Francesco Chiarella

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.

Prognostic value of dipyridamole echocardiography early after uncomplicated myocardial infarction: A large-scale, multicenter trial

PURPOSE To determine the prognostic capability of the dipyridamole echocardiography test (DET) early after an acute myocardial infarction. PATIENTS AND METHODS On the basis of 11 different echocardiographic laboratories, all with established experience in stress echocardiography and fulfilling quality-control requirements for stress echocardiographic readings, 925 patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. RESULTS During the follow-up, there were 34 deaths and 37 nonfatal myocardial infarctions; 104 patients developed class III or IV angina and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction, and death), the most important univariate predictor was the presence of an inducible wall motion abnormality after dipyridamole administration (chi 2 = 45.8). With a Cox analysis, echocardiographic positivity, age, and male gender were found to have an independent and additive value. Considering survival (and, therefore, death as the only event), age was the most meaningful parameter, followed by the wall motion score index during dipyridamole administration (chi 2 = 12.1). Among other parameters, the resting wall motion score index was a significant predictor of death. In a multivariate analysis, the prognostic contributions of age (relative risk estimate = 1.08) and wall motion score index during dipyridamole administration (relative risk estimate = 4.1) were independent and additive. In particular, considering death only, the event rate was 2% in patients with negative DET results, 4% in patients with positive high-dose DET results, and 7% in patients with positive low-dose DET results. CONCLUSIONS DET is feasible and safe early after uncomplicated myocardial infarction and allows effective risk stratification on the basis of the presence, severity, extent, and timing of the induced dyssynergy.

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)

Safety of intravenous high-dose dipyridamole echocardiography

Abstract Clinical data on 10,451 high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole-echocardiography tests (DET) performed in 9,122 patients were prospectively collected from 33 echocardiographic laboratories, each contributing >100 tests. All patients were studied for documented or suspected coronary artery disease (1,117 early [

Epidemiology of acute myocardial infarction in the Italian CCU network: the BLITZ study.

AIMS A large number of descriptive data on patients with acute myocardial infarction are based on clinical trials and registries on non consecutive patients: these data may give only a partial picture on treatment delay, patient characteristics, treatment and outcome of acute myocardial infarction in the real world. METHODS AND RESULTS The BLITZ survey prospectively enrolled all of the patients with acute myocardial infarction admitted in 296 (87%) Italian Coronary Care Units from 15-29 October 2001. Data on treatment delay, therapeutic strategies, duration of hospitalization and 30-day outcome were collected. One thousand nine hundred and fifty-nine consecutive patients (mean age 67+/-12 years, 70% males) were enrolled, 65% with ST-segment elevation (STEMI), 30% with no ST-segment elevation (NSTEMI) and 5% with undetermined ECG. The median delay between symptom onset and hospital arrival was 2h and 9 min with 76% of patients hospitalized within the sixth hour (26% within the first hour, 48% within the second). The median delay from hospital arrival to reperfusion therapy in STEMI was 45 min (IQR 26-85) for thrombolysis (50% of the patients) and 85 min (IQR 60-135) for primary angioplasty (15% of the patients). Coronary angiography was performed during hospital stay in 46% of the patients (STEMI 48%, NSTEMI 43%, undetermined AMI 35%), coronary angioplasty in 25% (STEMI 26%, NSTEMI 15%, undetermined AMI 13%) and coronary bypass in 1.4% (1%, 2.2% and 1% respectively). Twenty-two percent of the patients admitted to hospitals without cath-lab were transferred to a tertiary care hospital for invasive procedures. The overall median hospital stay was 10 days (IQR 7-12, STEMI 10, NSTEMI 9, undetermined AMI 11) and was not significantly different between hospitals with or without cath-lab (respectively, 9 and 10 days, P=0.38). After discharge and up to 30 days, coronary angiography was performed in 11% (STEMI 11%, NSTEMI 11%, undetermined MI 9%), angioplasty in 10% (STEMI 10%, NSTEMI 11%, undetermined MI 7%), bypass surgery in 7% (STEMI 5%, NSTEMI 11%, undetermined AMI 7%). The in-hospital and 30-day case fatality rates were 7.4% and 9.4%, respectively (7.5% and 9.5% for STEMI, 5.2% and 7.1% for NSTEMI, 18.2% and 21.2% for undetermined MI). CONCLUSIONS Patients with acute myocardial infarction admitted to the Italian CCUs, are older than those represented in clinical trials. A high proportion of these cases has the chance to receive early reperfusion therapy. Short-term mortality is lower than expected for patients with STEMI, but higher than reported for NSTEMI.

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)

Predischarge Two-Dimensional Echocardiographic Evaluation of Left Ventricular Thrombosis After Acute Myocardial Infarction in the GISSI-3 Study

Left ventricular (LV) thrombosis can be found in patients with acute myocardial infarction (AMI). No wide multicenter trial on AMI has provided information about LV thrombosis until now. The protocol of the GISSI-3 study included the search for the presence of LV thrombosis in patients from 200 coronary care units that did not specifically focus on LV thrombosis. We examined the GISSI-3 database results related to 8,326 patients at low to medium risk for LV thrombi in which a predischarge echocardiogram (9 +/- 5 days) was available. LV thrombosis was found in 427 patients (5.1%): 292 of 2,544 patients (11.5%) with anterior AMI and in 135 of 5,782 patients (2.3%) with AMI in other sites (p <0.0001). The incidence of LV thrombosis was higher in patients with ejection fraction < or = 40% (151 of 1,432 [10.5%] vs 276 of 6,894 [4%]; p <0.0001) both in the total population and in the subgroup with anterior AMI (106 of 597 [17.8%] vs 186 of 1,947 [9.6%]; p <0.0001). Multivariate analysis showed that only the Killip class > I and early intravenous beta-blocker administration were independently associated with higher LV thrombosis risk in the subgroup of patients with anterior AMI (odds ratio 1.75, 95% confidence interval 1.28 to 2.39; odds ratio 1.32, 95% confidence interval 1.02 to 1.72, respectively). In patients with anterior AMI, oral beta-blocker therapy given or not given after early intravenous beta-blocker administration does not influence the occurrence of LV thrombosis. The rate of LV thrombosis was similar in patients treated or not treated with nitrates and lisinopril both in the total population and in patients with anterior and nonanterior AMI. In conclusion, in the GISSI-3 population at low to medium risk for LV thrombi, the highest rate of occurrence of LV thrombosis was found among patients with anterior AMI and an ejection fraction < 40%. Killip class > I and the early intravenous beta-blocker administration were the only variables independently associated with a higher predischarge incidence of LV thrombosis after anterior AMI.

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)

Current presentation and management of 7148 patients with atrial fibrillation in cardiology and internal medicine hospital centers: the ATA AF study.

BACKGROUND Atrial fibrillation (AF) is associated with a high risk of stroke and mortality. AIMS To describe the difference in AF management of patients (pts) referred to Cardiology (CARD) or Internal Medicine (MED) units in Italy. METHODS AND RESULTS From May to July 2010, 360 centers enrolled 7148 pts (54% in CARD and 46% in MED). Median age was 77 years (IQR 70-83). Hypertension was the most prevalent associated condition, followed by hypercholesterolemia (28.9%), heart failure (27.7%) and diabetes (24.3%). MED pts were older, more frequently females and more often with comorbidities than CARD pts. In the 4845 pts with nonvalvular AF, a CHADS2 score ≥ 2 was present in 53.0% of CARD vs 75.3% of MED pts (p<.0001). Oral anticoagulants (OAC) were prescribed in 64.2% of CARD vs 46.3% of MED pts (p<.0001); OAC prescription rate was 49.6% in CHADS2 0 and 56.2% in CHADS2 score ≥ 2 pts. At the adjusted analysis patients managed in MED had a significantly lower probability to be treated with OAC. Rate control strategy was pursued in 51.4% of the pts (60.5% in MED and 43.6% in CARD) while rhythm control was the choice in 39.8% of CARD vs 12.9% of MED pts (p<.0001). CONCLUSIONS Cardiologists and internists seem to manage pts with large epidemiological differences. Both CARD and MED specialists currently fail to prescribe OAC in accordance with stroke risk. Patients managed by MED specialists have a lower probability to receive an OAC treatment, irrespective of the severity of clinical conditions.

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.