Interventional magnetic resonance imaging for guiding gene and cell transfer in the heart.

BACKGROUND: Interventional magnetic resonance imaging (iMRI) has the potential for guiding interventional cardiac procedures in real time. OBJECTIVES: To test the feasibility of iMRI guided gene and cell transfer to the heart and to monitor myocardial remodelling after myocardial infarction in a rat model. METHODS: The MRI contrast agent GdDTPA, together with either Evans blue dye, or a recombinant adenovirus encoding the LacZ gene, or primary fibroblasts tagged by BrdU, were injected into the myocardium of rats under iMRI guidance. Rats were killed seven days after the injection and the hearts sectioned to identify the blue dye, LacZ expression, or fibroblast presence, respectively. In a parallel study, left ventricular area was measured before and after myocardial infarction and in sham operated rats by T1 weighted MRI and by echocardiography. RESULTS: Location of GdDTPA enhancement observed with iMRI at the time of injection was correlated with Evans blue stain, beta-gal expression, and the primary fibroblast location in histological studies. iMRI and echocardiography measured a comparable increase in left ventricular area at seven and 30 days after myocardial infarction. A good correlation was found between the iMRI and echocardiographic assessment of left ventricular area (r = 0.70; p < 0.0001) and change in left ventricular area with time (r = 0.75; p < 0.0001). CONCLUSIONS: The results show the feasibility and efficiency of iMRI guided intramyocardial injections, and the ability to monitor heart remodelling using iMRI. Genes, proteins, or cells for tissue engineering could be injected accurately into the myocardial scar under iMRI guidance.

Dobutamine echocardiography in patients with aortic stenosis and left ventricular dysfunction: predicting outcome as a function of management strategy.

STUDY OBJECTIVE: To prospectively address the question whether the assessment of valvular hemodynamics and myocardial function during low-dose dobutamine infusion can guide decision making in patients with aortic stenosis and left ventricular (LV) dysfunction. PATIENTS AND MEASUREMENTS: Twenty-four patients with aortic stenosis and LV dysfunction (mean ejection fraction, 28%; New York Heart Association class, II to IV) were studied by dobutamine echocardiography assessing mean pressure gradient, aortic valve area, and aortic valve resistance. Patients were prospectively divided into severe and nonsevere aortic stenosis groups according to the response of the valve area to the augmentation of systolic flow. The clinical decision was considered to be concordant with the results of dobutamine echocardiography, when patients with severe aortic stenosis and preserved contractile function were referred by a specialist for aortic valve replacement and when patients with nonsevere aortic stenosis were not. Patients were observed for up to 3 years. RESULTS: All eight patients with severe aortic stenosis who were referred for surgery survived and had good cardiovascular outcomes, and six of eight patients who were not initially referred for surgery had poor outcomes, including heart failure and sudden cardiac death. The eight patients with nonsevere aortic stenosis did comparatively well without valve replacement. Cardiac death or pulmonary edema occurred in 4 of 16 patients (25%) when the clinical decision was concordant with the results of the dobutamine echocardiogram and occurred in 6 of 8 patients (75%) when the clinical decision was discordant (p = 0.019 [chi(2) test]). CONCLUSION: Patients with aortic stenosis, LV dysfunction, and relatively low gradients have better outcomes when management decisions are based on the results of dobutamine echocardiograms. Those patients identified as having severe aortic stenosis and preserved contractile reserve by dobutamine echocardiography should undergo surgery, while patients identified as having nonsevere aortic stenosis can be managed conservatively.

Impact of atrioventricular compliance on pulmonary artery pressure in mitral stenosis: an exercise echocardiographic study.

BACKGROUND: The decay of the pressure gradient across a stenotic mitral valve is determined by the size of the orifice and net AV compliance (C(n)). We have observed a group of symptomatic patients, usually in sinus rhythm, characterized by pulmonary hypertension (particularly during exercise) despite a relatively large mitral valve area by pressure half-time. We speculated that this discrepancy was due to low atrial compliance causing both pulmonary hypertension and a steep decay of the transmitral pressure gradient despite significant stenosis. We therefore tested the hypothesis that C(n) is an important physiological determinant of pulmonary artery pressure at rest and during exercise in mitral stenosis. METHODS AND RESULTS: Twenty patients with mitral stenosis were examined by Doppler echocardiography. C(n), calculated from the ratio of effective mitral valve area (continuity equation) and the E-wave downslope, ranged from 1.7 to 8.1 mL/mm Hg. Systolic pulmonary artery pressure (PAP) increased from 43+/-12 mm Hg at rest to 71+/-23 mm Hg (range, 40 to 110 mm Hg) during exercise. There was a particularly close correlation between C(n) and exercise PAP (r=-0.85). Patients with a low compliance were more symptomatic (P<0.025). Catheter- and Doppler-derived values for C(n), determined in 10 cases, correlated well (r=0.79). CONCLUSIONS: C(n), which can be noninvasively assessed, is an important physiological determinant of PAP in mitral stenosis. Patients with low C(n) represent an important clinical entity, with symptoms corresponding to severe increases in PAP during stress echocardiography.

Echocardiography can detect cloth cover tears in fully covered Starr-Edwards valves: a long-term clinical and echocardiographic study.

The incidence of cloth cover tears in fully covered Starr-Edwards valves, as assessed by autopsy or repeat surgery, is approximately 1% per patient-year. However, no echocardiographic study has explored this phenomenon. This study was designed as a one-time observational study and aimed to explore the ability of two-dimensional transthoracic echocardiography to identify cloth cover tears in 35 late survivors with 38 fully covered Starr-Edwards valves who had been operated on 20 to 24 years earlier. The hemodynamic profile, clinical status, and valve-related complications in this highly selected group of late survivors were also studied. Five patients also underwent transesophageal echocardiography. An elongated echogenic mass attached to the prosthetic valve cage and floating downstream was considered indicative of cloth tear. There were 16 patients with aortic valve prostheses, 16 with mitral valve prostheses, and three with double prosthetic valves. In six (17.1%) patients (four with aortic valve prostheses, two with mitral valve prostheses), an echogenic mass suggestive of cloth cover tear was detected, which was confirmed by transesophageal echocardiography in three patients. In two patients the echocardiographic finding was confirmed at surgery. The initial presentation of these six patients was endocarditis, possible embolism, unexplained dyspnea, and weakness in one patient each. Two patients were asymptomatic. There was no evidence of significant prosthetic valve malfunction in any patient. The transvalvular gradients were similar in patients with and without cloth cover tears. Echocardiographic findings highly suggestive of cloth cover tears are not uncommon and can be detected in the third postoperative decade in patients with fully covered Starr-Edwards valves. A prospective study to evaluate the clinical significance of an incidental echocardiographic finding suggestive of cloth cover tears in asymptomatic patients with these valve models is warranted.

Primary coronary artery bypass grafting without cardiopulmonary bypass in impaired left ventricular function.

BACKGROUND: Conventional coronary artery bypass grafting using cardiopulmonary bypass carries relatively high mortality and morbidity for patients with left ventricular dysfunction. METHODS: Seventy-five patients with ejection fraction less than or equal to 0.35 underwent primary coronary artery bypass grafting without cardiopulmonary bypass between December 1991 and December 1994. Thirty-two patients (43%) had congestive heart failure, 11 (15%) were referred for operation within the first 24 hours of evolving myocardial infarction, and 21 (28%) up to 1 week after acute myocardial infarction. Eighteen patients (24%), 6 of whom were in cardiogenic shock, underwent emergency operations. RESULTS: Mean number of grafts/patient was 1.9 (range, 1 to 4), and internal mammary artery was used in 66 patients (85%). Only 17 patients (23%) received a graft to a circumflex marginal artery. Two patients (2.7%) died perioperatively, and 1 (1.3%) sustained stroke. At mean follow-up of 28 months, 13 patients had died, and angina had returned in 7 (10.5%). One- and four-year actuarial survival was 96% and 73%, respectively. CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass is a viable alternative to conventional coronary artery bypass grafting particularly for patients with extreme left ventricular dysfunction or those with coexisting risk factors, such as acute myocardial infarction and cardiogenic shock.

Multiplane transesophageal echocardiographic doppler imaging accurately determines cardiac output measurements in critically ill patients.

OBJECTIVES: To compare cardiac output and stroke volume measured by multiplane transesophageal Doppler echocardiography with that measured by the thermodilution technique. DESIGN: Prospective direct comparison of paired measurements by both techniques in each patient. SETTING: Cardiac surgery and myocardial infarction intensive care units. PATIENTS: Twenty-nine patients, mean age (+/- SD) 67 +/- 8 years. Nineteen had undergone open heart surgery and 10 had suffered acute myocardial infarction. METHODS: Cardiac output and stroke volume were measured simultaneously by the thermodilution technique and multiplane transesophageal Doppler echocardiography via the transgastric view (119 +/- 8 degrees) with the sample volume positioned at the level of the left ventricular outflow tract. RESULTS: Stroke volume and cardiac output measurements were obtained in 29 of 33 patients (88%). Mean values were 50 +/- 13 mL and 4.8 +/- 1.3 L/min by Doppler and 51 +/- 14 mL and 4.9 +/- 1.4 L/min by thermodilution (r = 0.90, r = 0.91, p < 0.001). The mean differences in values obtained with the two techniques were 1 +/- 6 mL (2 +/- 12%) and 0.1 +/- 0.7 L/min (2 +/- 12%). CONCLUSIONS: Multiplane transesophageal echocardiography enhances the ability to estimate accurately cardiac output and stroke volume by providing new access to left ventricular outflow tract in critically ill patients.