasculopathy (CAV). Several studies have demonstrated the usefulness of dobutamine stress echocardiography (DSE) for screening CAV, by detecting regional wall motion abnormalities. Tissue Doppler imaging (TDI)-derived indices during DSE allow for the early detection of ischemic heart disease (IHD), prior to a reduction in regional or global systolic function. These indices include a reduction in annular systolic velocity (S'), a decrease in early diastolic annular velocity (E'), and prolongation of time to E'. In cardiac transplant patients, the application of these TDI abnormalities during DSE remains unknown. OBJECTIVE: The objective of this study was to evaluate the pattern of (TDI-derived indices of systolic and diastolic function during DSE in cardiac transplant patients without evidence of CAV. METHODS: A retrospective evaluation of 30 patients (mean age 54 +/- 11 years) who had both DSE and coronary angiography was performed. The control group consisted of 15 patients referred to rule out coronary artery disease while the study group consisted of 15 cardiac transplant patients referred for routine annual follow-up. During each stage of DSE, tissue Doppler measurements of systolic (S'), early (E'), and late (A') diastolic velocities of the lateral annulus were taken. RESULTS: All 30 patients had normal DSE based on systolic regional function and normal coronary angiograms with no stenosis >50%. There was no difference in hemodynamic parameters during the DSE at baseline and with stress. Despite normal coronaries, cardiac transplant patients demonstrated lower S', E', and A' velocities at peak stress compared to the control patients. CONCLUSION: Dobutamine-induced augmentation of TDI velocities of the lateral annulus, normally observed in the absence of ischemia in nontransplanted adults, is reduced in cardiac transplant recipients.

Differences in treadmill exercise tolerance parameters between patients with partial and advanced interatrial depolarization abnormality.

Advanced interatrial block (aIAB) is considerably much less common than partial interatrial block (pIAB), occuring in <2% of the elderly hospitalized population. Less is, therefore, known of the true clinical burden of aIAB, particularly in relation to graded exercise. Therefore, 12 patients with aIAB and 30 patients with pIAB who performed a baseline exercise tolerance test and had a repeat test performed > or = 2 years later were included in the study. Exercise tolerance, echocardiographic findings, and major adverse cardiovascular events were compared. Left atrial size progressed at a significantly faster rate in those with aIAB. In addition, Duke Prognostic Treadmill scores were significantly lower on follow-up in those patients with aIAB. Overall, patients with aIAB had significantly greater left atrial size (48.3 +/- 9 vs 42.8 +/- 4 mm, p < 0.01) and significantly lower Duke Prognostic Treadmill scores than those with pIAB (-0.2 +/- 5 vs 4.1 +/- 4, p < 0.05). There were, however, no significant differences in the occurence of major adverse cardiovascular events. In conclusion, left atrial size progressed at a significantly faster rate but Duke Prognostic Treadmill scores were significantly lower in those with aIAB compared with patients with pIAB after > or = 2 years of follow-up. Further study is required to determine whether patients with aIAB require follow-up echocardiography and/or exercise tolerance tests for optimal risk stratification.

Clinical utility of tissue Doppler imaging in patients with acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Echocardiography is widely used in the management of patients with cardiogenic shock (CS). Left ventricular ejection fraction (EF) has been shown to be an independent predictor of survival in CS. Tissue Doppler Imaging (TDI) is a sensitive echocardiographic technique that allows for the early quantitative assessment of regional left ventricular dysfunction. TDI derived indices, including systolic velocity (S'), early (E') and late (A') diastolic velocities of the lateral mitral annulus, are reduced in heart failure patients (EF < 30%) and portend a poor prognosis. In CS patients, the application of TDI prior to revascularization remains unknown. OBJECTIVE: To characterize TDI derived indices in CS patients as compared to patients with chronic CHF. METHODS: Between 2006 and 2007, 100 patients were retrospectively evaluated who underwent echocardiography for assessment of LV systolic function. This population included: Group I) 50 patients (30 males, 57 +/- 13 years) with chronic CHF as controls; and Group II) 50 patients (29 males, 58 +/- 10 years) with CS. Spectral Doppler indices including peak early (E) and late (A) transmitral velocities, E/A ratio, and E-wave deceleration time were determined. Tissue Doppler indices including S', E' and A' velocities of the lateral annulus were measured. RESULTS: Of the entire cohort, the mean LVEF was 25 +/- 5%. Cardiogenic shock patients demonstrated significantly lower lateral S', E' and a higher E/E' ratio (p < 0.01), as compared to CHF patients. The in-hospital mortality in the CHF cohort was 5% as compared to the CS group with an in hospital mortality of 40%. In the subset of CS patients (n = 30) who survived, the mean S' at presentation was higher as compared to those patients who died in hospital (3.5 +/- 0.5 vs. 1.8 +/- 0.5 cm/s). CONCLUSION: Despite similar reduction in LV systolic function, CS patients have reduced myocardial velocities and higher filling pressures using TDI, as compared to CHF patients. Whether TDI could be a reliable tool to determine CS patients with the best chance of recovery following revascularization is yet to be determined.

Quantitative estimation of left atrial linear dimension on a transthoracic echocardiogram using an electrocardiographic formulaic assessment.

A proportionate and incremental association between left atrial (LA) dilatation on a transthoracic echocardiogram (TTE) and increasing severity in abnormal atrial depolarization can be described by the regression formula: LA dimension in parasternal long-axis view (in millimeters) = 2.47 + 0.29 [P-wave duration (in milliseconds)]. However, prospective testing of this formula for LA quantification with comparison to other TTE indexes is lacking. We prospectively obtained 12-lead electrocardiograms for 72 consecutive patients before individual, nonemergent TTE assessment. P waves were assessed independently to the nearest 10 ms for application of the formula with a Bland-Altman plot. P-wave durations were obtained specifically from lead II and also from any lead that yielded the widest measurement. There was a strong formulaic correlation with LA measurement by TTE (p <0.00000001; r = 0.662), irrespective of electrocardiographic lead used. However, as the measurement difference increased between that in any lead and lead II, correlation strength increased. Correlation was not significantly affected by commonly measured electrocardiographic and TTE indexes, such as, PR interval, QRS complex, and left ventricular end-diastolic as well as systolic dimensions, after adjustment for these variables. Moreover, when the P-wave axis remained within the normal range, the correlation strength increased. The Bland-Altman plot also showed good agreement of LA dimension assessment between formulaic estimation and TTE measurement. In conclusion, there is good agreement and correlation between formulaic estimation and that of TTE for measurement of LA linear dimension. The LA regression formula is an indirect asset that could perhaps supplement LA quantification on TTE in certain circumstances.

Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy.

OBJECTIVES: In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM). BACKGROUND: It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort. METHODS: Clinical and echocardiographic data were evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide. RESULTS: Patients were followed with disopyramide for 3.1 +/- 2.6 years; dose 432 +/- 181 mg/day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 +/- 33 to 40 +/- 32 mm Hg (p < 0.0001) and mean New York Heart Association functional class from 2.3 +/- 0.7 to 1.7 +/- 0.6 (p < 0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non-disopyramide-treated patients did not differ significantly, 1.4% versus 2.6%/year (p = 0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p = 0.08). CONCLUSIONS: Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over >/=3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.

Comparison of diastolic septal perforator flow velocities in hypertrophic cardiomyopathy versus hypertensive left ventricular hypertrophy.

In this study, we measured diastolic septal perforator flow velocities by Doppler transthoracic echocardiography (TTE) in patients with hypertrophic cardiomyopathy (HCM). Using color-guided pulsed Doppler TTE, septal perforator flow velocity recordings were attempted in 69 patients and successfully recorded in 47 (68%). First, we compared 14 patients with HCM to 12 controls and to 11 patients with hypertension with left ventricular hypertrophy. Next, in 10 additional patients with HCM, we compared the septal velocities with the epicardial left anterior descending artery (LAD) velocities recorded during the same TTE study. In the patients with HCM, the peak septal diastolic velocities were twice that of the normal controls (88 +/- 40 vs 41 +/- 13 cm/s) and also higher than in hypertensive left ventricular hypertrophy (51 +/- 18 cm/s, p < 0.0001). All 10 patients with HCM showed a step-up of peak diastolic velocity from the LAD to the septal perforator from 41 +/- 9 to 72 +/- 17 cm/s (p < 0.0001). Three patients with HCM had surgical septal myectomy. These patients had luminal narrowings of the small intramural arteries at histopathologic examination. In conclusion, pulsed Doppler measurement of septal perforator flow velocities is feasible. In HCM, the epicardial coronary arteries enlarge to accommodate increased flow, and diastolic velocity is normalized. In contrast, the increased velocities in the septal branches of patients with HCM are similar to those previously observed in tunnel-like obstructions. These findings suggest that in HCM, notwithstanding an increase in coronary flow, hemodynamically significant narrowings are present in the septal branches. Doppler TTE may become useful for evaluation of abnormal intramural coronary flow in HCM.

Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy.

OBJECTIVES: The goal of this study was to determine the impact of race on identification of hypertrophic cardiomyopathy (HCM). BACKGROUND: Sudden death in young competitive athletes is due to a variety of cardiovascular diseases (CVDs) and, most commonly, HCM. These catastrophes have become an important issue for African Americans, although HCM has been previously regarded as rare in this segment of the U.S. population. METHODS: We studied the relationship of race to the prevalence of CVDs causing sudden death in our national athlete registry, and compared these findings with a representative multicenter hospital-based cohort of patients with HCM. RESULTS: Of 584 athlete deaths, 286 were documented to be due to CVD at ages 17 +/- 3 years; 156 (55%) were white, and 120 (42%) were African American. Most were male (90%), and 67% participated in basketball and football. Among the 286 cardiovascular deaths, most were due to HCM (n = 102; 36%) or anomalous coronary artery of wrong sinus origin (n = 37; 13%). Of the athletes who died of HCM, 42 (41%) were white, but 56 (55%) were African American. In contrast, of 1,986 clinically identified HCM patients, only 158 (8%) were African American (p < 0.001). CONCLUSIONS: In this autopsy series, HCM represented a common cause of sudden death in young and previously undiagnosed African American male athletes, in sharp contrast with the infrequent clinical identification of HCM in a hospital-based population (i.e., by seven-fold). This discrepancy suggests that many HCM cases go unrecognized in the African American community, underscoring the need for enhanced clinical recognition of HCM to create the opportunity for preventive measures to be employed in high-risk patients with this complex disease.

Correlation of echocardiographic left atrial abnormality with myocardial ischemia during myocardial perfusion assessment in the presence of known left ventricular hypertrophy.

Left atrial (LA) abnormality, an easily quantifiable parameter of left ventricular (LV) diastolic dysfunction, has been associated with cardiovascular risk similar to that of LV hypertrophy. The correlation between LV hypertrophy and LA abnormality among patients undergoing myocardial perfusion (MP) study has not been described. We prospectively studied 78 consecutive patients with LV hypertrophy who underwent MP study after screening for electrocardiographic and echocardiographic LA abnormality over a 6-month period. Of those, 48 had a positive MP imaging result, and 30 did not. LA size (p = 0.002) and P-wave duration (p = 0.017) were significantly increased in the former. The differential change in LA size (no defect = 35 ± 4, mild = 36 ± 5, moderate = 38 ± 5, severe = 44 ± 5 mm; p <0.0001) and P-wave duration (no defect = 107 ± 14, mild = 110 ± 17, moderate = 113 ± 15, severe = 127 ± 22 ms; p = 0.003) was greatest when the MP study defect exceeded moderate severity. In conclusion, the presence of LA abnormality could assist during MP study interpretation among patients with LV hypertrophy when such markers appear to be correlated with the severity of the MP study defect.

Role of three-dimensional echocardiography in breast cancer: comparison with two-dimensional echocardiography, multiple-gated acquisition scans, and cardiac magnetic resonance imaging.

PURPOSE: In patients with breast cancer, the administration of doxorubicin and trastuzumab is associated with an increased risk of cardiotoxicity. Although multiple-gated acquisition (MUGA) scans and two-dimensional transthoracic echocardiography (TTE) are conventional methods for baseline and serial assessment of left ventricular ejection fraction (LVEF) in these patients, little is known about the use of real-time three-dimensional TTE (RT3D TTE) in this clinical setting. The aim of this study was to assess the accuracy of MUGA, 2D TTE, and RT3D TTE for determining LVEF in comparison to cardiac magnetic resonance imaging (CMR). METHODS: Between 2007 and 2009 inclusive, 50 female patients with human epidermal growth factor receptor 2-positive breast cancer received adjuvant trastuzumab after doxorubicin. Serial MUGA, 2D TTE, RT3D TTE, and CMR were performed at baseline, 6, and 12 months after the initiation of trastuzumab. RESULTS: A comparison of left ventricular end diastolic volume (LVEDV) demonstrated a modest correlation between 2D TTE and CMR (r = 0.64 at baseline; r = 0.69 at 12 months, respectively). A comparison of LVEDV between RT3D TTE and CMR demonstrated a stronger correlation (r = 0.87 at baseline; r = 0.95 at 12 months, respectively). Although 2D TTE demonstrated a weak correlation with CMR for LVEF assessment (r = 0.31 at baseline, r = 0.42 at 12 months, respectively), both RT3D TTE and MUGA showed a strong correlation when compared with CMR (r = 0.91 at baseline; r = 0.90 at 12 months, respectively). CONCLUSION: As compared with conventional MUGA, RT3D TTE is a feasible, accurate, and reproducible alternate imaging modality for the serial monitoring of LVEF in patients with breast cancer.

Forgotten but not extinct: lessons in hemodynamics and imaging from pancardiac rheumatic heart disease.

Simultaneous valvular, pericardial and myocardial involvement from chronic rheumatic heart disease is a rare phenomenon. We describe a novel patient with simultaneous aortic stenosis, mitral stenosis, constrictive pericarditis and pathologic myocardial rheumatic involvement. Lessons and pitfalls of the catheterization hemodynamics for concomitant multivalvular disease and constrictive physiology are outlined. Echocardiographic, computed tomographic (CT) imaging and pathologic findings are presented for the pancardiac involvement in this case.

Effect of obstruction on longitudinal left ventricular shortening in hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the cause of the midsystolic drop (MSD) in left ventricular (LV) ejection velocities that are observed with hypertrophic cardiomyopathy (HCM) and severe obstruction. BACKGROUND: Dynamic obstruction is an important determinant of symptoms and adverse outcome. The MSD in velocity and flow occurs in patients with gradients >60 mm Hg. The nadir velocity in the LV occurs simultaneously with peak gradient. METHODS: We studied 36 patients with obstructive HCM and an MSD and compared them with 15 patients with HCM and no obstruction and with 25 age-matched normal control subjects. We measured LV ejection velocity proximal and distal to LV obstruction as well as tissue Doppler velocities and time intervals. RESULTS: The duration of contraction of both the septum and lateral wall is shorter in obstructed patients with the MSD than in nonobstructed HCM patients: septal contraction 203 +/- 68 ms vs. 271 +/- 41 ms (p < 0.001). Parallel reduction in the length of shortening was noted: 1.2 +/- 0.6 cm vs. 1.9 +/- 0.4 cm (p < 0.001). The ejection velocity nadir follows the septal and lateral peak velocities by 100 ms and 60 ms, respectively. The velocity nadir occurs as both walls rapidly decelerate to their premature termination: septal deceleration 79 +/- 35 cm/s2 vs. 48 +/- 21 cm/s2 (p < 0.001). With medical abolition of obstruction the MSD disappears and the duration and length of contraction normalizes. CONCLUSIONS: These data indicate that the MSD is caused by premature termination of LV segmental shortening and is a manifestation of systolic dysfunction.