Evaluation of the left ventricular anatomy in hypertrophic cardiomyopathy: comparison between echocardiography and cardiac magnetic resonance imaging.

AIM: The aim of this study was to assess the relationship between echocardiographic indexes of left ventricular (LV) hypertrophy with LV mass (LVM) obtained at cardiac magnetic resonance (CMR) in a population of patients with hypertrophic cardiomiopathy (HCM). METHODS: Thirty-nine patients with HCM underwent echocardiography and CMR. By echocardiography maximal wall thickness (MWT), Spirito' and Maron's hypertrophy index and the Wigle's score were obtained. Absolute LVM was measured through CMR and indexed to body surface area (LVMi). Data were analysed using linear regression analysis. RESULTS: In 31% of patients there was an incomplete echocardiographic LV anatomic characterization. However, there was a good correlation between MWT measured at echocardiography and at CMR (P<0.001; r=0.755). Overall echocardiographic indexes of LV hypertrophy correlate with either LVM and LVMi: MWT (P=0.008, r=0.420 and P=0.003, r=0.467, respectively); Spirito' and Maron's hypertrophy index (P=0.003, r=0.551 and P=0.001, r=0.606, respectively) and Wigle's score (P=0.004, r=0.522 and P=0.004, r=0.522, respectively). CONCLUSION: In our HCM population, although a complete anatomic LV anatomic characterization was not obtained by echocardiography in all patients, echocardiographic hypertrophic indexes showed a good correlation with LVM obtained by CMR.

Pathogenesis of hypertrophic cardiomyopathy. Impact of growth factors on left ventricular anatomy.

AIM: The aim of this study was to evaluate the effect of insulin-like growth factor 1 (IGF1) and transforming growth factor beta-1 (TGFbeta-1) on collagen turnover, left ventricular (LV) hypertrophy and on passive diastolic function of the LV in hypertrophic cardiomyopathy (HCM). METHODS: This study group comprised 34 patients with non-dilated HCM. Procollagen I amino-terminal propeptide (PINP) and collagen I carboxy-terminal telopeptide (ICTP) were measured by radioimmunoassay. Matrix metalloproteinase 9 (MMP 9), IGF1 and TGFalfa-1 were determined by enzyme-linked immunosorbent assay. The difference in duration between transmitral forward (A) and pulmonary venous retrograde (Ar) waves, was considered as an estimate of passive diastolic function; the ratio between the peak flow velocity at rapid filling at the mitral level (E) and E' measured by tissue Doppler was considered an estimate of active diastolic function. LV mass was measured and normalized to body surface area (LVMi) by cardiac magnetic resonance imaging. RESULTS: LVMi correlates to E/E' (r=0.597, P=0.019 ) and is inversely related to A-Ar (r=0.453, P=0.015). TGFbeta-1 is directly related to active MMP 9 (r=0.439, P=0.012 ). IGF1 is directly related to PICP-ICTP (r=0.347, P=0.501), that expresses the balance between collagen I synthesis and its degradation. CONCLUSION: The study demonstrated that in HCM, LVMi influences active and passive diastolic dysfunction and that IGF1 stimulates collagen synthesis and TGFbeta-1 is related to LV hypertrophy.

Infective endocarditis in hypertrophic cardiomyopathy: prevalence, incidence, and indications for antibiotic prophylaxis.

BACKGROUND: The literature on infective endocarditis in hypertrophic cardiomyopathy (HCM) is virtually confined to case reports. Consequently, the risk of endocarditis in HCM remains undefined. METHODS AND RESULTS: We assessed the occurrence of endocarditis in 810 HCM patients evaluated between 1970 and 1997. Endocarditis was diagnosed in 10 patients, 2 of whom were excluded from analysis of prevalence and incidence because they were referred for acute endocarditis. At first evaluation, echocardiographic features consistent with prior endocarditis were identified in 3 of 808 patients, a prevalence of 3.7 per 1000 patients (95% CI, 0.8 to 11). Of 681 patients who were followed, 5 developed endocarditis, an incidence of 1.4 per 1000 person-years (95% CI, 0.5 to 3.2); outflow obstruction was present in each of these 5 patients and was associated with the risk of endocarditis (P=0.006). In the 224 obstructive patients, incidence of endocarditis was 3.8 per 1000 person-years (95% CI, 1.6 to 8.9) and probability of endocarditis 4. 3% at 10 years. Left atrial size was also associated with the risk of endocarditis (P=0.007). In patients with both obstruction and atrial dilatation (>/=50 mm), incidence of endocarditis increased to 9.2 per 1000 person-years (95% CI, 2.5 to 23.5). Analysis of all 10 patients with endocarditis identified outflow obstruction in each and atrial dilatation in 7. CONCLUSIONS: Endocarditis in HCM is virtually confined to patients with outflow obstruction and is more common in those with both obstruction and atrial dilatation. These results indicate that antibiotic prophylaxis is required only in patients with obstructive HCM.

Isovolumic relaxation period in hypertrophic cardiomyopathy: assessment by radionuclide angiography.

Left ventricular isovolumic relaxation and the relation between relaxation and filling were studied in 90 patients with hypertrophic cardiomyopathy and 29 control subjects using radionuclide angiography. The isovolumic relaxation period was determined automatically on left ventricular time-activity curves as the interval between minimal volume and onset of rapid filling. In 17 patients, M-mode echocardiography performed simultaneously with radionuclide angiography demonstrated that onset of mitral valve opening correlated well with onset of rapid filling (r = 0.84, p less than 0.001). The isovolumic relaxation period was longer in patients with hypertrophic cardiomyopathy than in control subjects (95 +/- 44 versus 50 +/- 23 ms, p less than 0.01) and was longer in patients without an outflow tract gradient at rest than in patients with a gradient (109 +/- 37 versus 86 +/- 35 ms, p less than 0.05). In these patients without obstruction, a weak linear relation between duration of the isovolumic period and peak filling rate was found (r = 0.48, p less than 0.02). Filling was impaired in patients with hypertrophic cardiomyopathy, as assessed by lower peak filling rate (3.2 +/- 1.2 versus 3.5 +/- 0.5 end-diastolic volume/s, p less than 0.05) and prolonged time to peak filling rate (185 +/- 44 versus 145 +/- 20 ms, p less than 0.01) compared with values in control subjects. The delay in time to peak filling rate was caused primarily by the prolonged isovolumic period, because the interval from onset of rapid filling to peak filling rate was similar in patients with hypertrophic cardiomyopathy and control subjects (87 +/- 31 versus 95 +/- 25 ms, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of induced asynchrony on left ventricular diastolic function in patients with coronary artery disease.

OBJECTIVES: This study was designed to increase asynchrony with sequential atrioventricular (AV) pacing and to study its effects on left ventricular isovolumetric relaxation, rapid filling and stiffness. BACKGROUND: Left ventricular nonuniformity is a major determinant of diastolic function. METHODS: Thirteen patients with coronary artery disease were studied by simultaneous equilibrium radionuclide angiography and cardiac catheterization during atrial and AV pacing. Ejection fraction and peak filling rate were measured by radionuclide angiography. Regional analysis was obtained by analyzing time-activity curves of four left ventricular sectors; systolic and diastolic asynchrony were evaluated as the coefficient of variation of time to end-systole and, respectively, time to peak filling rate in the four sectors. Cardiac index and left ventricular pressure were measured with high fidelity catheters at cardiac catheterization. The time constant of isovolumetric relaxation was derived from left ventricular pressure. Pressure-volume loops were assembled and constants of chamber stiffness were computed. RESULTS: Atrioventricular pacing led to a decrease in cardiac index (3.7 +/- 0.9 to 3.3 +/- 0.8 liters/min per m2, p = 0.01) and peak filling rate (352 +/- 125 to 287 +/- 141 ml/s, p = 0.03; 2.4 +/- 0.8 to 2.0 +/- 0.8 end-diastolic counts/s, p = 0.02; 4 +/- 1.3 to 3.2 +/- 1.0 stroke counts/s, p = 0.008). The time constant of isovolumetric relaxation increased (57 +/- 10 to 64 +/- 12 ms, p = 0.04) and the global diastolic pressure-volume relation shifted upward. CONCLUSIONS: Atrioventricular pacing induces left ventricular asynchrony, which is associated with a slower rate of isovolumetric relaxation. The isovolumetric relaxation lasts after the filling phase has begun, thereby reducing the rate of rapid filling.

Evaluation of left ventricular asynchrony by radionuclide angiography: comparison of phase and sector analysis.

UNLABELLED: The aim of this study was to assess the optimal method to evaluate asynchrony in equilibrium radionuclide angiography (RNA). METHODS: We studied 20 patients (14 males and 6 females, age range 25-60 yr) with RNA during atrial and sequential atrioventricular (AV) pacing, which increased left ventricular (LV) asynchrony. Both studies were performed at the same heart rate. Asynchrony was assessed either on phase images, by computing the standard deviation of the phase distribution (SD-P) and by sector analysis. Systolic and diastolic asynchrony were evaluated as the coefficient of variation of time to end systole (CV-TES) and time to peak filling rate (CV-TPFR) in four sectors. In addition, phase values were computed on time-activity curves from the same sectors, and their standard deviation (SD-Psec) was computed. RESULTS: During atrial pacing SD-P was 32.3 degrees +/- 6.7 degrees and did not change during AV pacing (32.1 degrees +/- 5.6 degrees, p = n.s.). Both CV-TES and CV-TPFR had a significant increase during AV pacing (from 7.7% +/- 3.9% to 11.5% +/- 6.4%, p < 0.01, and from 8.4 degrees +/- 5.8 degrees to 12.9 degrees +/- 6.7 degrees, p < 0.001). AV pacing led to a significant increase in SD-Psec (from 6.3 degrees +/- 4.0 degrees to 12.6 degrees +/- 9.7 degrees, p < 0.05). Moreover, reproducibility was assessed in 15 additional age-matched patients. The results of the reproducibility study indicate a better repeatability for CV-TES and CV-TPFR. CONCLUSIONS: The findings of this study suggest that sector analysis with calculation of indices of LV systolic and diastolic asynchrony is better suited for quantitation of LV temporal nonuniformity.

Diastolic function in acute myocardial infarction: a radionuclide study.

We studied left ventricular diastolic function by equilibrium gated radionuclide angiography in patients as follows: 75 with acute myocardial infarction (AMI), 35 with anterior or anteroseptal necrosis (Group A) and 40 with inferior, inferolateral, or posterior necrosis (Group I). The ejection fraction (EF) was lower in Group A than Group I (41.9 +/- 2.5 vs. 57.1 +/- 2.0%, p less than 0.001), as was peak diastolic filling rate normalized to end diastolic volume (PDFR-EDV/sec) (1.9 +/- 0.1 vs. 2.4 +/- 0.1 EDV/sec, p less than 0.05). PDFR normalized to stroke volume was similar in both groups. An excellent linear correlation was found between EF and PDFR-EDV/sec in the total study population. Isovolumic relaxation period (IRP) was beyond our upper normal value of 94 msec in 64% of patients and it was shorter in Group A than I (95.8 +/- 12.7 vs. 147.0 +/- 13.6 msec, p less than 0.05). The presence of shorter IRP in Group A than in I is probably a result of an earlier mitral valve opening as a consequence of higher left atrial pressure.

Assessment of left ventricular diastolic function: comparison of contrast ventriculography and equilibrium radionuclide angiography.

Twenty-two patients with coronary artery disease were studied first by radionuclide angiography (RNA) and then by contrast ventriculography. Cardiac medications were discontinued at least 72 hr before study. The patients were studied during atrial pacing at heart rates close to their spontaneous sinus rhythm. Contrast ventriculography was performed at 50 frames/sec in the 30 degrees right anterior oblique projection using 40 ml of a nonionic contrast medium (iopamidol) at a flow rate of 10-12 ml/sec. The contours of the left ventricular silhouette at contrast ventriculography were traced, frame by frame, on a graphic table with a digitizing penlight. Equilibrium 99mTc RNA was performed in the best septal 45 degrees left anterior oblique projection, acquiring 150,000 cts/frame, at 50 frames/sec and with a 5% gate tolerance. Time-activity curves from both end-diastolic and end-systolic ROIs were built and interpolated. Both RNA and contrast ventriculography volume curves were filtered with Fourier five harmonics. A close relationship was found between RNA and contrast ventriculography measurements of peak filling rate normalized to end-diastolic cps (r = 0.87, p less than 0.001) and stroke count (r = 0.87, p less than 0.001), ejection fraction (r = 0.94, p less than 0.001). Thus, in patients with coronary artery disease, LV filling can be accurately assessed using RNA.

Identification of viable myocardium in patients with chronic coronary artery disease using rest-redistribution thallium-201 tomography: optimal image analysis.

UNLABELLED: With the widely used 50% threshold, sensitivity is high, but specificity is low in detecting viable myocardium on 201Tl SPECT. In this study, we sought to identify the best threshold for semiquantitative 201Tl analysis. METHODS: Rest-redistribution 201Tl SPECT was performed in 46 patients with chronic coronary artery disease before and after myocardial revascularization. Regional function was evaluated by two-dimensional echocardiography before and after myocardial revascularization using a 3-point scale (1 = normal, 2 = hypokinetic, 3 = a/dyskinetic). Myocardial segments with abnormal systolic function were defined as viable if the systolic function score decreased > or = 1 after myocardial revascularization. A second group of 12 patients with chronic coronary artery disease constituted the validation population. Sensitivity-specificity curves, as well as receiver operating characteristic curves, for rest and redistribution mages were generated by varying the 201Tl uptake threshold. RESULTS: A 65% threshold uptake using resting images was found to be the best for detecting a/dyskinetic segments that improve after myocardial revascularization from those that do not improve. Sensitivity was lower with a 65% threshold (75%) than with a 50% threshold (90%, p < 0.05), but specificity was higher (76% versus 26%, p < 0.05) resulting in better accuracy (76% versus 57%, p < 0.05) and positive predictive value (77% versus 55%), while the negative predictive value was not different (69% versus 75%, p not significant). The area under the receiver operating characteristic curve was significantly (p < 005) larger for rest (0.80 +/- 0.05) as opposed to redistribution (0.72 +/- 0.05) images. Similar results were obtained in a subgroup of patients with low ejection fraction. Significant correlations between the percentage of revascularized viable segments and both the change in ejection fraction and in postrevascularization ejection fraction were found. When these findings were applied in the validation group, a gain in specificity, accuracy and positive predictive value was obtained with the 65% threshold compared with the 50% threshold. CONCLUSION: This study demonstrated that analysis of resting images and use of the 65% 201Tl uptake threshold is preferable for separating viable from not viable dyssynergic myocardial segments in patients with chronic coronary artery disease.

Hemodynamic response to exercise after propranolol in patients with mitral stenosis.

Hemodynamic response to exercise before and 10 minutes after propranolol (5 mg intravenously) was studied in 10 young patients with pure mitral stenosis who had normal sinus rhythm and no cardiac failure. After propranolol the mean heart rate and cardiac index at rest were lower than during the control state (respectively, 95 +/- 4 versus 82 +/- 3 beats/min, P less than 0.005; 3.4 +/- 0.2 versus 2.8 +/- 0.1 liters/min per m2, P less than 0.025). As a result, the mean pulmonary wedge pressure and mean mitral valve gradient at rest were lower (respectively, 22 +/- 2 versus 18 +/- 2 mm Hg, P less than 0.005; 24 +/- 2 versus 17 +/- 2 mm Hg, P less than 0.001). During exercise after propranolol the values of pulmonary wedge pressure and mitral valve gradient were lower than control values during exercise (respectively, 39 +/- 3 versus 30 +/- 2 mm Hg, P less than 0.005; 44 +/- 3 versus 32 +/- 3 mm Hg, P less than 0.005), again because of the lower heart rate and cardiac index (130 +/- 6 versus 104 +/- 6 beats/min, P less than 0.001; 4.6 +/- 3 versus 3.7 +/- 2 liters/min per m2, P less than 0.01). Left ventricular end-diastolic pressure and stroke index showed no significant changes. Thus, propranolol may benefit patients with pure mitral stenosis with sinus rhythm and no cardiac failure whose symptoms occur during those reversible conditions characterized by an increase in heart rate or cardiac output, or both.

Normalization of left ventricular nonuniformity late after valve replacement for aortic stenosis.

The aim of the present study was to evaluate nonuniformity in pressure overload hypertrophy due to aortic stenosis. Twenty patients were included in the present analysis. Ten patients with severe aortic stenosis were studied preoperatively as well as early (21 +/- 8 months) and (89 +/- 21 months) after aortic valve replacement (AVR) using left ventricular biplane angiograms, high-fidelity pressure measurements and endomyocardial biopsies. Ten normal subjects served as controls. LV systolic function was assessed from biplane ejection fraction, and diastolic function from the time constant of relaxation, the peak filling rate and the constant of myocardial stiffness. Nonuniformity was evaluated from the coefficient of variation of the time to end-systole (systolic asynchrony) and peak filling rate (diastolic asynchrony) of 12 regions in right anterior oblique and left anterior oblique projection. Ejection fraction was comparable in patients with aortic stenosis and in controls, whereas preoperatively diastolic dysfunction with prolonged relaxation and increased stiffness was present in patients with aortic stenosis and was normalized late after AVR. LV systolic asynchrony was present (>25D of controls) in 7 and diastolic asynchrony in 10 of 10 patients with aortic stenosis. Early as well as late after AVR systolic asynchrony was normalized in 9 of 10 patients. Diastolic asynchrony was present early AVR in all but one patient, although there was a significant improvement with respect to the preoperative evaluation. Late after AVR there was a normalization of diastolic asynchrony in 9 of 10 patients with aortic stenosis. Thus, it is concluded that systolic asynchrony is normalized early after AVR probably due to its load-sensitivity, whereas diastolic asynchrony persists probably due to residual LV hypertrophy with increased interstitial fibrosis and myocardial stiffness. Late after AVR, diastolic asynchrony is normalized due to structural remodeling with regression of both myocardial hypertrophy and interstitial fibrosis.

Influence of left ventricular asynchrony on filling in coronary artery disease.

To evaluate whether the extent of left ventricular (LV) asynchrony plays a role in the impairment of LV rapid filling in patients with coronary artery disease (CAD), 48 patients underwent both radionuclide angiography and cardiac catheterization. Patients were divided into group I (n = 33), with normal LV kinesis or only mild hypokinesia, and group II (n = 15), with LV dyskinesia or akinesia. Radionuclide ejection fraction was higher in group I than in group II (62 +/- 12 vs 44 +/- 20%; p less than 0.001). Peak filling rate was significantly lower in group II (1.9 +/- 0.8 vs 2.6 +/- 0.9 end-diastolic counts/s; p less than 0.01). Time to end-systole coefficient of variation, an index of the extent of LV asynchrony, was significantly higher in group II than in group I (43 +/- 10 vs 35 +/- 6; p less than 0.0002). In group I, a highly significant inverse relation was found between this index of asynchrony and peak filling rate (r = 0.71; p less than 0.0001). This correlation was found even when time to end-systole coefficient of variation was normalized to the RR interval (r = 0.49; p less than 0.01) and when peak filling rate was expressed in stroke counts (r = 0.57; p less than 0.001). The correlation between peak filling rate and index of asynchrony was maintained up to an end-systole coefficient of variation value of approximately 35. In group II patients (most with an asynchrony value greater than or equal to 35) no relation was found between time to end-systole coefficient of variation and peak filling rate.

Exercise capacity in hypertrophic cardiomyopathy depends on left ventricular diastolic function.

Some studies have demonstrated that left ventricular (LV) diastolic function is the principal determinant of impaired exercise capacity in hypertrophic cardiomyopathy (HC). In this study we sought the capability of echocardiographic indexes of diastolic function in predicting exercise capacity in patients with HC. We studied 52 patients with HC while they were not on drugs;12 of them had LV tract obstruction at rest. Diastolic function was assessed by M-mode and Doppler echocardiography by measuring: (1) left atrial fractional shortening, and the slope of posterior aortic wall displacement during early atrial emptying on M-mode left atrial tracing; and (2) Doppler-derived transmitral and pulmonary venous flow velocity indexes. Exercise capacity was assessed by maximum oxygen consumption by cardiopulmonary test during cycloergometer upright exercise. Maximum oxygen consumption correlated with the left atrial fractional shortening (r = 0.63, p <0.001), the slope of posterior aortic wall displacement during early atrial emptying (r = 0.55, p <0.001), age (r = -0.50; p <0.001), pulmonary venous diastolic anterograde velocity (r = 0.41, p <0.01), and the systolic filling fraction (r = -0.43; p <0.01). By stepwise multiple linear regression analysis, left atrial fractional shortening and the pulmonary venous systolic filling fraction were the only determinants of the maximum oxygen consumption (multiple r = 0.70; p <0.001). Exercise capacity did not correlate with Doppler-derived transmitral indexes. Thus, in patients with HC, exercise capacity was determined by passive LV diastolic function, as assessed by the left atrial M-mode and Doppler-derived pulmonary venous flow velocities.

Influence of left ventricular cavity size on clinical presentation in hypertrophic cardiomyopathy.

The aim of this study was to assess whether left ventricular (LV) cavity size relates to functional impairment and syncope in patients with hypertrophic cardiomyopathy (HC). LV diastolic dysfunction influences functional limitation in HC. A reduced LV end-diastolic dimension may underlie impaired diastolic properties and be implicated in hemodynamic syncope. Eighty-two consecutive patients with HC (off drugs, in sinus rhythm) underwent echocardiography to measure LV end-diastolic dimension in the short-axis view (indexed to the body surface area) and radionuclide angiography (n = 50) to calculate peak filling rate (normalized to stroke counts/s). Patients in New York Heart Association functional classes II to IV had smaller LV end-diastolic dimension (23.2 +/- 2.6 vs 25.5 +/- 2.5 mm/M2, p = 0.0001) and lower peak filling rate (4.3 +/- 1.4 vs 5.1 +/- 1.3 stroke counts/s, p = 0.036) than those in New York Heart Association class I. LV end-diastolic diameter was correlated to peak filling rate (r = 0.37; p = 0.008). The most potent predictors of functional limitation were LV end-diastolic dimension (relative risk [RR] 0.63, confidence interval [CI] 0.45 to 0.88; p = 0.008), age (RR 1.09, CI 1.03 to 1.17; p = 0.003), and LV thickness score (RR 1.08, CI 1.02 to 1.13; p = 0.003). LV cavity size was smaller in patients with functional limitation irrespective of obstruction and hypertrophy. Patients with differed from those without a history of syncope for a smaller LV end-diastolic dimension (23.2 +/- 2.5 vs 25.0 +/- 2.7 mm/M2, p = 0.008), which was the only independent predictor of syncope (RR 0.77, CI 0.63 to 0.95; p = 0.013). Thus, a small LV cavity size is associated with functional limitation and history of syncope in HC.

Effects of diltiazem on left ventricular systolic and diastolic function in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HC) is characterized by impaired diastolic function, and left ventricular (LV) outflow tract obstruction in about one-fourth of patients. Verapamil improves diastolic properties, but may have dangerous adverse effects. This study investigates the effects of diltiazem on hemodynamics and LV function in 16 patients with HC who were studied with cardiac catheterization and simultaneous radionuclide angiography. Studies were performed during atrial pacing (15 beats above spontaneous rhythm) at baseline and during intravenous diltiazem administration (0.25 mg x kg(-1) over 2 minutes, and 0.014 mg x kg(-1) x min(-1). Diltiazem induced a systemic vasodilation (cardiac index: 3.4 +/- 1.0 to 4.0 +/- 1.0 L x min(-1) x m(-2), p = 0.003; aortic systolic pressure: 116 +/- 16 to 107 +/- 19 mm Hg, p = 0.007; systemic resistance index: 676 +/- 235 to 532 +/- 193 dynes x s x cm(-5) x m(-2), p = 0.006), not associated with changes in the LV outflow tract gradient. The end-systolic pressure/volume ratio decreased (30 +/- 42 to 21 +/- 29 mm Hg x ml(-1) x m(-2); p = 0.044). Pulmonary artery wedge pressure (11 +/- 5 to 15 +/- 6 mm Hg, p = 0.006), and peak filling rate increased (4.1 +/- 1.3 to 6.0 +/- 2.4 stroke counts x s(-1), p = 0.004). The time constant of isovolumetric relaxation tau decreased (74 +/- 40 to 59 +/- 38 ms, p = 0.045). The constant of LV chamber stiffness did not change. Thus, active diastolic function is improved by the acute administration of diltiazem by both direct action and changes in hemodynamics and loading conditions. LV outflow tract gradient does not increase despite systemic vasodilation. In some patients, however, a marked increase in obstruction and a potentially harmful elevation in pulmonary artery wedge pressure do occur. Passive diastolic function is not affected.

Noninvasive evaluation of left ventricular diastolic function in hypertrophic cardiomyopathy.

Diastolic dysfunction is common in hypertrophic cardiomyopathy (HC). Previous studies suggest that Doppler transmitral flow velocity profiles, and the left atrial (LA) M-mode echogram can be used noninvasively to evaluate left ventricular (LV) diastolic function. However, this has not been proved in HC. In this study we determined the relation of Doppler transmitral flow velocity profiles and the LA M-mode echograms to invasive indexes of LV diastolic function in patients with HC. We studied 25 patients with HC, while off drugs, and calculated LA global and active fractional shortening and the slope of both early and late displacement of the posterior aortic wall during LA emptying by M-mode echocardiography. We calculated peak velocity of early (E) and atrial (A) filling, E to A ratio, and E-wave deceleration time by pulsed Doppler echocardiography, and simultaneous radionuclide angiography, LV pressures, time constant of isovolumic relaxation tau, and the constant of chamber stiffness k by cardiac catheterization. The time constant of isovolumic relaxation tau correlated with the slope of early posterior aortic wall displacement (r = 0.59; p <0.01). LV end-diastolic pressure correlated with global LA fractional shortening (r = -0.75; p <0.001); the constant of chamber stiffness k correlated with active LA fractional shortening (r = -0.53; p <0.02). In a subset of 13 patients, in whom echocardiography and cardiac catheterization were performed simultaneously, similar results were found. LA M-mode recordings provide a more reliable noninvasive assessment of diastolic function in HC than mitral Doppler indexes.

Effects of intravenous verapamil administration on left ventricular diastolic function in systemic hypertension.

The effects of intravenous verapamil administration (0.1 mg/kg as a bolus followed by an infusion of 0.007 mg/kg/min) were studied using high-temporal-resolution radionuclide angiography in 27 patients with hypertension. Verapamil administration increased heart rate from 69 +/- 11 to 75 +/- 12 beats/min (p less than 0.001) and decreased systolic, diastolic and mean blood pressures (BPs) from 155 +/- 21/102 +/- 12 mm Hg (mean 119 +/- 14) to 142 +/- 19/95 +/- 12 mm Hg (mean 109 +/- 13) (p less than 0.001 for all). Ejection fraction decreased significantly (from 65 +/- 10% to 60 +/- 11%, p less than 0.005); peak filling rate, however, increased significantly only in patients in whom it was subnormal in the basal study (from 2.2 +/- 0.4 to 3.0 +/- 0.6 end-diastolic counts/s, p less than 0.001). These latter patients had significantly higher values of left ventricular (LV) mass index than patients with normal or increased peak filling rate (129 +/- 22 vs 112 +/- 22 g/m2, respectively, p less than 0.05). The isovolumic relaxation period changes were inversely related to the baseline values (r = 0.83, p less than 0.001). In the subgroup of patients in whom isovolumic relaxation period lengthened, time to end systole decreased (from 360 +/- 31 to 329 +/- 30 ms, p less than 0.025) and time to onset of rapid filling increased (from 420 +/- 31 to 451 +/- 34 ms, p less than 0.025), whereas these 2 intervals had opposite patterns in patients in whom isovolumic relaxation period decreased or did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of diastolic function after reversal of left ventricular hypertrophy induced by long-term antihypertensive treatment with tertatolol.

In 15 previously untreated hypertensive subjects with left ventricular (LV) hypertrophy who responded favorably (supine blood pressure less than or equal to 140/90 mm Hg) to antihypertensive treatment with a nonselective beta-blocking agent, tertatolol, the effects of reversal of LV hypertrophy on systolic and diastolic function were assessed. Patients underwent echocardiographic and radionuclide studies in control conditions (phase 1), after 1 month of blood pressure normalization (phase 2), after reversal of LV hypertrophy or at least a 20% reduction of LV mass compared to basal value (phase 3) and finally, after a 1-month washout (phase 4). In phase 2, blood pressure (130 +/- 2/85 +/- 1 vs 148 +/- 4/104 +/- 1 mm Hg) and heart rate (59 +/- 1 vs 76 +/- 2 beats/min) decreased (both p less than 0.01); LV mass remained unchanged. There were improvements in peak filling rate (end-diastolic volume/s) (2.4 +/- 0.1 vs 2.0 +/- 0.1), ejection fraction (65 +/- 1 vs 61 +/- 1%) and their ratio (stroke counts/s) (3.7 +/- 0.2 vs 3.2 +/- 0.1) (all p less than 0.05). In phase 3, blood pressure and heart rate were unchanged and reversal of LV hypertrophy was accompanied by a further increase in peak filling rate (2.9 +/- 0.1), ejection fraction (69 +/- 1%) and their ratio (4.1 +/- 0.1) compared to phase 2 (all p less than 0.01). Finally, in phase 4 blood pressure and heart rate returned to the basal value, but peak filling rate (2.7 +/- 0.1) and ejection fraction (65 +/- 1%), although reduced compared to phase 3, were still higher than phase 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intravenous verapamil on left ventricular relaxation and filling in stable angina pectoris.

Left ventricular (LV) diastolic function is often impaired in coronary artery disease (CAD). To assess whether verapamil could improve LV diastolic properties, 12 patients with CAD undergoing right- and left-sided cardiac catheterization, as well as simultaneous radionuclide angiography, were studied before and during intravenous administration of verapamil (0.1 mg/kg as a bolus followed by 0.007 mg/kg/min). The heart rate was kept constant by atrial pacing in both studies. LV pressure-volume relations were obtained. Verapamil decreased LV systolic pressure (130 +/- 22 to 117 +/- 16 mm Hg, p less than 0.01) and the end-systolic pressure/volume ratio (2.4 +/- 1.3 to 1.6 +/- 0.5 mm Hg/ml, p less than 0.05), and increased LV end-diastolic (13 +/- 4 to 16 +/- 4 mm Hg, p less than 0.02) and pulmonary capillary pressures (10 +/- 5 to 12 +/- 5 mm Hg, p less than 0.005). Despite such negative inotropic effects, cardiac index increased (3.4 +/- 0.7 to 3.9 +/- 0.6 liters/min/m2, p less than 0.02). The time constant of isovolumic relaxation shortened (63 +/- 14 to 47 +/- 9 ms, p less than 0.02); peak filling rate increased (370 +/- 155 to 519 +/- 184 ml/s, p less than 0.001; 2.6 +/- 1.1 to 3.3 +/- 0.9 end-diastolic counts/s, p less than 0.02; and 4.1 +/- 1.6 to 5.5 +/- 1.5 stroke counts/s, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between serum nifedipine concentration and hemodynamic effects in nonobstructive hypertrophic cardiomyopathy.

The relation between nifedipine concentration and hemodynamic effects after sublingual administration of 10 or 20 mg was examined in 13 patients with nonobstructive hypertrophic cardiomyopathy (HC). Serum nifedipine concentrations were determined by gas chromatography and were not related to dose. Peripheral vascular resistance decreased as a function of nifedipine concentration (r = -0.63, p less than 0.001); this was associated with a concentration-related increase in heart rate (r = 0.56, p less than 0.001) and in cardiac index (r = 0.50, p less than 0.001). However, evidence for a pure vasodilator effect of nifedipine was inconsistent, in that the change in stroke volume index with nifedipine was not significant. Although stroke volume index increased at nifedipine concentrations between 60 and 120 ng/ml (38 +/- 6 to 42 +/- 4 ml/m2, p less than 0.01), it decreased at concentrations greater than 120 ng/ml (40 +/- 3 to 38 +/- 4 ml/m2, p less than 0.01). Moreover, pulmonary artery wedge pressure increased at nifedipine concentrations greater than 120 ng/ml (11 +/- 2 to 16 +/- 4 mm Hg, p less than 0.001), suggesting either depressed left ventricular (LV) systolic function or reduced LV filling. To investigate these possible mechanisms, LV systolic and diastolic function was studied during catheterization with a nonimaging scintillation probe in 6 of the 13 patients. In these subjects, heart rate was held constant by atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)