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P Spirito

Publications and source records attributed to P Spirito.

At least 19 recordsLinked to original sources
PubMed2001

[Hypertrophic cardiomyopathy and sudden death].

Hypertrophic cardiomyopathy is a primary and usually familial cardiac disorder characterized by a genetic, pathophysiologic and clinical complexity. The natural history of the disease is extremely heterogenous: many patients have no or mild symptoms and a near-normal longevity, some develop severe symptoms of heart failure, and others die suddenly often at a young age and in the absence of previous symptoms. Although sudden and unexpected cardiac death may occur at any age in hypertrophic cardiomyopathy, this devastating event is the most common modality of death in children and young patients. Despite intense investigation, risk stratification remains a major challenge. This paper examines the present knowledge on risk assessment and treatment strategies for the prevention of sudden death.

Cardiomyopathy, Hypertrophic↗
PubMed2000

Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non-referral-based patient population.

BACKGROUND: Death resulting from hypertrophic cardiomyopathy (HCM), particularly when sudden, has been reported to be largely confined to young persons. These data emanated from tertiary HCM centers with highly selected referral patterns skewed toward high-risk patients. METHODS AND RESULTS: The present analysis was undertaken in an international population of 744 consecutively enrolled and largely unselected patients more representative of the overall HCM spectrum. HCM-related death occurred in 86 patients (12%) over 8+/-7 years (mean+/-SD). Three distinctive modes of death were as follows: (1) sudden and unexpected (51%; age, 45+/-20 years); (2) progressive heart failure (36%; age, 56+/-19 years); and (3) HCM-related stroke associated with atrial fibrillation (13%; age, 73+/-14 years). Sudden death was most common in young patients, whereas heart failure- and stroke-related deaths occurred more frequently in midlife and beyond. However, neither sudden nor heart failure-related death showed a statistically significant, disproportionate age distribution (P=0.06 and 0.5, respectively). Stroke-related deaths did occur disproportionately in older patients (P=0.002). Of the 45 patients who died suddenly, most (71%) had no or mild symptoms, and 7 (16%) participated in moderate to severe physical activities at the time of death. CONCLUSIONS: HCM-related cardiovascular death occurred suddenly, or as a result of heart failure or stroke, largely during different phases of life in a prospectively assembled, regionally based, and predominantly unselected patient cohort. Although most sudden deaths occurred in adolescents and young adults, such catastrophes were not confined to patients of these ages and extended to later phases of life. This revised clinical profile suggests that generally held epidemiological tenants for HCM have been influenced considerably by skewed reporting from highly selected populations. These data are likely to importantly affect risk stratification and treatment strategies importantly for the prevention of sudden death in HCM.

Adolescent↗
PubMed2000

Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy.

BACKGROUND: Sudden death is known to be a possible consequence of hypertrophic cardiomyopathy. Quantification of the risk of sudden death, however, remains imprecise for most patients with this disease. METHODS: We assessed the relation between the magnitude of left ventricular hypertrophy and mortality in 480 consecutive patients with hypertrophic cardiomyopathy. The patients were categorized into five subgroups according to maximal wall thickness: 15 mm or less, 16 to 19 mm, 20 to 24 mm, 25 to 29 mm, and 30 mm or more. Their ages ranged from 1 to 89 years (median, 47). RESULTS: Over a mean follow-up period of 6.5 years, 65 of the 480 patients (14 percent) died: 23 suddenly, 15 of heart failure, and 27 of noncardiac causes or stroke. The risk of sudden death increased progressively and in direct relation to wall thickness (P=0.001), ranging from 0 per 1000 person-years (95 percent confidence interval, 0 to 14.4) for a wall thickness of 15 mm or less to 18.2 per 1000 person-years (95 percent confidence interval, 7.3 to 37.6) for a wall thickness of 30 mm or more and almost doubling from each wall-thickness subgroup to the next. The cumulative risk 20 years after the initial evaluation was close to zero for patients with a wall thickness of 19 mm or less but almost 40 percent for wall thicknesses of 30 mm or more. As compared with the other subgroups, patients with extreme hypertrophy were the youngest (mean age, 31 years), and most (41 of 43) had mild symptoms or no symptoms; of the 12 patients who were less than 18 years old at the initial evaluation, 5 died suddenly. CONCLUSIONS: In hypertrophic cardiomyopathy, the magnitude of hypertrophy is directly related to the risk of sudden death and is a strong and independent predictor of prognosis. Young patients with extreme hypertrophy, even those with few or no symptoms, appear to be at substantial long-term risk and deserve consideration for interventions to prevent sudden death. The majority of patients with mild hypertrophy are at low risk and can be reassured regarding their prognosis.

Adolescent↗
PubMed2000

Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease associated with a risk of ventricular tachyarrhythmias and sudden death, especially in young patients. METHODS: We conducted a retrospective multicenter study of the efficacy of implantable cardioverter-defibrillators in preventing sudden death in 128 patients with hypertrophic cardiomyopathy who were judged to be at high risk for sudden death. RESULTS: At the time of the implantation of the defibrillator, the patients were 8 to 82 years old (mean [+/-SD], 40+/-16), and 69 patients (54 percent) were less than 41 years old. The average follow-up period was 3.1 years. Defibrillators were activated appropriately in 29 patients (23 percent), by providing defibrillation shocks or antitachycardia pacing, with the restoration of sinus rhythm; the average age at the time of the intervention was 41 years. The rate of appropriate defibrillator discharge was 7 percent per year. A total of 32 patients (25 percent) had episodes of inappropriate discharges. In the group of 43 patients who received defibrillators for secondary prevention (after cardiac arrest or sustained ventricular tachycardia), the devices were activated appropriately in 19 patients (11 percent per year). Of 85 patients who had prophylactic implants because of risk factors (i.e., for primary prevention), 10 had appropriate interventions (5 percent per year). The interval between implantation and the first appropriate discharge was highly variable but was substantially prolonged (four to nine years) in six patients. In all 21 patients with stored electrographic data and appropriate interventions, the interventions were triggered by ventricular tachycardia or fibrillation. CONCLUSIONS: Ventricular tachycardia or fibrillation appears to be the principal mechanism of sudden death in patients with hypertrophic cardiomyopathy. In high-risk patients with hypertrophic cardiomyopathy, implantable defibrillators are highly effective in terminating such arrhythmias, indicating that these devices have a role in the primary and secondary prevention of sudden death.

Adolescent↗
PubMed1999

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.

Acute Disease↗
PubMed1998

Implications of left ventricular remodeling in hypertrophic cardiomyopathy.

Left ventricular remodeling occurs spontaneously among patients with hypertrophic cardiomyopathy in several ways: (1) wall thickening in children; (2) wall thinning associated with cavity enlargement in midlife; and possibly (3) a very gradual wall thinning process occurring over long periods of time in adulthood.

Adolescent↗
PubMed1998

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.

Adult↗
PubMed1997

Clinical features of hypertrophic cardiomyopathy caused by mutation of a "hot spot" in the alpha-tropomyosin gene.

OBJECTIVES: We studied the clinical and genetic features of familial hypertrophic cardiomyopathy (FHC) caused by an Asp175Asn mutation in the alpha-tropomyosin gene in affected subjects from three unrelated families. BACKGROUND: Correlation of genotype and phenotype has provided important information in FHC caused by beta-cardiac myosin and cardiac troponin T mutations. Comparable analyses of hypertrophic cardiomyopathy caused by alpha-tropomyosin mutations have been hampered by the rarity of these genetic defects. METHODS: The haplotypes of three kindreds with FHC due to an alpha-tropomyosin gene mutation, Asp175Asn, were analyzed. The cardiac histopathologic findings of this mutation are reported. Distribution of left ventricular hypertrophy in affected members was assessed by two-dimensional echocardiography, and patient survival rates were compared. RESULTS: Genetic studies defined unique haplotypes in the three families, demonstrating that independent mutations caused the disease in each. The Asp175Asn mutation caused cardiac histopathologic findings of myocyte hypertrophy, disarray and replacement fibrosis. The severity and distribution of left ventricular hypertrophy varied considerably in affected members from the three families (mean maximal wall thickness +/- SD: 24 +/- 4.5 mm in anterior septum of Family DT; 15 +/- 2.7 mm in anterior septum and free wall of Family DB; 18 +/- 2.1 mm in posterior septum of Family MI), but survival was comparable and favorable. CONCLUSIONS: Nucleotide residue 579 in the alpha-tropomyosin gene may have increased susceptibility to mutation. On cardiac histopathologic study, defects in this sarcomere thin filament component are indistinguishable from other genetic etiologies of hypertrophic cardiomyopathy. The Asp175Asn mutation can elicit different morphologic responses, suggesting that the hypertrophic phenotype is modulated not by genetic etiologic factors alone. In contrast, prognosis reflected genotype; near normal life expectancy is found in hypertrophic cardiomyopathy caused by the alpha-tropomyosin mutation Asp175Asn.

Adolescent↗
PubMed1997

Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families.

The diagnosis of hypertrophic cardiomyopathy has relied on echocardiographic demonstration of unexplained left ventricular hypertrophy. The prevalence of hypertrophic cardiomyopathy defined in this way has been estimated to be 1:500 and experience indicates that these criteria are relatively specific when other causes of left ventricular hypertrophy are absent. In recent years, however, the systematic evaluation of pedigrees performed in the context of molecular genetic studies revealed that in some families with hypertrophic cardiomyopathy up to 20% of adults who carry a disease causing gene defect do not fulfil conventional echocardiographic criteria. None the less, most of these individuals show symptoms, electrocardiographic alterations, and/or minor echocardiographic abnormalities. Revised diagnostic criteria in members of families with hypertrophic cardiomyopathy are proposed, including major and minor criteria based on symptoms, and electrocardiographic and echocardiographic abnormalities. Given that the chance of inheriting the gene defect is 1:2, the likelihood that symptoms plus electrocardiographic or echocardiographic abnormalities are the expression of a disease causing gene is high.

Adult↗
PubMed1996

Changes in effective aortic valve area during ejection in adults with aortic stenosis.

Measurements of valve orifice area in aortic stenosis are based on the assumption that orifice area remains constant throughout ejection and is independent of transvalvular gradients and flow. Recent studies, however, have suggested that the calculated valve area of calcific aortic stenosis may change in different flow conditions. Therefore, we tested the hypothesis that in vivo effective orifice area of a stenotic aortic valve changes continuously during ejection, which would make a single area measurement a potentially inadequate indicator of the severity of the stenosis. Doppler measurements of flow velocity in the ascending aorta and in the left ventricular outflow tract at peak velocity, at half-peak velocity during acceleration (midacceleration), and at half-peak velocity during deceleration (mid-deceleration) were obtained in 26 patients with aortic stenosis (mean gradient 50 +/- 19 mm Hg and effective aortic orifice are 0.7 +/- 0.3 dcm2) and in 14 normal subjects of similar age and gender, to calculate instantaneous effective aortic orifice area at midacceleration, at peak velocity and at mid-deceleration. In the 26 patients with aortic stenosis, aortic valve area at midacceleration was 84 +/- 15% of valve area at peak velocity (p < 0.0001), and valve area at mid-deceleration was 113 +/- 17% of that measured at peak velocity (p < 0.01). Conversely, in normal subjects, aortic valve area remained constant during ejection and was 97 +/- 5% and 99 +/- 6% of valve area at peak velocity, respectively, at midacceleration and mid-deceleration (p > 0.05). In addition, in patients with aortic stenosis the percentage of change in effective aortic valve area from midacceleration to mid-deceleration varied widely, from -17% to +49% (mean change +26 +/- 14%). There was no relation between percentage of change in effective valve area and mean transaortic gradient (r = 0.05; p = 0.30) or effective valve area at peak velocity (r = -0.11; p = 0.14). Our results indicate that effective aortic valve area continues to change during ejection in patients with aortic stenosis, and that the magnitude of this change is independent of the usual indexes of severity of the stenosis. Conversely, effective aortic valve area remains constant during ejection in normal subjects.

Aged↗
PubMed1995

A de novo mutation in alpha-tropomyosin that causes hypertrophic cardiomyopathy.

BACKGROUND: Two missense mutations in the gene for alpha-tropomyosin have been described that segregate with hypertrophic cardiomyopathy in single families. To confirm that these mutations are the cause of the disease, we have investigated the origins of one of these mutations, Asp175Asn, in a third and unrelated family. METHODS AND RESULTS: The presence or absence of an alpha-tropomyosin mutation and the haplotypes of the flanking chromosomal regions were determined for members of a family with hypertrophic cardiomyopathy. Haplotypes were constructed by use of an intragenic polymorphism and 10 flanking polymorphisms spanning a region of 35 centimorgans. The Asp175Asn missense mutation was present in the proband and his two affected offspring but not in any of the proband's three siblings. Although both parents were deceased, the haplotypes of the four parental chromosomes could be reconstructed. One parental chromosome was transmitted to two offspring: one bearing the Asp175Asn mutation (the affected proband) and one clinically unaffected sibling who lacked the alpha-tropomyosin mutation. Thus, the Asp175Asn mutation must have arisen de novo. CONCLUSIONS: De novo mutations in the alpha-tropomyosin gene can result in hypertrophic cardiomyopathy that may appear to be sporadic but in subsequent generations gives rise to familial disease. Individuals with sporadic hypertrophic cardiomyopathy should be advised of the risk of transmission to offspring. In addition, these findings provide the strongest genetic evidence that mutations in the alpha-tropomyosin gene are directly responsible for hypertrophic cardiomyopathy.

Adolescent↗
PubMed1995

Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy can be caused by mutations in the genes for beta cardiac myosin heavy chain, alpha-tropomyosin, or cardiac troponin T. It is not known how often the disease is caused by mutations in the tropomyosin and troponin genes, and the associated clinical phenotypes have not been carefully studied. METHODS: Linkage between polymorphisms of the alpha-tropomyosin gene or the cardiac troponin T gene and hypertrophic cardiomyopathy was assessed in 27 families. In addition, 100 probands were screened for mutations in the alpha-tropomyosin gene, and 26 were screened for mutations in the cardiac troponin T gene. Life expectancy, the incidence of sudden death, and the extent of left ventricular hypertrophy were compared in patients with different mutations. RESULTS: Genetic analyses identified only one alpha-tropomyosin mutation, identical to one previously described. Five novel mutations in cardiac troponin were identified, as well as a further example of a previously described mutation. The clinical phenotype of four troponin T mutations in seven unrelated families was similar and was characterized by a poor prognosis (life expectancy, approximately 35 years) and a high incidence of sudden death. The mean (+/- SD) maximal thickness of the left ventricular wall in subjects with cardiac troponin T mutations (16.7 +/- 5.5 mm) was significantly less than that in subjects with beta cardiac myosin heavy-chain mutations (23.7 +/- 7.7 mm, P < 0.001). CONCLUSIONS: Mutations in alpha-tropomyosin are a rare cause of familial hypertrophic cardiomyopathy, accounting for approximately 3 percent of cases. Mutations in cardiac troponin T account for approximately 15 percent of cases of familial hypertrophic cardiomyopathy in this referral-center population. These mutations are characterized by relatively mild and sometimes subclinical hypertrophy but a high incidence of sudden death. Genetic testing may therefore be especially important in this group.

Adolescent↗