Dyssynchrony indices to predict response to cardiac resynchronization therapy: a comprehensive prospective single-center study.

BACKGROUND: Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. METHODS AND RESULTS: Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy (P=0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR (P<0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. CONCLUSIONS: These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.

Aortic root replacement with a novel decellularized cryopreserved aortic homograft: postoperative immunoreactivity and early results.

OBJECTIVE: Novel antigen-reduction SynerGraft technology (CryoLife Inc, Kennesaw, Ga) reduces the cellular components of a cadaver homograft with an enzymatic and washing process, leaving the extracellular matrix intact. We report the immunoreactivity (positive panel reactive antibody assay) and early operative results of the CryoLife SynerGraft aortic valve conduit homograft. METHODS: Twenty-two patients (age 53 +/- 14 years, range 31-80 years) from April 2002 to July 2003 underwent aortic root replacement with a CryoLife SynerGraft aortic valve conduit homograft (CryoLife Inc, Kennesaw, Ga) for congenital or acquired aortic valve disease, aortic aneurysm with aortic valve disease, or native or prosthetic aortic valve endocarditis. Baseline percentage positive panel reactive antibody results were negative (<10%) for all and were assessed at 1 month, 3 months, and 1-year. Homograft function was evaluated by echocardiography. RESULTS: Early mortality was 0%. Two late deaths at 1 postoperative year were unrelated to homograft function. At 1 postoperative month, panel reactive antibody results were negative in 20 patients (91%). At 3 months, 19 of 22 patients (86%) had negative results, including 1 with previous positive results. At 1 year, 19 of 20 patients (95%) had negative results, including 2 of the 3 with previous positive results. The mean aortic valve gradients were 12 +/- 8 mm Hg (n = 21) at discharge and 11 +/- 7 mm Hg (n = 18) at 1 year. At a mean follow-up of 30.3 +/- 5.2 months, the mean gradient was 8.8 +/- 6.3 mm Hg. CONCLUSION: The SynerGraft decellularization technology successfully removed antigens from an aortic valve homograft conduit. Aortic root reconstruction with the CryoLife SynerGraft aortic valve homograft resulted in low transvalvular gradients, similar to those seen with standard cryopreserved homografts. These early results suggest an advancement in homograft technology. The low panel reactive antibody response may enhance durability by eliminating immune complex-mediated reaction against the homograft. The lack of allosensitization in patients who may require organ transplantation in the future is an added benefit.

Carvedilol therapy is associated with a sustained decline in brain natriuretic peptide levels in patients with congestive heart failure.

BACKGROUND: Beta-blocker therapy improves symptoms, left ventricular ejection fraction (LVEF), and survival in patients with congestive heart failure, but chronic effects on neurohormones have not been extensively investigated. Therefore, we examined the neurohumoral effects of carvedilol. METHODS: Fifty-five patients with New York Heart Association (NYHA) classes II-III congestive heart failure and LVEF < or =35% entered the study with intention to assess LVEF, NYHA class, plasma brain natriuretic peptide (BNP), N-terminal atrial natriuretic peptide (NANP), big-endothelin, endothelin-1, norepinephrine, and angiotensin II at baseline and at 6 and 12 months after initiation of carvedilol. RESULTS: Forty-six patients completed 12 months of follow-up. Left ventricular ejection fraction improved from 26% +/- 8% at baseline to 39% +/- 14% at 12 months. New York Heart Association class improved from 2.3 +/- 0.4 at baseline to 1.8 +/- 0.7 at 12 months. Brain natriuretic peptide fell from 453 +/- 784 to 208 +/- 393 pg/mL at 6 months and 223 +/- 334 pg/mL at 12 months ( P = .01 vs baseline). N-terminal atrial natriuretic peptide did not change between baseline and 6 months but fell at 12 months (2117 +/- 1678, 2015 +/- 1532, and 1438 +/- 1442 pg/mL, respectively, P = .001 between baseline and 12 months). Angiotensin II was lower at 6 and 12 months than at baseline (12.6 +/- 10, 7.8 +/- 5.5 pg/mL, P < 0.001, and 11.3 +/- 17.1 pg/mL, P = .02, respectively). Left ventricular ejection fraction at 12 months correlated inversely with BNP level at 12 months (r = -0.55, P = .001). CONCLUSIONS: Carvedilol therapy is associated with a sustained decline in BNP and NANP levels. Serial BNP levels can provide some guidance regarding probability of LVEF improvement, but the relationship is not strong enough for BNP levels to supplant measurement of LVEF.

Relationship of myocardial perfusion imaging findings to outcome of patients with heart failure and suspected ischemic heart disease.

BACKGROUND: We retrospectively identified heart failure patients with suspected ischemic heart disease who underwent myocardial perfusion imaging (MPI) to examine the relationship of MPI findings to subsequent patient outcomes. METHODS: The study group consisted of 336 patients with heart failure, left ventricular ejection fraction <45%, and suspected ischemic heart disease who underwent MPI during the period of January 1991 to December 31, 1997. Patients were divided in 3 subgroups: group A (n = 137), large fixed perfusion defects; group B (n = 77), large reversible perfusion defects; and group C (n=122), absence of a large reversible or fixed perfusion defect. RESULTS: Overall, the 5-year mortality rate was high at 49.2% +/- 3.1%. Mortality was significantly different (P =.009) among the 3 subgroups. Groups A and B had a similar 5-year mortality rates >50%. Group C had a relatively better, but still substantial 5-year mortality rate of 40%. The overall revascularization rate was low (9.7% in 5 years). CONCLUSION: These results indicate a high 5-year mortality rate in patients with large myocardial perfusion defects (fixed or reversible) and presumably an ischemic etiology for their heart failure. Patients with no large or absent perfusion defects had more favorable survival outcomes.

Detection of fluconazole-resistant isolates of Candida glabrata by using an agar screen assay.

The ability of a fluconazole-containing agar screen assay to accurately detect isolates of Candida glabrata resistant to the azole antifungal agent fluconazole was evaluated on a collection of 100 clinical isolates of this organism. Results were correlated with the MIC of fluconazole for these isolates and compared with the results of a previously published disk diffusion-based fluconazole resistance screening test. Agar screen assay results were in categorical agreement with MIC-based determinations for 97% (97/100) of the isolates tested. This correlation was higher than that obtained with the disk diffusion technique, which categorized only 87% (87/100) of isolates correctly, and suggests that the agar screening approach can effectively expedite fluconazole susceptibility testing of C. glabrata isolates.

The potential of brain natriuretic peptide as a biomarker for New York Heart Association class during the outpatient treatment of heart failure.

BACKGROUND: Plasma C-terminal atrial natriuretic peptide (C-ANP), N-terminal ANP (N-ANP), and brain natriuretic peptide (BNP) have diagnostic utility in detecting left ventricular dysfunction. Their relative value in monitoring symptom status during the chronic treatment of congestive heart failure (CHF) remains undefined. METHODS AND RESULTS: Ninety-eight subjects with CHF were evaluated. Baseline natriuretic peptides were measured by radioimmunoassay, left ventricular ejection fraction (LVEF) was estimated with echocardiography, and New York Heart Association (NYHA) class was determined independently by attending heart failure specialists. Forty-one subjects were restudied during a 6- to 12-month follow-up period after optimizing therapy. At baseline, all natriuretic peptides and LVEF correlated positively with NYHA class (P <.005). Plasma BNP, however, correlated best with NYHA class. At follow-up, only changes of BNP correlated to changes of NYHA class (P =.04). BNP decreased (-45% +/- 12%, N = 14, P =.002) in subjects whose NYHA class improved whereas BNP remained unchanged (-1% +/- 10%, N = 25, P =.95) in those whose NYHA class was stable. CONCLUSIONS: This investigation demonstrates the superiority of plasma BNP as compared to ANP and LVEF in objectively assessing NYHA class during the chronic treatment of CHF. Given that clinical assessment of CHF is subjective, plasma BNP is a useful objective biomarker in monitoring human CHF in the outpatient setting.

Early detection of central nervous system tuberculosis with the gen-probe nucleic Acid amplification assay: utility in an inner city hospital.

Central nervous system tuberculosis is a serious clinical problem, the treatment of which is sometimes hampered by delayed diagnosis. We investigated the utility of the Gen-Probe nucleic acid amplification assay for the rapid diagnosis of tuberculous meningitis and as a noninvasive method of identifying intracranial tuberculoma.

Long-term outcome and the use of revascularization in patients with heart failure, suspected ischemic heart disease, and large reversible myocardial perfusion defects.

BACKGROUND: The potential role of coronary revascularization in the management of patients with congestive heart failure and suspected ischemic heart disease remains to be defined. Myocardial perfusion imaging can identify patients with ischemic heart disease as the etiology for left ventricular dysfunction who might benefit from revascularization. METHODS: We retrospectively identified heart failure patients with suspected ischemic heart disease who had large reversible perfusion defects to determine their long-term outcome and rate of revascularization. The study group consisted of 77 patients with congestive heart failure, left ventricular ejection fraction <45%, and suspected ischemic heart disease who underwent myocardial perfusion imaging during the period of January 1, 1991, to December 31, 1997, and had large reversible perfusion defects. RESULTS: The 5-year mortality rate was 57.6%. The revascularization rate was only 13% for 5 years of follow-up. The number of patients undergoing revascularization was too small to assess its impact on outcome. CONCLUSION: These results indicate a high 5-year mortality rate and a low utilization of coronary revascularization in patients with heart failure and large reversible perfusion defects. The low rate of revascularization reflects at least in part the absence of the generalizability of the existing literature to the optimal means of treating patients with heart failure and myocardial ischemia and points to the need for a randomized clinical trial.