Paolo Bellotti

Clinical Course and Prognosis of Hypertrophic Cardiomyopathy in an Outpatient Population

Hypertrophic cardiomyopathy has been investigated mainly at referral institutions. Thus, the clinical history of the disease that emerges from published studies could be influenced by a bias in patient selection. In the present study, we compared the clinical features of an outpatient population of 25 patients who had hypertrophic cardiomyopathy with those reported in 78 studies published during the past five years. In the 25 study patients, age, sex, and the extent of left ventricular hypertrophy, as well as the prevalence of diastolic filling abnormalities, subaortic obstruction, and ventricular arrhythmias, were similar to those in patients described in the literature. Cardiac symptoms, however, were much less severe in the study patients. Eighteen patients (72 percent) were asymptomatic, six (24 percent) had mild symptoms, and only one (4 percent) had moderate-to-severe symptoms. Of 24 patients followed for a mean period of 4.4 years (range, 2.9 to 5.7), none died or had clinical deterioration. Of 3404 patients described in the 78 studies we reviewed, 2483 (73 percent) came from only two referral institutions. Of the 1721 patients in whom severity of symptoms was reported, 757 (44 percent) had moderate-to-severe symptoms. However, 727 (96 percent) of these patients were studied at one of the same two referral institutions. We conclude that the natural history of hypertrophic cardiomyopathy may be more benign than can be inferred from published reports.

Diastolic abnormalities in patients with hypertrophic cardiomyopathy: relation to magnitude of left ventricular hypertrophy.

To investigate the relationship between diastolic abnormalities and left ventricular hypertrophy, 52 patients with hypertrophic cardiomyopathy (HCM) and 22 normal subjects were studied with digitized M mode echocardiography and two-dimensional echocardiography. Echocardiographic indexes of diastolic function were compared in patients with different extent of left ventricular hypertrophy. Time interval from minimum left ventricular internal dimension to mitral valve opening and time to peak rate of increase in left ventricular internal dimension were significantly prolonged (80 +/- 31 and 100 +/- 37 msec, respectively) in patients with HCM and the most extensive left ventricular hypertrophy compared with those in patients with mild left ventricular hypertrophy (59 +/- 25 and 74 +/- 34 msec, respectively; p less than .01). Furthermore, peak rate of posterior wall diastolic excursion was significantly reduced in those patients with HCM and posterior wall hypertrophy (8.3 +/- 4.0 cm/sec) compared with that in patients with HCM but normal posterior wall thickness (11.2 +/- 3.4 cm/sec; p less than .002). However, abnormal M mode echocardiographic indexes of diastolic function were also identified in a substantial proportion of patients (i.e., 73%) with HCM and only mild left ventricular hypertrophy. In these patients, time interval from minimum left ventricular internal dimension to mitral valve opening (59 +/- 25 msec), peak rate (12 +/- 4 cm/sec), and time to peak rate of increase in left ventricular internal dimension (74 +/- 34 msec) were significantly different from normal (25 +/- 12 msec, 21 +/- 3 cm/sec, and 49 +/- 12 msec, respectively; p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance and natural history of left ventricular thrombi in patients with acute anterior myocardial infarction: a two-dimensional echocardiographic study.

Fifty-eight patients with transmural anterior myocardial infarction were prospectively studied with serial two-dimensional echocardiography to determine the clinical implications and prognostic significance of detection of left ventricular thrombus during acute myocardial infarction, the incidence of systemic embolization, and the possible occurrence of spontaneous regression of left ventricular thrombi. Patients were not treated with anticoagulants or platelet inhibitors during the acute phase of infarction or during follow-up. Two-dimensional echocardiograms were obtained within 24 hr of myocardial infarction, every 24 hr until day 5, every 48 hr until day 15, and every month for a follow-up of 2 to 11 months (mean 7), in the surviving patients; a total of 774 echocardiograms were obtained. Left ventricular thrombi were identified in 24 (41%) of the 58 study patients, and developed within 48 hr of infarction in 11 of these patients. Ten (91%) of the 11 patients with early thrombus formation died during hospitalization or during follow-up, while only two (15%) of the 13 who developed a thrombus after 48 hr of infarction died (p less than .005). Incidence of Killip class III or IV, total lactic dehydrogenase values, and extent of wall motion abnormalities were significantly higher in patients who developed a thrombus within 48 hr of infarction than in patients without thrombus. On the other hand, in patients who developed a thrombus after 48 hr of infarction, these parameters were not significantly different from those in patients who did not develop a thrombus. Spontaneous regression of thrombi was documented in three (20%) of the 15 patients who survived the acute phase of myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous morphologic changes in left ventricular thrombi: a prospective two-dimensional echocardiographic study.

Previous retrospective echocardiographic studies have reported a higher embolic potential of left ventricular thrombi with protruding configuration and patterns of mobility. The present study was performed to prospectively assess the shape and mobility patterns of left ventricular thrombi and their spontaneous changes with time. Two-dimensional echocardiograms were obtained in 109 consecutive patients with acute anterior myocardial infarction within 24 hr of the onset of symptoms, every 24 hr until day 5, every 48 hr until day 15, and then every month for a follow-up of 1 to 29 (mean 14 +/- 8) months in the survivors. None of the patients were treated with anticoagulants or platelet inhibitors during the study period. Left ventricular thrombi, detected in 59 patients (54%), appeared from 1 to 362 (mean 12 +/- 47) days after myocardial infarction. At first detection, the shape was mural in 21 patients and protruding in 38; patterns of mobility were present in eight patients. During follow-up, changes in the shape of the thrombi were noted in 24 patients (41%; from mural to protruding in nine, from protruding to mural in 15). These variations were encountered between 2 and 490 (mean 64 +/- 117) days after the first observation of the thrombus. Patterns of mobility, previously detected in eight patients, disappeared in five of eight within 2 to 28 (mean 14 +/- 11) days.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease: a report from the echo-persantine and echo-dobutamine international cooperative studies

OBJECTIVES This study sought to verify the effectiveness of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease. BACKGROUND Noninvasive prognostic assessment of single-vessel disease is an unresolved issue to date. METHODS The study evaluated prospectively collected data from 754 patients with angiographic single-vessel disease who underwent either dipyridamole (n = 576) or dobutamine (n = 178) stress echocardiography. Invasive treatment (coronary revascularization within 3 months of stress testing) was performed in 260 patients and medical treatment in 494. RESULTS Echocardiographic positivity was observed in 421 patients (56%). Patients treated invasively had a higher incidence of stress test positivity (69% vs. 49%, p < 0.001) and left anterior descending coronary artery involvement (60% vs. 46%, p < 0.001) than patients maintained with medical therapy. During a mean follow-up of 37 months, 54 hard cardiac events occurred (14 deaths, 40 nonfatal infarctions): 37 in medically and 17 in invasively treated patients (7.5% vs. 6.5%, p = NS). On Cox analysis, a positive result on stress testing was the only independent prognostic predictor in medically treated patients (relative risk 2.92, 95% confidence interval 1.29 to 6.59). The 4-year infarction-free survival rate was higher for a negative than a positive stress test result in medically (93.9% vs. 87.3%, p = 0.009) but not invasively treated patients (92.7% vs. 97.1%, p = 0.545). Moreover, a significantly higher 4-year infarction-free survival rate was found in invasively versus medically treated patients with a positive (p = 0.012), but not in those with a negative, stress test result (p = 0.853). CONCLUSIONS Pharmacologic stress echocardiography is effective in risk stratification of single-vessel disease and can accurately discriminate patients in whom coronary revascularization can have the maximal beneficial effect. These findings have a potential favorable impact on the cost-effectiveness of invasive procedures.

Left ventricular thrombus in anterior acute myocardial infarction after thrombolysis. A GISSI-2 connected study.

BackgroundStreptokinase reduces the incidence of left ventricular thrombosis after acute myocardial infarction. However, it is unknown whether a similar effect can be obtained with different thrombolytic agents and whether subcutaneous calcium heparin can have an additional efficacy. Methods and ResultsTo compare the effects of two different thrombolytic agents combined or not with heparin on the incidence and features of left ventricular thrombi and their related embolic events, we performed a GISSI-2 ancillary echocardiographic study (the first echocardiogram obtained within 48 hours of symptoms onset and the second before hospital discharge) that enrolled 180 consecutive patients (mean age, 63 ± 11 years, 142 men) with a first anterior acute myocardial infarction. Patients were randomized into four groups of treatment: recombinant tissue-type plasminogen activator (rt-PA) (n =47), rt-PA plus heparin (n =45), streptokinase (n =39), and streptokinase plus heparin (n =49). Left ventricular thrombosis was observed in 51 of 180 patients (28%). No significant differences were found concerning the incidence of thrombi in the four treatment groups. Mural shape of left ventricular thrombi was found more frequently than the protruding shape (71% versus 29% at the first examination, 64% versus 36% at the second), particularly in heparin-treated patients (93% versus 7% at first examination, 70%o versus 30% at the second). Only one embolic event (0.5%) occurred during the hospitalization. ConclusionsWe conclude that 1) the rate of left ventricular thrombi does not differ in patients with acute myocardial infarction treated either with streptokinase or rt-PA, 2) subcutaneous heparin, when begun 12 hours after intravenous thrombolysis, does not appear to further reduce the occurrence of thrombi but seems to influence the shape of left ventricular thrombi, and 3) during the predischarge period, embolic events are rare in patients treated by thrombolysis.

Noninvasive assessment of left ventricular diastolic function: Comparative analysis of pulsed Doppler ultrasound and digitized M-mode echocardiography

The relation between Doppler and digitized M-mode echocardiographic indexes of left ventricular (LV) diastolic function was analyzed. Diastolic variables obtained with these 2 techniques were compared in 19 normal volunteers and in 25 patients with a variety of cardiac diseases. The 2 techniques were in agreement in distinguishing normal from abnormal diastolic function in 20 of the 25 patients (80%) with cardiac disease. Furthermore, a close linear relation with a high correlation coefficient and a small standard error of the estimate was identified between measurements of isovolumic relaxation determined by Doppler and by M-mode echocardiography (r = 0.82, standard error of the estimate = 18 ms). Doppler indexes of diastolic filling such as the slope (descent) and the duration of the early diastolic flow-velocity peak did not show a close correlation with the peak rate and the time to peak rate of increase in LV internal dimension determined by digitized echocardiography. Thus, Doppler and digitized echocardiography were consistent in distinguishing normal from abnormal diastolic function in most of the study patients, although specific variables of LV ventricular filling determined by the 2 techniques were not closely related. In addition, Doppler and M-mode echocardiographic measurements of isovolumic relaxation showed an excellent correlation.

Left Atrial Appendage Function Assessed by Transesophageal Echocardiography Before and on the Day After Elective Cardioversion for Nonvalvular Atrial Fibrillation

We investigated left atrial appendage function by transesophageal echocardiography, on the day after external electrical cardioversion to sinus rhythm, in 41 patients with nonvalvular atrial fibrillation. After cardioversion, appendage contraction synchronized with the electrical and mechanical activity of the atrium, which was restored in about 70% of the patients.

Quantitative ultrasonic analysis of myocardium in patients with thalassemia major and iron overload.

BackgroundPatients with f-thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac dysfunction has been documented even in thalassemics without clinical manifestations of heart failure as well as by conventional echocardiographic-Doppler techniques. The purpose of this study was to assess the acoustic quantitative properties of myocardium in patients with iron overload. Methods and ResultsThirty-eight patients with (3-thalassemia major, without clinical signs of cardiac failure, and 20 age- and sex-matched young controls were studied by echocardiography. An on-line analysis of the ultrasonic radiofrequency signal was performed to obtain quantitative operator-independent measurements of the integrated backscatter (IB) signal of the ventricular septum and the posterior wall. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent (IB%). Thalassemic patients had been receiving transfusion therapy for 16±5 years and had received 313±+138 transfusion units; they all had received chelation treatment (desferroxiamine) for 9±2 years. Patients and controls showed comparable values of echocardiographically assessed percent fractional shortening (32±3% versus 36±4%, p=NS), whereas thalassemics showed higher values of left ventricular mass index (118±30 versus 98 ± 15 g/m2, p<0.05). The IB% values were higher in patients with thalassemia major than in controls for both septum (35±14% versus 21+6%, p<0.001) and posterior wall (16±6% versus 11±3%, p<0.001). In thalassemic patients, no significant correlation was found between the septum IB% value and hematological parameters, such as the total number of transfusions (r=0.2, p=NS) or the mean ferritin value (r=0.1, p=NS). No significant correlation was also found between the septum IB% value and the echocardiographically assessed left ventricular mass index (r=0.2, p=NS). ConclusionThese data demonstrate that myocardial reflectivity is abnormally increased in patients with thalassemia major under transfusion treatment, probably due to myocardial iron deposits and/or secondary structural changes. These quantitatively assessed abnormalities in regional reflectivity can be detected when conventional echocardiographic parameters of systolic left ventricular function are undistinguishable from normal controls.

Long-term prospective assessment of left ventricular thrombus in anterior wall acute myocardial infarction and implications for a rational approach to embolic risk

To prospectively assess the predictive value of left ventricular (LV) thrombus anatomy for defining the embolic risk after acute myocardial infarction (AMI), 2 comparable groups of patients with a first anterior AMI (group A, 97 thrombolysed patients; group B, 125 patients untreated with antithrombotic drugs [total 222]) underwent prospective serial echocardiography (follow-up 39 +/- 13 months) at different time periods. LV thrombi were detected in 26 patients in group A (27%) and in 71 in group B (57%; p <0.005). Embolism occurred in 12 patients (5.4%; 1 in group A [1%] vs 11% in group B [9%], p < 0.04). At multivariate analysis, thrombus morphologic changes were the most powerful predictor of embolism (p <0.001), followed by protruding shape (p <0.01) and mobility (p <0.02). In patients untreated with thrombolysis, a higher occurrence of thrombus morphologic changes (48% vs 8%, p <0.002) and protruding shape (69% vs 31%, p <0.002) were observed, whereas thrombus mobility was similar in the 2 groups (18% vs 8%, p = NS). Thrombus resolution occurred more frequently in thrombolysed patients (85% vs 56%, p <0.002). Thus, after anterior AMI, changes in LV thrombus anatomy frequently occur and appear the most powerful predictor of embolization. A minor prevalence of thrombus, a more favorable thrombus anatomy, and a higher resolution rate may contribute to reduce embolic risk after thrombolysis.