Eddy Barasch

Myocardial Revascularization With Laser Preliminary Findings

BACKGROUND We assessed the transmyocardial laser revascularization (TMLR) as sole therapy in patients with symptomatic coronary artery disease refractory to interventional or medical treatment. METHODS AND RESULTS Thirty-one patients were evaluated with positron emission tomography (PET), dobutamine echocardiography, 201Tl single-photon emission computed tomography (201Tl-SPECT), and multigated acquisition radionuclide ventriculography (MUGA). TMLR was performed in 21 patients who had demonstrable ischemia in viable myocardium. The mean Canadian Cardiovascular Society (CCS) angina class was 3.70 +/- 0.7 (4 patients with unstable angina). Untreated septal segments were used as controls. At 3 months, (n = 15 patients), the mean CCS angina class was to 2.43 +/- 0.9 (P < .05). On dobutamine echocardiography, the mean resting wall motion score index was improved by 16% in lased segments (P < .03 vs control), and mean LVEF at peak stress increased by 19% (P = NS vs baseline). On 201Tl-SPECT, perfusion of lased and nonlased segments did not change. On PET, the mean ratio of subendocardial to subepicardial perfusion (SEn/SEp) increased 14% over baseline (P < .001 vs control). At 6 months (n = 15 patients), the mean CCS angina class was 1.7 +/- 0.8 (P < .05). The mean resting wall motion score index was up by 13% in lased segments (P < .05 vs control). Resting LVEF was unchanged. Stress LVEF increased 21% (P = NS vs baseline). Myocardial perfusion remained unchanged by 201Tl-SPECT. On PET, 36% of the lased segments were better, and 25% were worse compared with baseline. The resting SEn/SEp by PET was up 21% (P < .001 vs control). All deaths (two perioperative and three late) occurred in patients with preoperative congestive heart failure. Two patients required repeat revascularization of new coronary lesions. CONCLUSIONS These results suggest that TMLR improves anginal status, relative endocardial perfusion, and cardiac function in patients who do not have preoperative congestive heart failure.

Relative Importance of Errors in Left Ventricular Quantitation by Two-Dimensional Echocardiography: Insights From Three-Dimensional Echocardiography and Cardiac Magnetic Resonance Imaging

BACKGROUND The accuracy of left ventricular (LV) volumes and ejection fraction (EF) on two-dimensional echocardiography (2DE) is limited by image position (IP), geometric assumption (GA), and boundary tracing (BT) errors. METHODS Real-time three-dimensional echocardiography (RT3DE) and cardiac magnetic resonance imaging (CMR) were used to determine the relative contribution of each error source in normal controls (n = 35) and patients with myocardial infarctions (MIs) (n = 34). LV volumes and EFs were calculated using (1) apical biplane disk summation on 2DE (IP + GA + BT errors), (2) biplane disk summation on RT3DE (GA + BT errors), (3) 4-multiplane to 8-multiplane surface approximation on RT3DE (GA + BT errors), (4) voxel-based surface approximation on RT3DE (BT error alone) and (5) CMR. By comparing each method with CMR, the absolute and relative contributions of each error source were determined. RESULTS IP error predominated in LV volume quantification on 2DE in normal controls, whereas GA error predominated in patients with MIs. Underestimation of volumes on 2DE was overcome by increasing the number of imaging planes on RT3DE. Although 4 equidistant image planes were acceptable, the best results were achieved with voxel-based RT3DE. For EF estimation, IP error predominated in normal controls, whereas BT error predominated in patients with MIs. Nevertheless, one third of the EF estimation error in patients with MIs was due to a combination of IP and GA errors, both of which may be addressed using RT3DE. CONCLUSIONS The relative contribution of each source of LV quantitation error on 2DE was defined and quantified. Each source of error differed depending on patient characteristics and LV geometry.

Association of serum phosphate levels with aortic valve sclerosis and annular calcification: the cardiovascular health study.

OBJECTIVES This study was conducted to evaluate mineral metabolism markers as potential risk factors for calcific aortic valve disease. BACKGROUND Mineral metabolism disturbances are common among older people and may contribute to cardiac valvular calcification. Associations of serum mineral metabolism markers with cardiac valvular calcification have not been evaluated in a well-characterized general population of older adults. METHODS We measured serum levels of phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D in 1,938 Cardiovascular Health Study participants who were free of clinical cardiovascular disease and who underwent echocardiographic measurements of aortic valve sclerosis (AVS), mitral annular calcification (MAC), and aortic annular calcification (AAC). We used logistic regression models to estimate associations of mineral metabolism markers with AVS, MAC, and AAC after adjustment for relevant confounding variables, including kidney function. RESULTS The respective prevalences of AVS, MAC, and AAC were 54%, 39%, and 44%. Each 0.5 mg/dl higher serum phosphate concentration was associated with greater adjusted odds of AVS (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.04 to 1.31, p = 0.01), MAC (OR: 1.12, 95% CI: 1.00 to 1.26, p = 0.05), and AAC (OR: 1.12, 95% CI: 0.99 to 1.25, p = 0.05). In contrast, serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations were not associated with aortic or mitral calcification. CONCLUSIONS Higher serum phosphate levels within the normal range were associated with valvular and annular calcification in a community-based cohort of older adults. Phosphate may be a novel risk factor for calcific aortic valve disease and warrants further study.

Association Between Elevated Fibrosis Markers and Heart Failure in the Elderly The Cardiovascular Health Study

Background—Myocardial fibrosis reflects excess collagen deposition in the extracellular left ventricular matrix, which has been associated with heart failure (HF). No studies have addressed the relation between fibrosis biomarkers and HF in the elderly. Methods and Results—Serum fibrosis markers were measured in 880 participants of the Cardiovascular Health Study (mean age 77±6 years, 48% women). Participants with systolic HF (n=131, left ventricular ejection fraction <55%) and those with diastolic HF (n=179, left ventricular ejection fraction ≥55%) were compared with controls (280 with cardiovascular risk factors, and 279 healthy individuals) using a nested case-control design. Fibrosis markers included carboxyl-terminal peptide of procollagen type I, carboxyl-terminal telopeptide of collagen type I, and amino-terminal peptide of procollagen type III. Echocardiography was used to document systolic and diastolic function parameters. Analysis of variance and logistic regression analysis (per tertile odds ratios [OR]), adjusted by age, gender, race, hypertension, atrial fibrillation, coronary heart disease, baseline serum glucose, serum cystatin C, serum creatinine, C-reactive protein, any angiotensin-converting enzyme inhibitor, spironolactone or any diuretic, NT-proBNP, and total bone mineral density were performed. Systolic HF was associated with significantly elevated carboxyl-terminal telopeptide of collagen type I (OR=2.6; 95% CI=1.2 to 5.7) and amino-terminal peptide of procollagen type III (OR=3.3; 95% CI=1.6 to 5.8), when adjusting for covariates. Associations of diastolic HF were significant for carboxyl-terminal telopeptide of collagen type I (OR=3.9; 95% CI=1.9 to 8.3) and amino-terminal peptide of procollagen type III (OR=2.7; 95% CI=1.4 to 5.4). HF was not associated with elevated carboxyl-terminal peptide of procollagen type I (P>0.10), and fibrosis markers did not significantly differ between HF with diastolic versus those with systolic dysfunction (P>0.10) whereas NT-proBNP mean values were higher in systolic heart failure than in diastolic heart failure (P<0.0001). Conclusions—Fibrosis markers are significantly elevated in elderly individuals with diastolic or systolic HF. These associations remained significant when adjusting for covariates relevant to the aging process.

Interrogation of the Tricuspid Annulus by Doppler Tissue Imaging in Patients with Chronic Pulmonary Hypertension: Implications for the Assessment of Right-Ventricular Systolic and Diastolic Function

Background: Chronic pulmonary hypertension (CPHT) has a great impact on both right-ventricular (RV) systolic and diastolic properties and the assessment of those properties is not always feasible by traditional echocardiographic examination. Doppler tissue imaging (DTI) interrogation of the tricuspid annulus (TA) identifies the pattern of TA motion (TAM) and can help to assess RV function when other methods are not feasible. Aims: To determine RV systolic and diastolic function in patients with CPHT using DTI parameters of the TA. Methods: Eighty-seven patients with CPHT and 90 normal controls were studied. DTI parameters were measured including early diastolic, late diastolic and systolic velocities and time velocity integrals (TVI) of the TAM at both its lateral and medial aspect. Results: Early diastolic and systolic velocities, the ratio of early to late diastolic velocities and TVI of TAM at both lateral and medial aspects were significantly decreased in patients with CPHT compared to controls. No significant differences were seen in late diastolic velocities and TVI in both groups. Systolic velocity of the TAM at both its lateral and medial aspects significantly correlated with RV systolic function as measured by fractional RV area change. Conclusions: DTI of the TAM can be used to assess RV systolic and diastolic properties in patients with CPHT.

Association Between Elevated Fibrosis Markers and Heart Failure in the ElderlyCLINICAL PERSPECTIVE

Background—Myocardial fibrosis reflects excess collagen deposition in the extracellular left ventricular matrix, which has been associated with heart failure (HF). No studies have addressed the relation between fibrosis biomarkers and HF in the elderly. Methods and Results—Serum fibrosis markers were measured in 880 participants of the Cardiovascular Health Study (mean age 77±6 years, 48% women). Participants with systolic HF (n=131, left ventricular ejection fraction <55%) and those with diastolic HF (n=179, left ventricular ejection fraction ≥55%) were compared with controls (280 with cardiovascular risk factors, and 279 healthy individuals) using a nested case-control design. Fibrosis markers included carboxyl-terminal peptide of procollagen type I, carboxyl-terminal telopeptide of collagen type I, and amino-terminal peptide of procollagen type III. Echocardiography was used to document systolic and diastolic function parameters. Analysis of variance and logistic regression analysis (per tertile odds ratios [OR]), adjusted by age, gender, race, hypertension, atrial fibrillation, coronary heart disease, baseline serum glucose, serum cystatin C, serum creatinine, C-reactive protein, any angiotensin-converting enzyme inhibitor, spironolactone or any diuretic, NT-proBNP, and total bone mineral density were performed. Systolic HF was associated with significantly elevated carboxyl-terminal telopeptide of collagen type I (OR=2.6; 95% CI=1.2 to 5.7) and amino-terminal peptide of procollagen type III (OR=3.3; 95% CI=1.6 to 5.8), when adjusting for covariates. Associations of diastolic HF were significant for carboxyl-terminal telopeptide of collagen type I (OR=3.9; 95% CI=1.9 to 8.3) and amino-terminal peptide of procollagen type III (OR=2.7; 95% CI=1.4 to 5.4). HF was not associated with elevated carboxyl-terminal peptide of procollagen type I (P>0.10), and fibrosis markers did not significantly differ between HF with diastolic versus those with systolic dysfunction (P>0.10) whereas NT-proBNP mean values were higher in systolic heart failure than in diastolic heart failure (P<0.0001). Conclusions—Fibrosis markers are significantly elevated in elderly individuals with diastolic or systolic HF. These associations remained significant when adjusting for covariates relevant to the aging process.

The Relationship between Serum Markers of Collagen Turnover and Cardiovascular Outcome in the Elderly: The Cardiovascular Health Study

Background— The deposition of collagen fibrils in the myocardial extracellular matrix increases with age and plays a key role in the pathophysiology of heart failure (HF). We sought to determine the predictive value of serum markers of collagen turnover for incident HF and cardiovascular (CV) morbidity, mortality, and all-cause mortality in elderly individuals. Methods and Results— In 880 participants in the Cardiovascular Health Study (mean age, 77±6 years; 48% women), serum levels of carboxyl-terminal peptide of procollagen type I (PIP), carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal peptide of procollagen type III (PIIINP) were measured in 4 groups: HF with reduced ejection fraction (HFREF; n=146, EF <55%); HF with preserved EF (HFPEF; n=175, EF ≥55%), control subjects with CV risk factors but not HF (CVD; n=280), and healthy control subjects free of CV disease (n=279). Relationships between these serum markers and outcome at follow-up of 12±4 years (range, 3–17 years) was determined in six models including those adjusted for conventional risk factors, renal function, NT-proBNP and agents which interfere with collagen synthesis. For the entire cohort, in unadjusted and adjusted models, both PIIINP and CITP were associated with myocardial infarction, incident HF, hospitalization for HF, cardiovascular and all-cause mortality. In healthy control subjects, CITP and PIIINP were associated with all-cause death. In control subjects with risk factors, CITP was associated with incident HF, and in participants with HFPEF, CITP was associated with hospitalization for HF. No collagen biomarker was associated with outcome in participants with HFREF, and PIP was not associated with outcome in the cohort or its subgroups. Conclusions— In both healthy and elderly individuals with CV disease at risk of developing HF, CITP and PIIINP are significantly associated with multiple adverse cardiac outcomes including myocardial infarction, HF, and death. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.

Echocardiographic Evaluation of Left-Ventricular Diastolic Function in Patients with Chronic Pulmonary Hypertension

Different patterns of left-ventricular (LV) diastolic dysfunction were reported in patients with pulmonary hypertension (PHT). There are no data regarding the relationship between the severity of PHT and LV diastolic dysfunction. In order to determine the severity of PHT at which LV diastolic dysfunction occurs and to identify its pattern, we studied by Doppler echocardiography 120 patients with PHT (57 with severe PHT and 63 with mild or moderate PHT) and compared them with 75 normal controls. Systolic pulmonary artery pressure (SPAP) was measured by tricuspid regurgitant jet method and the usual transmitral LV diastolic indices were recorded. LV diastolic dysfunction of impaired relaxation type is most commonly seen in patients with severe PHT. No differences were observed between patients with mild and moderate PHT regarding LV diastolic function. A SPAP ≧60 mm Hg is needed to induce changes in the LV diastolic filling pattern.

Association of annular calcification and aortic valve sclerosis with brain findings on magnetic resonance imaging in community dwelling older adults: the cardiovascular health study.

OBJECTIVES The objective of this study was to investigate the associations of mitral annular calcification, aortic annular calcification, and aortic valve sclerosis with covert magnetic resonance imaging (MRI)-defined brain infarcts. BACKGROUND Clinically silent brain infarcts defined by MRI are associated with increased risk for cognitive decline, dementia, and future overt stroke. Left-sided cardiac valvular and annular calcifications are suspected as risk factors for clinical ischemic stroke. METHODS A total of 2,680 CHS (Cardiovascular Health Study) participants without clinical histories of stroke or transient ischemic attack underwent brain MRI in 1992 and 1993, 1 to 2 years before echocardiographic exams (1994 to 1995). RESULTS The mean age of the participants was 74.5 ± 4.8 years, and 39.3% were men. The presence of any annular or valvular calcification (mitral annular calcification, aortic annular calcification, or aortic valve sclerosis), mitral annular calcification alone, or aortic annular calcification alone was significantly associated with a higher prevalence of covert brain infarcts in unadjusted analyses (p < 0.01 for all). In models adjusted for age, sex, race, body mass index, physical activity, creatinine, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, coronary heart disease, and congestive heart failure, the presence of any annular or valve calcification remained associated with covert brain infarcts (risk ratio: 1.24; 95% confidence interval: 1.05 to 1.47). The degree of annular or valvular calcification severity showed a direct relation with the presence of covert MRI findings. CONCLUSIONS Left-sided cardiac annular and valvular calcifications are associated with covert MRI-defined brain infarcts. Further study is warranted to identify mechanisms and determine whether intervening in the progression of annular and valvular calcification could reduce the incidence of covert brain infarcts as well as the associated risk for cognitive impairment and future stroke.

Elevated cardiac troponin levels do not predict adverse outcomes in hospitalized patients without clinical manifestations of acute coronary syndromes.

The prognostic significance of elevated cardiac troponin levels (CTL) in hospitalized patients with no other evidence of myocardial ischemia or injury is largely unknown. Fifty patients (mean age 61 ± 15 years, 15 women) out of 580 consecutive hospitalized patients were selected based on normal CK-MB and at least 3-fold increase of CTL. The medical charts of these patients were reviewed and a 1-year follow-up was performed. The most frequent admission diagnoses were exacerbation of congestive heart failure (22%), stroke (20%) followed by respiratory failure (6%), cirrhosis (6%), gastrointestinal bleeding (6%), end-stage renal disease (4%), atrial fibrillation (4%) and metastatic malignancies (4%). Abnormal CTL prompted a cardiology consult in 48% of patients, an echocardiogram in 44%, myocardial perfusion study in 10% and coronary angiography in 1 patient. Of 21 deaths, only 1 was related to an acute coronary event. The measurement of CTL in patients without definite clinical or electrocardiographic evidence of myocardial ischemia and with a wide spectrum of clinical diagnoses does not predict in-hospital and at 1 year cardiovascular complications and/or cardiac death.