Anthony N. DeMaria

Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms.

We have presented recommendations for the optimum acquisition of quantitative two-dimensional data in the current echocardiographic environment. It is likely that advances in imaging may enhance or supplement these approaches. For example, three-dimensional reconstruction methods may greatly augment the accuracy of volume determination if they become more efficient. The development of three-dimensional methods will depend in turn on vastly improved transthoracic resolution similar to that now obtainable by transesophageal echocardiography. Better resolution will also make the use of more direct methods of measuring myocardial mass practical. For example, if the epicardium were well resolved in the long-axis apical views, the myocardial shell volume could be measured directly by the biplane method of discs rather than extrapolating myocardial thickness from a single short-axis view. At present, it is our opinion that current technology justifies the clinical use of the quantitative two-dimensional methods described in this article. When technically feasible, and if resources permit, we recommend the routine reporting of left ventricular ejection fraction, diastolic volume, mass, and wall motion score.

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of Intravenous Adult Human Mesenchymal Stem Cells (Prochymal) After Acute Myocardial Infarction

OBJECTIVES Our aim was to investigate the safety and efficacy of intravenous allogeneic human mesenchymal stem cells (hMSCs) in patients with myocardial infarction (MI). BACKGROUND Bone marrow-derived hMSCs may ameliorate consequences of MI, and have the advantages of preparation ease, allogeneic use due to immunoprivilege, capacity to home to injured tissue, and extensive pre-clinical support. METHODS We performed a double-blind, placebo-controlled, dose-ranging (0.5, 1.6, and 5 million cells/kg) safety trial of intravenous allogeneic hMSCs (Prochymal, Osiris Therapeutics, Inc., Baltimore, Maryland) in reperfused MI patients (n=53). The primary end point was incidence of treatment-emergent adverse events within 6 months. Ejection fraction and left ventricular volumes determined by echocardiography and magnetic resonance imaging were exploratory efficacy end points. RESULTS Adverse event rates were similar between the hMSC-treated (5.3 per patient) and placebo-treated (7.0 per patient) groups, and renal, hepatic, and hematologic laboratory indexes were not different. Ambulatory electrocardiogram monitoring demonstrated reduced ventricular tachycardia episodes (p=0.025), and pulmonary function testing demonstrated improved forced expiratory volume in 1 s (p=0.003) in the hMSC-treated patients. Global symptom score in all patients (p=0.027) and ejection fraction in the important subset of anterior MI patients were both significantly better in hMSCs versus placebo subjects. In the cardiac magnetic resonance imaging substudy, hMSC treatment, but not placebo, increased left ventricular ejection fraction and led to reverse remodeling. CONCLUSIONS Intravenous allogeneic hMSCs are safe in patients after acute MI. This trial provides pivotal safety and provisional efficacy data for an allogeneic bone marrow-derived stem cell in post-infarction patients. (Safety Study of Adult Mesenchymal Stem Cells [MSC] to Treat Acute Myocardial Infarction; NCT00114452).

Utility of B-Natriuretic Peptide in Detecting Diastolic Dysfunction Comparison With Doppler Velocity Recordings

Background—Although Doppler echocardiography has been used to identify abnormal left ventricular (LV) diastolic filling dynamics, inherent limitations suggest the need for additional measures of diastolic dysfunction. Because data suggest that B-natriuretic peptide (BNP) partially reflects ventricular pressure, we hypothesized that BNP levels could predict diastolic abnormalities in patients with normal systolic function. Methods and Results—We studied 294 patients referred for echocardiography to evaluate ventricular function. Patients with abnormal systolic function were excluded. Cardiologists making the assessment of LV function were blinded to BNP levels. Patients were classified as normal, impaired relaxation, pseudonormal, and restrictivelike filling patterns. Patients diagnosed with evidence of abnormal LV diastolic function (n=119) had a mean BNP concentration of 286±31 pg/mL; those in the normal LV group (n=175) had a mean BNP concentration of 33±3 pg/mL. Patients with restrictivelike filling patterns on echocardiography had the highest BNP levels (408±66 pg/mL), and patients with symptoms had higher BNP levels in all diastolic filling patterns. The area under the receiver-operating characteristic curve for BNP to detect any diastolic dysfunction was 0.92 (95% CI, 0.87 to 0.95;P <0.001). A BNP value of 62 pg/mL had a sensitivity of 85%, a specificity of 83%, and an accuracy of 84% for detecting diastolic dysfunction. Conclusions—A rapid assay for BNP can reliably detect the presence of diastolic abnormalities on echocardiography. In patients with normal systolic function, elevated BNP levels and diastolic filling abnormalities might help to reinforce the diagnosis diastolic dysfunction.

Utility of B-Natriuretic Peptide in Detecting Diastolic Dysfunction

Background— Although Doppler echocardiography has been used to identify abnormal left ventricular (LV) diastolic filling dynamics, inherent limitations suggest the need for additional measures of diastolic dysfunction. Because data suggest that B-natriuretic peptide (BNP) partially reflects ventricular pressure, we hypothesized that BNP levels could predict diastolic abnormalities in patients with normal systolic function. Methods and Results— We studied 294 patients referred for echocardiography to evaluate ventricular function. Patients with abnormal systolic function were excluded. Cardiologists making the assessment of LV function were blinded to BNP levels. Patients were classified as normal, impaired relaxation, pseudonormal, and restrictivelike filling patterns. Patients diagnosed with evidence of abnormal LV diastolic function (n=119) had a mean BNP concentration of 286±31 pg/mL; those in the normal LV group (n=175) had a mean BNP concentration of 33±3 pg/mL. Patients with restrictivelike filling ...

State of the art: using natriuretic peptide levels in clinical practice

Natriuretic peptide (NP) levels (B‐type natriuretic peptide (BNP) and N‐terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state‐of‐the‐art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians:

Utility of B-natriuretic peptide levels in identifying patients with left ventricular systolic or diastolic dysfunction

Abstract Purpose Although echocardiography is important for making the diagnosis of left ventricular dysfunction, its cost and lack of availability limit its use as a routine screening test. B-Natriuretic peptide levels accurately reflect ventricular pressure, and preliminary studies with a rapid assay have found that levels are sensitive and specific for diagnosing heart failure in patients with dyspnea. We hypothesized that B-natriuretic peptide levels obtained through the use of a rapid assay should correlate with echocardiographic abnormalities of ventricular function. Subjects and methods We studied 400 patients who were referred for echocardiography at the San Diego Veterans Healthcare System between June and August 2000 to evaluate ventricular function. B-natriuretic peptide levels were measured by a point-of-care immunoassay; cardiologists assessing left ventricular function were blinded to the assay results. Patients were grouped into those with normal ventricular function, systolic dysfunction only, diastolic dysfunction only, and both systolic and diastolic dysfunction. Results Mean (± SD) B-natriuretic peptide concentration was 416 ± 413 pg/mL in the 253 patients diagnosed with abnormal left ventricular function, compared with 30 ± 36 pg/mL in the 147 patients with normal left ventricular function. Patients with both systolic and diastolic dysfunction had the highest levels (675 ± 423 pg/mL). The area under the receiver operating characteristic (ROC) curve for B-natriuretic peptide levels to detect any abnormal echocardiographic finding was 0.95 (91% confidence interval: 0.93 to 0.97). B-Natriuretic peptide levels were unable to differentiate systolic vs. diastolic dysfunction. In patients with symptoms of heart failure and normal systolic function, B-natriuretic peptide levels >57 pg/mL had a positive predictive value of 100% for diastolic abnormalities. Conclusions A simple, rapid test for B-natriuretic peptide levels can reliably predict the presence or absence of left ventricular dysfunction on echocardiogram. For some patients, a normal level may preclude the need for echocardiography.

Contraction and Relaxation Velocities of the Normal Left Ventricle Using Pulsed-Wave Tissue Doppler Echocardiography

We designed the present study (1) to investigate the velocities of longitudinal movement of the human left ventricle by pulsed-wave tissue Doppler (PWTD) imaging; (2) to test the hypothesis that a heterogeneous pattern of longitudinal systolic and diastolic velocities exists among individual left ventricular wall segments; (3) to establish the range of this heterogeneity, and (4) to correlate the function of individual segments with the known orientation of myocardial fibers. PWTD is a novel ultrasound method to quantify myocardial contraction and relaxation velocities. In 27 young normal subjects, PWTD peak values of longitudinal systolic and diastolic velocities were measured for 12 left ventricular segments visualized from the apical window. The PWTD sampling of each myocardial segment resulted in a triphasic velocity curve during each cardiac cycle: a systolic velocity wave (S) directed toward the transducer, and an early diastolic (E) and a late diastolic (A) velocity wave away from the transducer. A heterogeneous pattern of systolic and diastolic myocardial velocities was observed between individual wall segments as well as for the basal and midsegments of each myocardial wall. The difference between the highest and lowest values for S was 38.4% in the basal segments and 56.3% in the midwall segments. The difference between low and high velocities for E was 61.4% in the basal and 38.2% in the midsegments; for A the difference was 29.5% in the basal and 32.6% in the midsegments. In general, lower velocity values were found in the septum with higher basal to midwall difference. The lateral and posterior walls had higher, but more uniform, velocities. PWTD enables the quantitative assessment of regional systolic and diastolic myocardial velocities. Substantial heterogeneity of velocities exists within individual myocardial segments, and must be taken into account in any clinical application. The observed heterogeneity in longitudinal function is consistent with the known spatial distribution of myocardial fibers.

Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction

A hydrogel derived from myocardial extracellular matrix mitigates negative left ventricular remodeling and improves heart function after myocardial infarction in pigs. Healing Biomaterial Delivered to Heart Repairing a broken heart takes more than just time—it may also take a special hydrogel material derived from the heart itself. After a heart attack, cells die and are replaced by a thick scar, which cannot pump blood like normal tissue. This results in total heart failure and death in these patients that survive the initial heart attack. In response, Seif-Naraghi and colleagues have developed a biomaterial that can be injected into the heart to prevent scar formation and help the heart to heal and function as it normally would. The authors used a pig model to study the effects of a myocardial extracellular matrix (ECM)–derived biomaterial on heart healing after myocardial infarction (MI). Two weeks after MI, the material was delivered via catheter to the target region of the heart—much like it would in a real clinical trial with patients. Control animals received either no injection or saline only. After 3 months, tests were performed to see if the heart had healed, if it functioned properly, and if the material caused any irritation to the heart tissue. Seif-Naraghi et al. reported improvements in heart function in the matrix-injected animals and worsening of function in the controls. Their data suggest that the matrix can prevent post-MI negative left ventricular remodeling by improving systolic function and contractility. Other than function, the material appeared to encourage healthy muscle and blood vessel formation in the infarcted areas, whereas tissue from control animals was thin and fibrotic. This myocardial matrix material did not damage peripheral tissues, such as the lungs and liver, or disrupt cardiac rhythm in pigs. Even with direct injection into the left ventricle lumen in rats, there was no inflammation, edema, or hemorrhage. These data in a large animal show that the myocardial ECM–derived material not only improves functional outcome after a heart attack but also is safe and nontoxic, thus making the material ready to move forward toward clinical tests in people. New therapies are needed to prevent heart failure after myocardial infarction (MI). As experimental treatment strategies for MI approach translation, safety and efficacy must be established in relevant animal models that mimic the clinical situation. We have developed an injectable hydrogel derived from porcine myocardial extracellular matrix as a scaffold for cardiac repair after MI. We establish the safety and efficacy of this injectable biomaterial in large- and small-animal studies that simulate the clinical setting. Infarcted pigs were treated with percutaneous transendocardial injections of the myocardial matrix hydrogel 2 weeks after MI and evaluated after 3 months. Echocardiography indicated improvement in cardiac function, ventricular volumes, and global wall motion scores. Furthermore, a significantly larger zone of cardiac muscle was found at the endocardium in matrix-injected pigs compared to controls. In rats, we establish the safety of this biomaterial and explore the host response via direct injection into the left ventricular lumen and in an inflammation study, both of which support the biocompatibility of this material. Hemocompatibility studies with human blood indicate that exposure to the material at relevant concentrations does not affect clotting times or platelet activation. This work therefore provides a strong platform to move forward in clinical studies with this cardiac-specific biomaterial that can be delivered by catheter.

Accuracy of echocardiography versus electrocardiography in detecting left ventricular hypertrophy: Comparison with postmortem mass measurements

The accuracy of electrocardiography, M-mode echocardiography and two-dimensional echocardiography in predicting left ventricular hypertrophy was compared in 50 patients who came to autopsy within 6 months after the studies were performed. Several methods for determining left ventricular hypertrophy were examined for each of the three techniques. M-mode echocardiography was technically adequate to evaluate the presence or absence of left ventricular hypertrophy more often than either electrocardiography or two-dimensional echocardiography. Measurements from M-mode echocardiography also correlated best with autopsy measurements. Both echocardiographic techniques had a higher sensitivity than electrocardiographic criteria in diagnosing left ventricular hypertrophy. Two-dimensional echocardiography was not shown to improve the M-mode assessment of left ventricular hypertrophy. In an attempt to simplify both M-mode left ventricular mass calculations and the diagnosis of left ventricular hypertrophy for the clinician, a left ventricular mass nomogram was constructed, enabling quick insertion of standard M-mode echocardiographic measurements.

The Variable Spectrum of Echocardiographic Manifestations of the Mitral Valve Prolapse Syndrome

The variety of echographic features associated with the mitral valve prolapse syndrome (MVPS) is not yet completely understood. Therefore, ultrasound recordings were obtained in 33 patients in whom mitral prolapse had been documented by biplane left ventricular cineangiography. Echographic abnormailities of the mitral leaflets during systole were recorded in 26/27 MVPS patients and 6/6 with ruptured chordae tendineae. In MVPS, the midsystolic mitral buckling, emphasized in early echocardiographic studies, was observed in only 12 patients. In our study, the most common aberrancy was abnormal pansystolic mitral motion in 14 patients, which in 12 was similar to the pansystolic bowing observed in all six patients with torn chordae. An additional echographic abnormality in MVPS was localized mitral collapse throughout systole in 10/14 patients with pansystolic prolapse; this finding was the most striking defect noted in five, in two of whom it was the only disturbance. Phonocardiography in MVPS showed typical midsystolic click and/or late systolic murmur in only 15/26 patients of whom ten had midsystolic mitral buckling. A variety of systolic clicks and/or murmurs occurred in the 14 patients with generalized bowing and/or localized collapse throughout systole on echocardiography. Thus, the mitral echographic spectrum of MVPS is comprised of three different abnormal patterns of systolic prolapse: buckling in midsystole, pansystolic bowing, and pansystolic collapse. These echocardiographic disorders commonly occur in the absence of classical auscultatory findings in MVPS and the most frequent abnormality on ultrasound is pansystolic bowing of both mitral leaflets.