Giulio Rizzoli

Arrhythmogenic right ventricular cardiomyopathy in young versus adult patients : similarities and differences

OBJECTIVES This study was designed to evaluate and compare the patterns of arrhythmogenic right ventricular cardiomyopathy in young people and adults. BACKGROUND Few data are available on this cardiomyopathy in young people because clinical and morphologic findings considered pathognomonic are normally based on observations in adults. However, a familial occurrence with a probable genetic transmission led to the study of children and to early detection of this disease, in which sudden death has been reported even in young people. METHODS Seventeen young patients with arrhythmogenic right ventricular cardiomyopathy diagnosed at a mean age +/- SD of 14.9 +/- 4.9 years were studied. Clinical, electrocardiographic, echocardiographic, cineangiographic and biopsy findings were compared with those of 19 adult patients whose condition was diagnosed at a mean age of 38.1 +/- 13.4 years. RESULTS Syncope occurred in 23.5% of the young patients but in none of the adults (odds ratio of familial sudden death 5.54, p = 0.1). Ventricular couplets (odds ratio 16.0, p = 0.004) and subtricuspid bulging on echocardiography (odds ratio 5.95, p = 0.036) were prevalent in the young group. Cineangiographic data in the two groups were similar, except that more hypokinetic areas were found in adults (odds ratio 4.44, p = 0.05). Morphometric analysis of biopsy sections showed a greater amount of fibrous tissue in the young patients (p = 0.04) and a prevalence of fatty tissue in the adults (odds ratio 12, p = 0.005). During an equivalent follow-up time (mean 7 years), two young patients died suddenly, and two had ventricular fibrillation in the absence of antiarrhythmic therapy. CONCLUSIONS The pathognomonic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy in adults are also valid for young people. Sudden or aborted death occurred frequently in young untreated patients.

Does the use of bilateral internal mammary artery (IMA) grafts provide incremental benefit relative to the use of a single IMA graft? A meta-analysis approach

OBJECTIVES Does the use of bilateral internal mammary artery (IMA) grafts provide incremental benefit relative to the use of a single IMA graft? METHODS Meta-analysis by qualitative and quantitative protocol of the studies published in the literature in the last 15 years. Only eight, out of 149 observational studies found, met our criteria: surgical results of bilateral versus single IMA, patient age range from 20 to 89 years, exclusion of emergency and diabetic patients, study group larger than 100 patients, minimal follow-up time. The final sample size included 16362 patients. RESULTS Late survival was evaluated at 5 and 10 years. The hazard ratio (HR) was calculated from seven studies, the difference of survival was from six and five studies, respectively. The effect size was summarized using a random effect model, suggested by the results of statistical test for homogeneity of the HR (P < 0.05) and of the survival difference at 5 (P < 0.05) and at 10 years (P < 0.05). The bilateral IMA estimate of combined HR was 0.79 (95% confidence limits, C.L. = 0.66/0.91). The combined difference of survival probability at 5 years was 0.014 (95% C.L. = -0.03/0.06) and at 10 years was 0.07 (95% C.L. = 0.003/0.170). CONCLUSION There is significant evidence in favor of decreasing death risk of bilateral versus single IMA procedure.

Diagnostic accuracy of right ventriculography in arrhythmogenic right ventricular cardiomyopathy.

Diagnostic sensitivity and specificity of cineangiography were evaluated by multivariate logistic discriminant analysis in 32 patients with arrhythmogenic right ventricular (RV) cardiomyopathy, 27 patients with biventricular dilated cardiomyopathy, 28 patients with atrial septal defect and 18 normal subjects. In patients with arrhythmogenic RV cardiomyopathy and biventricular dilated cardiomyopathy, the diagnosis was confirmed by endomyocardial biopsy. All RV values overlapped for the diagnosis of atrial septal defect and arrhythmogenic RV cardiomyopathy; overlapping extended to dilated cardiomyopathy for end-diastolic volume and infundibular dimensions. RV ejection fraction appeared reduced in all the diseases; in particular, mean values in dilated cardiomyopathy and arrhythmogenic RV cardiomyopathy were 38 and 53%, respectively (p less than 0.05). Left ventricular quantitative studies showed a significant difference between dilated and arrhythmogenic RV cardiomyopathy, both in terms of pumping indexes (mean end-diastolic volumes 180 vs 91 ml/m2 and mean ejection fraction 33 vs 60%), and indexes of contractility (stress/end-diastolic volume 3.7 vs 6.7). Multivariate analysis disclosed that transversally arranged hypertrophic trabeculae, separated by deep fissures, were associated with the highest probability of arrhythmogenic RV cardiomyopathy (p less than 0.001). Posterior subtricuspid and anterior infundibular wall bulgings were the only other independently significant variables. Coexistence of these signs was associated with 96% specificity and 87.5% sensitivity. Thus, arrhythmogenic RV cardiomyopathy presents quantitative volumetric and hemodynamic as well as qualitative features that clearly distinguish it from dilated cardiomyopathy and confirm its nosographic autonomy among the primary diseases of the myocardium.

Correlation between cardiac involvement and CTG trinucleotide repeat length in myotonic dystrophy

OBJECTIVES Because sudden death due to complete atrioventricular (AV) block or ventricular arrhythmias is the most dramatic event in myotonic dystrophy, we assessed the relation of cardiac disease to cytosine-thymine-guanine (CTG) triplet mutation in adults affected with myotonic dystrophy. BACKGROUND The myotonic dystrophy mutation, identified as an unstable deoxyribonucleic acid (DNA) sequence (CTG) prone to increase the number of trinucleotide repeats, produces clinical manifestations of the disease in skeletal muscle, the heart and many organ systems. METHODS Forty-two adult patients underwent electrocardiography and echocardiography; in addition, signal-averaging electrocardiography was performed in 22, and 24-h Holter monitoring was recorded in 32. The diagnosis was established by neurologic examination, electromyography, muscle biopsy and DNA analysis. The patients were then classified into three subgroups on the basis of the number of CTG trinucleotide repeat expansions: E1 = 18 patients with 0 to 500 CTG repeats; E2 = 12 patients with up to 1,000 repeats; E3 + E4 = 10 patients with up to 1,500 repeats and 2 patients with > 1,500 repeats. RESULTS The incidence of normal electrocardiographic (ECG) results was found to be significantly different in the three subgroups (55%, 50%, 17% in E1, E2, E3, + E4, respectively, p = 0.04), with the highest values in the group with fewer repeat expansions. The incidence of complete left bundle branch block was also significantly different among the groups (5% in E1, 0% in E2, 42% in E3 + E4 p = 0.01) and was directly correlated with the size of the expansion. A time-domain analysis of the signal-averaged ECG obtained in 12 patients in E1, 4 in E2, 5 in E3 and 1 in E4 showed that abnormal ventricular late potentials were directly correlated with CTG expansion (33% in E1, 75% in E2, 83% in E3 + E4, p = 0.05). Moreover, the incidence of ventricular couplets or triplets showed a positive correlation with size of CTG expansion (0 in E1, 0 in E2, 29% in E3 + E4, chi square 0.02). CONCLUSIONS Our findings suggest that the involvement of specialized cardiac tissue, accounting for severe AV and intraventricular conduction defects, is related to CTG repeat length. In addition, the presence of abnormal late potentials directly correlates to CTG expansion. Abnormal late potentials, caused by slowed and fragmented conduction through damaged areas of myocardium, represent a substrate for malignant reentrant ventricular arrhythmias. In the future, therefore, molecular analysis of DNA should identify patients with cardiac disease at high risk for development of AV block or lethal ventricular arrhythmias.

Late potentials and ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

We studied 38 patients (mean age 32 +/- 14 years) with arrhythmogenic right ventricular cardiomyopathy (ARVC) to evaluate the clinical significance of histologic features on endomyocardial biopsy specimens as related to signal-averaged electrocardiography (SAECG), spontaneous ventricular arrhythmias, and hemodynamic features. Fifteen patients presented with ventricular tachycardia or fibrillation (sustained ventricular arrhythmias), 23 with other minor arrhythmias. SAECG variables and right ventricular ejection fraction (RVEF) were statistically correlated with the extent of myocardial fibrosis on biopsy in ARVC. An increased percentage of fibrous tissue (> or = 30%) was a significant univariate predictor of late potentials (p = 0.004) and reduced RVEF (p = 0.02). The 18 patients with late potentials had an increased percentage of fibrous tissue (p = 0.01), a reduced RVEF (p = 0.0004), and a higher risk for sustained ventricular arrhythmias (p = 0.05) than the 20 patients without late potentials. RVEF was the most powerful predictor of late potentials (p = 0.004) at multivariate analysis. Moreover, RVEF < or = 50% was associated with an increased risk for development of sustained ventricular arrhythmias (p = 0.02). A SAECG parameter, namely the root-mean-square voltage of the terminal 40 ms at 25 Hz, was an independent predictive factor for the occurrence of sustained ventricular arrhythmias (p = 0.02). Although fibrous tissue may contribute to delayed myocardial activation in ARVC, a reduced RVEF plays an essential role for spontaneous manifestation of sustained ventricular arrhythmias.

Reoperations for acute prosthetic thrombosis and pannus: an assessment of rates, relationship and risk.

OBJECTIVE Mechanical valvular prostheses have the advantage of longevity but carry a risk of thrombosis which is dependant on valve design, materials and host-related interface. While pannus is common to both biologic and mechanical valves, acute prosthetic thrombosis is mostly a complication of mechanical valves; therefore we investigated to find rates and risk of these obstructive complications. METHODS Between 1/1/70 and 31/12/97, 2680 patients received at least one mechanical prosthesis in the aortic or mitral or tricuspid position and a total of 3014 operations were performed. Follow-up included 18523 years and was 98% complete. Incidence rates, Kaplan-Meier estimates, modeling of the hazard and multivariate analysis in the hazard domain were used in the analysis. RESULTS Overall survival was 76%, 64%, 51%, 38.5% and 29% at 5, 10, 15, 20 and 25 years, respectively. It was significantly better in aortic than in mitral than in double prosthesis. 290 patients received a single reoperation, 37 a second, six a third and one a fourth reoperation. Two-hundred and fifty-one of these reoperations were exclusively due to malfunction of mechanical prosthesis, nine to malfunction of both mechanic and biologic prostheses. Most frequent reoperative indications was dehiscence (133), pannus (48) and thrombosis (29). The linearized rate of reoperations for pannus was 0.24%/patient per year, for valvular thrombosis 0.15%/patient per year. The shape of the thrombotic hazard was constant (at random) and the relative risk 12 times higher for tricuspid prosthesis, seven times higher for mitral prosthesis. Multivariate analysis controlling for prosthetic position, age, sex and prosthetic size, showed a 67% risk reduction with larger prosthesis (>27 mm), a 69% risk reduction with the Sorin tilting disk prosthesis and an 83% risk reduction with the bileaflet prosthesis. Pannus hazard shows a delayed exponential rise and was two times higher in tricuspid and three times higher in mitral position. Multivariate analysis showed a 50% risk reduction with larger prosthesis, an 11 times higher hazard of old (caged-disk, caged ball) prosthesis and a three times higher hazard of Lillehei-Kaster prosthesis. Reoperation for thrombosis has a 62% perioperative (30 days) survival compared to 92% survival of pannus reoperation. CONCLUSIONS Mechanical valves have a low incidence of reoperation, mostly for prosthetic dehiscence. Pannus development is the next frequent complication increasing with time since implant, therefore in this series it was related to old valvular models and tilting disk prosthesis, with longer follow-up. Acute thrombosis occurs significantly earlier than pannus formation. Despite shorter follow-up we are therefore confident that bileaflet prostheses are less prone to this complication and pannus is a rare early etiologic factor. Thrombosis has very high operative risk as compared to pannus, justifying the present trend to thrombolysate selected cases.

Accuracy of electrocardiographic and echocardiographic indices in predicting life threatening ventricular arrhythmias in patients operated for tetralogy of Fallot

OBJECTIVE To validate the accuracy of the prognostic significance of non-invasive clinical diagnostic indices as predictors of sustained ventricular tachycardia (sVT) or fibrillation (VF) in patients undergoing repair for tetralogy of Fallot. METHODS One way analysis of variance and pairwise comparison of the values with the Bonferroni correction, logistic multivariate analysis, and ordinal logistic analysis were used to study quantitative electrocardiographic and echocardiographic variables in 66 patients who had undergone surgery for tetralogy of Fallot by ventriculotomy at a mean (SD) age of 11.8 (9.5) years. The mean (SD) period of follow up was 16.1 (5.7) years after surgery. RESULTS Four groups of patients were identified by ECG and 24 hour Holter monitoring: 19 (28.7%) without ventricular arrhythmias, 34 (51.5%) with minor ventricular arrhythmias, seven (10.6%) with non-sustained ventricular tachycardia (nsVT), and six (9.0%) with sVT or VF. One way analysis indicated significant differences in QT dispersion (QTd) and end diastolic volume of the right ventricle (EDVRV) among the groups. Univariate logistic analysis showed EDVRV, QTd, and QRS duration to be significantly associated with sVT or VF. Stepwise multivariate analysis and ordinal logistic analysis showed QTd to be preferable to QRS duration as an indicator, because it was unrelated to EDVRV, and was capable of separating different probability curves for nsVT as opposed to sVT or VF. CONCLUSIONS Stratification of patients undergoing corrective surgery for tetralogy of Fallot and at risk of life threatening arrhythmias is possible by simple and inexpensive means, which provide sensitive and specific indices.

The fate of Hancock II porcine valve recipients 25 years after implant

OBJECTIVE The Hancock II (HII) is a second-generation porcine bioprosthesis introduced into clinical use in 1982. This study aimed to evaluate very long-term outcomes for the HII valve in a large patient population. METHODS Between May 1983 and November 1993, 517 consecutive patients (pts) (309 male, mean age: 64+/-9 years) underwent valve replacement (VR) surgery with HII, with 302 (58.4%) in the aortic VR (AVR) and 215 (41.6%) in the mitral VR (MVR) position, respectively. At implant, 106 pts (20.5%) were <60 years of age (G1), while 411 (79.5%) were > or =60 years of age (G2). The 25-year follow-up was complete for all pts at a median of 12 years (range: 0-25). RESULTS Long-term death occurred in 208 AVR and in 165 MVR pts. Survival at 15 and 20 years was 39.5% and 23.3% in AVR pts and 39.0% and 15.8% in MVR pts. At 25 years the survival of MVR pts was 13.7% (four pts at risk). Late freedom from re-operation was 85.5% and 79.3% at 15 and 20 years in the AVR pts and 73.3% and 52.8% in the MVR pts, respectively. In the AVR population, 20-year freedom from re-operation was 52.2% in G1 pts and 86.8% in G2 pts (p<0.0001), while in the MVR population it was 41.4% in G1 pts and 61.9% in G2 pts (p=0.201), respectively. CONCLUSIONS These results confirm the excellent long-term performance of the HII bioprosthesis.

Prosthetic replacement of the tricuspid valve: biological or mechanical?

BACKGROUND Incidence of tricuspid prosthesis replacement was 1.9% of all valvular operations performed between June 6, 1966 and April 18, 1996. Many series report similar figures, but institutional experience is limited and the consensus on treatment modalities is lacking. METHODS One hundred tricuspid operations were performed on 83 patients (46 female). A primary operation was performed in 64 cases, 13 patients had one previous operation, 4 patients had two previous operations, and 2 patients had three previous operations. Seventeen patients required a tricuspid prosthetic valve rereplacement. There were 2 emergent and 17 urgent operations. The New York Heart Association class was IV in 13 patients (mean pulmonary artery pressure, 41 mm Hg), III in 66 patients (mean pressure, 38 mm Hg), and II in 21 patients. The most frequent operation was simultaneous replacement of the mitral and tricuspid valve (41 patients). Seventy biological and 30 mechanical prostheses were used. Total follow-up time was 613 years, mean 7.4 years (median 4.2 years), with a maximum of 27.8 years, and was 92% complete. RESULTS Operative mortality was 24%. Survival was 0.54 (0.48 to 0.59, n = 39) at 5 years, 0.38 (0.32 to 0.44, n = 27) at 10 years, 0.31 (0.25 to 0.36, n = 19) at 15 years, 0.29 (0.23 to 0.34, n = 11) at 20 years, and 0.17 (0.098 to 0.26, n = 3) at 25 years. Early mortality was increased from higher New York Heart Association class (hazard ratio = 2.2), congenital disease (hazard ratio = 6.9), and valvuloplasty failure (hazard ratio = 4.3). The constant risk phase (4%/patient-year) after 2 years was enhanced by older operative age (hazard ratio = 1.4). Prosthetic type had no independent effect. Biological prostheses were at risk for 300 years and had a reoperation incidence of 4.7%/ patient-year (14 events); mechanical prosthesis were at risk for 137 years with a rate of 2.2%/patient-year (3 events) (p = 0.21). Three valve thromboses were observed in old-design mechanical prosthesis. Bioprosthetic degeneration showed a steeper rate after 7 years. CONCLUSIONS This study does not show a clear superiority of biological versus mechanical prostheses. In the long run survival with mechanical prostheses could be superior, given the high rate of bioprosthetic degeneration after 7 years.

Clinical significance of high-frequency, low-amplitude electrocardiographic signals and QT dispersion in patients operated on for tetralogy of Fallot.

Abstract In conclusion, we found that in patients operated on for tetralogy of Fallot, signal-averaged electrocardiography is not useful for identifying patients at risk for severe ventricular arrhythmia, but the measurement of QT dispersion might be an appropriate noninvasive marker of electrical instability.