Nishimura, Rick A.

Background— The pathophysiology of low flow, low gradient severe aortic stenosis (LGSAS) with preserved ejection fraction is poorly understood. It has been proposed that abnormalities of arterial circulation are a major contributor to this syndrome. Methods and Results— We invasively examined systemic arterial afterload (effective arterial elastance, Ea; total arterial compliance, Ca; and systemic vascular resistance index) in patients with LGSAS (mean gradient, <40 mm Hg; aortic valve area, <1.0 cm 2 ) and preserved ejection fraction (≥50%), and compared these findings with patients with high gradient (≥40 mm Hg) severe aortic stenosis (HGSAS) and moderate AS (mean gradient, <40 mm Hg; aortic valve area, >1.0 cm 2 ). Patients with LGSAS (n=36), HGSAS (n=31), and moderate AS (n=19) were similar with respect to age, sex, body size, symptoms, comorbidities, and ejection fraction. Aortic valve area was similar between groups with LGSAS and HGSAS, but the patients with LGSAS had reduced stroke volume index and cardiac index ( P =0.003 for both). In comparison with patients with HGSAS and moderate AS, measures of afterload, including Ea (4.02±0.98 versus 3.13±0.81 and 3.06±0.79 mm Hg·m 2 /mL; P <0.0001) and systemic vascular resistance index (3116±799 versus 2515±645 and 2380±546 dyn·s·m 2 /cm 5 ; P =0.001), were significantly higher in LGSAS, whereas Ca was lower (0.46±0.16 versus 0.57±0.13 and 0.59±0.19 mL/m 2 per mm Hg; P =0.002). All invasive measures of arterial afterload were related to stroke volume index. Conclusions— Patients with LGSAS and preserved ejection fraction display elevated arterial afterload compared with patients with HGSAS and moderate AS. These findings identify systemic arterial effects that contribute to the hemodynamic presentation in patients with LGSAS and help to further define this entity.

Background— The clinical efficacy of alcohol septal ablation for obstructive hypertrophic cardiomyopathy (HCM) has been demonstrated, but the long-term effects of the procedure remain uncertain. This study examined the survival of patients after septal ablation performed in a tertiary HCM referral center. Methods and Results— We examined 177 patients (mean age, 64 years; 68% women) who underwent septal ablation at our institution. Over a follow-up of 5.7 years, survival free of all mortality was no different than the expected survival for a comparable general population, and similar to that of age- and sex-matched patients who underwent isolated surgical myectomy (8-year survival estimate, 79% versus 79%; P =0.64). For the end point of documented sudden cardiac death or unknown cause of death, the incidence per 100 person-year follow-up was 1.31 (95% confidence interval, 0.60–2.38). Residual left ventricular outflow tract gradient after ablation was an independent predictor of long-term survival free of any death. Conclusions— In this nonrandomized study of carefully selected patients undergoing septal ablation by experienced operators in a tertiary referral HCM center, long-term survival was favorable and similar to that of an age- and sex-matched general population, and to patients undergoing surgical myectomy, as well, without an increased risk of sudden cardiac death.

Atrial and brain natriuretic peptides (ANP and BNP) are produced by the heart, and their plasma concentrations are increased in human chronic congestive heart failure. Although separate studies have suggested that circulating levels of the biologically active C-terminal ANP, the biologically inactive N-terminal ANP, and BNP may have diagnostic utility in the detection of left ventricular systolic dysfunction or left ventricular hypertrophy, no studies have directly assessed the relative value of these peptides prospectively. We therefore designed this study to compare the relative ability of the different natriuretic peptides to detect abnormal left ventricular systolic and diastolic function and left ventricular hypertrophy. Using a prospective study design, we investigated 94 patients referred for cardiac catheterization and 15 age-matched normal subjects. The diagnostic abilities of elevated plasma C-terminal ANP, N-terminal ANP-(1-30), and BNP concentrations to identify systolic dysfunction (ejection fraction <45%), diastolic dysfunction (time constant of left ventricular relaxation >55 milliseconds, left ventricular end-diastolic pressure >18 mm Hg), and left ventricular hypertrophy (left ventricular mass index >120 g/m 2 ) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean+3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m 2 . The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-terminal ANP or N-terminal ANP-(1-30) has potential utility for the detection of altered left ventricular structure and function in a patient population at risk for cardiovascular disease.

BackgroundQuantitative Doppler echocardiography and proximal flow convergence methods are validated techniques for quantifying mitral regurgitation. However, the clinical interpretation of the values calculated is hindered by the absence of calibration of ranges of severity in large numbers of patients.Methods and ResultsIn 180 consecutive patients (men, 62%; mean age±SD, 66±11 years), the results of Doppler quantification of isolated mitral regurgitation were calibrated by use of left ventricular angiographic grading performed within 3 months in routine practice and without intervening events. The thresholds of the quantitative variables corresponding to the angiographic grades were identified by maximizing the sum of sensitivity and specificity and minimizing their difference. The mitral regurgitation grade by angiography was 2.7±1.3. The mean value and correlation with angiographic grades for effective regurgitant orifice were 43±37 mm andr=.79 (P<.0001); for regurgitant volume, 62±45 mL andr=.80 (P<.0001); and for regurgitant fraction, 45±17% andr=.78 (P<.0001). Despite some overlap, differences between mitral regurgitation grades were all significant (allP<.05). The thresholds for severe mitral regurgitation (grade 4) were 60 mL, 50%, and 40 mm2for regurgitant volume, regurgitant fraction, and orifice, respectively.ConclusionsIn routine practice in large numbers of patients in a clinical laboratory, Doppler echocardiographic quantification of mitral regurgitation shows highly significant correlation with qualitative angiographic grades. Despite an expected overlap between classes, the calibration by angiography of grading ranges for the quantitative variables provides a framework for their interpretation and allows the definition in clinical practice of thresholds for severe mitral regurgitation.

BackgroundA subgroup of patients with hypertrophic obstructive cardiomyopathy remain severely symptomatic despite optimal medical therapy. Septal myectomy reduces or eliminates left ventricular outflow obstruction and produces marked symptomatic improvement. With the recent advent of alternative methods for treatment of this disorder, such as dual-chamber pacing, it is necessary to establish the risks and benefits of septal myectomy in the modern surgical era.Methods and ResultsThe clinical, ECG, echocardiographic, cardiac catheterization, and surgical data were analyzed for 65 patients 20 to 70 years old with hypertrophic obstructive cardiomyopathy who had surgical treatment between 1986 and 1992. Specific symptoms and overall functional status were evaluated before surgery and at the end of the first postoperative year. Subsequent long-term clinical postoperative follow-up was also obtained. The extent of postoperative improvement was measured by the presence and severity of persistent symptoms, overall New York Heart Association (NYHA) functional class, and patients' self-perceptions of overall improvement. Of the patients, 95% were in NYHA functional class III or IV before surgery: 95% had dyspnea, 62% had angina, 63% had near-syncope, and 23% had syncope. The overall early mortality rate was 4.6%; there was no mortality among the 45 patients who underwent isolated septal myectomy. At the 1-year postoperative evaluation, 89% of survivors were in NYHA functional class I or II, and 47% believed that they had 100% improvement. Significant improvement (as defined) was seen in 67% of patients with dyspnea, 90% with angina, 86% with near-syncope, and 100% with syncope. The 5-year survival rate was 92%.ConclusionsThe results of the present study reaffirm the efficacy of surgical treatment of hypertrophic obstructive cardiomyopathy in patients who are severely symptomatic despite optimal medical therapy and serve as a useful reference by which the surgical approach can be compared with new and potentially promising treatment alternatives.

BACKGROUND Dilated cardiomyopathy is an important cause of morbidity and mortality among patients with congestive heart failure. Hemodynamic and prognostic characterization are critical in guiding selection of medical and surgical therapies. METHODS AND RESULTS A cohort of 102 patients with the clinical diagnosis of dilated cardiomyopathy who underwent echocardiographic examination between 1986 and 1990 was identified and followed up through July 1, 1991. Patients with moderate or severe symptoms had lower indices of systolic function and greater left atrial and right ventricular dilation. Mitral inflow Doppler signals were characterized by a restrictive left ventricular filling pattern. In multivariate logistic regression analysis, deceleration time, ejection fraction, and peak E velocity were independently associated with symptom status. Over a mean follow-up of 36 months, 35 patients died. Kaplan-Meier estimated survival at 1, 2, and 4 years was 84%, 73%, and 61%, respectively, and was significantly poorer than that of an age- and sex-matched population. The subgroup with an ejection fraction < 0.25 and deceleration time < 130 milliseconds had a 2-year survival of only 35%. The subgroup with ejection fraction < 0.25 and deceleration time > 130 milliseconds had an intermediate 2-year survival of 72%, whereas patients with an ejection fraction > or = 0.25 had 2-year survivals > or = 95% regardless of deceleration time. In multivariate analysis, ejection fraction and systolic blood pressure were independently predictive of subsequent mortality. Mitral deceleration time was significant in univariate analysis. CONCLUSIONS In patients with the clinical diagnosis of dilated cardiomyopathy, markers of diastolic dysfunction correlated strongly with congestive symptoms, whereas variables of systolic function were the strongest predictors of survival. Consideration of both ejection fraction and deceleration time allowed identification of subgroups with divergent long-term prognoses.

BACKGROUND The instantaneous pressure gradient between the left ventricle and left atrium during systole can be calculated from the mitral regurgitation Doppler velocity curve. The purpose of our study was to determine the accuracy of measuring the time constant of relaxation (TAU) derived from the Doppler mitral regurgitation signal by comparing it with simultaneous high-fidelity left ventricular pressure measurements in humans. METHODS AND RESULTS Twenty-five patients had continuous-wave Doppler mitral regurgitation recordings performed with simultaneous high-fidelity left ventricular pressure measurements. Fifteen of these patients had measurements of six to eight beats at various RR intervals. Doppler velocity curves were converted to left ventricular pressure curves by different methods through application of the modified Bernoulli equation at 3-msec intervals. The correlation between catheter-derived and Doppler-derived TAU was best when a zero asymptote and knowledge of the left ventricular end-diastolic pressure were used. A less optimal but acceptable method used the addition of 20 mm Hg to the Doppler-derived ventriculoatrial gradient. Use of a nonzero asymptote for calculation of TAU yielded poor correlation between catheter and Doppler measurements. The correlation of percentage change in Doppler-derived TAU plotted against percentage change in catheter-derived TAU was poor. CONCLUSIONS The descending limb of the Doppler-derived mitral regurgitation velocity signal can be used as a semiquantitative estimate of the rate of ventricular relaxation. This method requires knowledge of left atrial pressure and may not be sufficiently accurate for detecting small changes in the rate of relaxation on a beat-to-beat basis.

Background —Dual-chamber pacing (DDD) has been proposed as a treatment alternative to surgery for severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), based largely on uncontrolled studies. Methods and Results —This prospective, multicenter trial assessed pacing in 48 symptomatic HCM patients with ≥50 mm Hg basal gradient, refractory to drug therapy. Patients were randomized to 3 months each of DDD pacing and pacing backup (AAI-30) in a double-blind, crossover study design, followed by an uncontrolled and unblinded 6-month pacing trial. With randomization, no significant differences were evident between pacing and no pacing for subjective or objective measures of symptoms or exercise capacity, including NYHA functional class, quality of life score, treadmill exercise time or peak oxygen consumption. After 6 additional months of unblinded pacing, functional class and quality of life score were improved compared with baseline ( P <0.01), but peak oxygen consumption was unchanged. Outflow gradient decreased 40%, 82±32 mm Hg to 48±32 mm Hg ( P <0.001), and was reduced in 57% of patients but showed no change or an increase in 43%. At 12 months, 6 individual patients (12%) showed improved functional capacity; each was 65 to 75 years of age. Left ventricular wall thicknesses in the overall study group showed no remodeling between baseline (22±5 mm) and 12 months (21±5 mm; P= NS). Conclusions —(1) Pacing cannot be regarded as a primary treatment for obstructive HCM; (2) with randomization, perceived symptomatic improvement was most consistent with a substantial placebo effect; (3) longer, uncontrolled pacing periods were associated with some subjective benefit but unaccompanied by objective improvement in cardiovascular performance and should be interpreted cautiously; (4) modest reduction in outflow gradient was achieved in most patients; and (5) a small subset (12%) ≥ 65 years of age showed a clinical response, suggesting that DDD pacing could be a therapeutic option for some elderly patients.