Two paleopathological cases suggestive of paralabral cysts of the shoulder.

OBJECTIVE: To undertake differential diagnosis of scapular bone defects found in two medieval skeletons buried in different necropoles of Friuli Venezia Giulia (Italy) and to evaluate the clinical significance of paralabral cysts in the context of shoulder pathology. MATERIALS: Individual JoT36 is an adult male exhumed from a necropolis belonging to a rural agricultural settlement dated to the 10th to 11th century A.D. Individual CIVT58 is an adult male from a Langobard necropolis dated to 630-670 A.D. METHODS: Macroscopic examination of the skeletons was performed using standard osteological methods and review of pertinent clinical literature to assist differential diagnosis. RESULTS: Between the glenoid cavity and the spinoglenoid notch of the right scapula of JoT36 there is a multilocular circular defect adjacent to the glenoid rim. On the neck of the left scapula of CIVT58, immediately above the spinoglenoid notch, there is a unilocular circular depression. In both cases, the cortical bone appears smooth without any evidence of erosion or sclerosis. CONCLUSIONS: Skeletal findings and historical/archaeological contexts of both cases are compatible with the diagnosis of paralabral cysts. SIGNIFICANCE: Paralabral cysts are relatively frequently observed in clinical settings but very few examples have been documented in paleopathological literature. This study seeks to improve recognition and interpretation of this pathology in historical/archaeological contexts. LIMITATIONS: Findings from a case report can neither generate epidemiological information nor be generalized. SUGGESTIONS FOR FURTHER RESEARCH: Identification of new cases may add valuable information about lifestyles and related shoulder pathologies in ancient times.

A mandibular bone defect of uncertain significance: report of a paleopathological case.

Anatomical variations of the mandibular canal as well as the presence of accessory canals and foramina are common findings in the human mandible. Here, we present a previously unreported type of anatomical variation, consisting of a large full-thickness bone defect of the right mandibular ramus, observed in a young male unearthed from a mediaeval cemetery located in North-Eastern Italy. The defect was located very close to, yet not directly connected with, the mandibular canal. Awareness of the existence of deviations from the anatomical norm such as that we describe here is strategic to avoid diagnostic misinterpretations, minimise technical hitches, and prevent clinical complications during invasive procedures in the region of the mandible.

Long-term evolution and prognostic stratification of biopsy-proven active myocarditis.

BACKGROUND: Active myocarditis is characterized by large heterogeneity of clinical presentation and evolution. This study describes the characteristics and the long-term evolution of a large sample of patients with biopsy-proven active myocarditis, looking for accessible and valid early predictors of long-term prognosis. METHODS AND RESULTS: From 1981 to 2009, 82 patients with biopsy-proven active myocarditis were consecutively enrolled and followed-up for 147±107 months. All patients underwent clinical and echocardiographic evaluation at baseline and at 6 months. At this time, improvement/normality of left ventricular ejection fraction (LVEF), defined as a LVEF increase > 20 percentage points or presence of LVEF≥50%, was assessed. At baseline, left ventricular dysfunction (LVEF<50%) and left atrium enlargement were independently associated with long-term heart transplantation-free survival, regardless of the clinical pattern of disease onset. At 6 months, improvement/normality of LVEF was observed in 53% of patients. Persistence of New York Heart Association III to IV classes, left atrium enlargement, and improvement/normality of LVEF at 6 months emerged as independent predictors of long-term outcome. Notably, the short-term reevaluation showed a significant incremental prognostic value in comparison with the baseline evaluation (baseline model versus 6 months model: area under the curve 0.79 versus 0.90, P=0.03). CONCLUSIONS: Baseline left ventricular function is a marker for prognosis regardless of the clinical pattern of disease onset, and its reassessment at 6 months appears useful for assessing longer-term outcome.

A keyhole-shaped sternal defect in an ancient human skeleton.

We observed a sternal foramen contiguous with a small sternal cleft in a human skeleton coming from North-Eastern Italy and dating back to between the sixteenth and seventeenth century AD. Both of these types of anomalies result from a defective midline fusion of the developing sternum. Sternal foramen is a relatively common bony defect that usually comes to light as an incidental finding. Sternal cleft is a rarer morphological anomaly that can have a wide spectrum of clinical manifestations and outcomes, depending on the extent of the bony defect as well as on the presence and severity of other abnormalities. The coexistence of a sternal foramen and a sternal cleft has very rarely been described in the literature. We report here one such unusual association and discuss its potential practical implications. In most cases, sternal foramina and small sternal clefts are clinically uneventful; yet, lack of awareness about the existence of these subtle anatomical variations can sometimes lead to misinterpretation of radiological and pathological findings or make sternal biopsy and acupuncture unsafe.

Bilateral arcuate foramen associated with partial defect of the posterior arch of the atlas in a medieval skeleton: case report and review of the literature. Looking backward to go forward.

PURPOSE: We observed a complex atlas (C1) dysmorphism in a human medieval skeleton dug up from the sixth to the seventh century necropolis located in the north-eastern Italy. We analyzed such a dysmorphism in the light of pertinent literature and discussed the functional and clinical implications related to this type of C1 structural malformation. METHODS: Macroscopical and CT-SCAN examinations of the atlas were carried out. RESULTS: Bone findings consisted of partial aplasia of the posterior arch of the C1 accompanied by a bilateral arcuate foramen. In addition, the spinous processes of C7 and T1 were found to be bifid. CONCLUSIONS: Although such abnormalities are supposed to be clinically inconspicuous, yet they may become challenging or even dangerous in the context of trauma. They may even complicate specific diagnostic or surgical procedures. In addition, they may cause a great number of symptoms, ranging from headache and neck pain to loss of postural muscle tone and consciousness, due to the close and complex relationship of bone structures with nerves, blood vessels, muscles, and ligaments. As a result, radiologists, clinicians, surgeons, and chiropractors should consider in their clinical reasoning the possibility that atlas dysmorphisms may occur.

Deleterious impact of mild anemia on survival of young adult patients (age 45 ± 14 years) with idiopathic dilated cardiomyopathy: data from the Trieste Cardiomyopathies Registry.

OBJECTIVE: The study objective was to evaluate the impact of anemia on a large population of young patients with idiopathic dilated cardiomyopathy (DCM) who were receiving optimal medical treatment. METHODS: The data of 491 patients with DCM who were enlisted in the Trieste Heart Muscle Disease Registry were analyzed. Anemia was defined as hemoglobin less than 13 g/dL for male patients and less than 12 g/dL for female patients. RESULTS: At baseline, 13% of our patients were anemic. During the follow-up of 134 ± 56 months, 144 patients died or underwent heart transplantation: 36.5% anemic patients and 28% non-anemic patients (P = .05). Anemia present at baseline was an independent predictor of outcome (hazard ratio = 1.85, P = .014). Serial hemoglobin determinations during the entire follow-up were available in 122 of 428 patients without anemia at baseline. The impact of new-onset anemia was analyzed in this cohort of patients. Forty-seven patients (39%) developed anemia during follow-up. The new onset of anemia was an independent predictor of poor outcome (hazard ratio = 2.85, P = .02). CONCLUSION: The presence or development of mild anemia in young patients with optimally treated idiopathic DCM is frequent and associated with a worse outcome.

Impact of atrial fibrillation on outcome of patients with idiopathic dilated cardiomyopathy: data from the Heart Muscle Disease Registry of Trieste.

OBJECTIVE: There is a paucity and inconsistency of data regarding the natural history of patients affected by idiopathic dilated cardiomyopathy (IDCM) and atrial fibrillation (AF). We examined the prognostic implications of AF in a subset of patients with IDCM. METHODS: We analyzed the data of 539 patients with IDCM enrolled in the Heart Muscle Disease Registry of Trieste. RESULTS: At baseline, 52 (9.6%) of 539 patients had AF. There was no difference in survival of patients with either AF or sinus rhythm at enrollment (P = .28). During long-term follow-up (90 ± 58 months), AF was detected on ECG/ECG-Holter monitoring in 28 (5.7%) of 487 patients in sinus rhythm at baseline. Predictors of new onset of AF at multivariate analysis were a more dilated left atrium (OR 1.35, 95% CI 1.06-1.72; P = .01) and a lower left ventricle ejection fraction (for 10% decrease, OR 2.41, 95% CI 1.24-4.69, P = .016). Patients developing AF had higher mortality/heart transplantation rate compared to patients who maintained sinus rhythm during follow-up (P < .001). At multivariate analysis, new onset AF (HR 3.67, 95% CI 2.07-6.5; P < .001) in the first three years after diagnosis, but not baseline AF, was found to be independently associated with a worse outcome. CONCLUSIONS: Atrial fibrillation is relatively frequent in patients with IDCM. The early development of AF during follow-up, but not its presence at baseline, is associated with poor survival.

[If heart failure or cardiac arrest complicate pregnancy and delivery]. / Quando lo scompenso o l'arresto cardiaco complicano la gravidanza ed il parto.

Physiological adaptation to pregnancy exposes mother's cardiovascular system to relevant hemodynamic overload. These changes and other specific conditions of pregnancy, such as amniotic embolism, can point out unrecognized preexisting heart disease or, in the presence of some cofactors, be burdensome even for healthy hearts. Thus, tragic cases of heart failure or cardiac arrest may occur, whose management requires several considerations with respect of trying to save two lives at the same time, the need for drugs potentially harmful to the fetus, and assessment of emergent cesarean section.

Relative survival in dilated cardiomyopathy: a stratification study of long-term outcome to evaluate life insurance cover.

OBJECTIVES: The aim of this study was to compare mortality of dilated cardiomyopathy (DCM) patients with the mortality in the background Italian population, taking into account demographic characteristics and clinical stratification of long-term outcome, ie, "reverse remodelling" within the first 2 years of follow-up. BACKGROUND: DCM is a myocardial disease, characterized by left and/or right ventricular dilation and dysfunction and poor outcome. Evidence-based treatment with ACE inhibitors, beta-blockers and, in the last decade, implantable cardioverter defibrillators have been demonstrated to improve significantly heart failure symptoms and prognosis. At present, DCM patients are unlikely to be accepted for life insurance. METHODS: A cohort of 577 DCM patients consecutively enrolled from 1988 to 2004 in the Heart Muscle Disease Registry of Trieste, Italy, was matched by sex, age and registry data entry with the mortality data of the Italian population. Relative survival has been estimated by means of Kaplan-Meier technique, and mortality ratios (MR) with corresponding 95% confidence intervals have been computed. RESULTS: DCM patients who showed a significant reverse remodelling within the first 2 years of treatment showed comparable survival with respect to the control population, and therefore could be taken into consideration for life insurance coverage, at least for a short or medium-term of years. CONCLUSIONS: The data illustrate that survival probability strongly depend on the individual treatment and evolution of the disease and could be easily measured within the first 2 years of follow-up. If this information is collected at the time of evaluation of an applicant for life cover, the insurance company could possibly improve its risk stratification.

Natural history of dilated cardiomyopathy: from asymptomatic left ventricular dysfunction to heart failure--a subgroup analysis from the Trieste Cardiomyopathy Registry.

BACKGROUND: Few data are available in the literature regarding the characteristics and prognosis of asymptomatic patients with idiopathic dilated cardiomyopathy (DCM). AIM: To determine the frequency with which patients affected by DCM are diagnosed in the asymptomatic state as well as to evaluate the natural history of such patients and the factors influencing their outcome. Moreover, we sought to compare the outcome of asymptomatic patients with that of patients with signs of overt heart failure at the time of first evaluation. METHODS AND RESULTS: We analyzed the data of 747 patients with DCM enlisted in the Heart Muscle Disease Registry of Trieste from 1978 to 2007. We divided our population into four groups; group 1 comprised 118 asymptomatic [New York Heart Association (NYHA) I] patients without a history of congestive symptoms (16%), group 2 comprised 102 asymptomatic (NYHA I) patients (14%) with a positive anamnesis for heart failure stabilized in medical therapy, group 3 comprised 327 patients (44%) with signs of mild heart failure (NYHA II) and group 4 comprised 200 patients (26%) in NYHA III-IV. During the follow-up of 112+/-63 months, 46 (21%) of 220 asymptomatic patients with DCM died or underwent heart transplantation. By Cox proportional model, left ventricular ejection fraction of 30% or less was a unique independent predictor either for death/heart transplantation (hazard ratio 3.15, 95% confidence interval 1.5-6.7, P=0.003) or for sudden death/major ventricular arrhythmias (hazard ratio 3.9, 95% confidence interval 1.7-9.3, P=0.002). Patients from group 1 had a trend for a better outcome with respect to those from group 2 (P=0.06). In comparison with the asymptomatic patients, those with signs of overt heart failure at baseline had a worse prognosis. CONCLUSION: The proportion of asymptomatic patients with DCM at the moment of first evaluation at our center is significant (30%). Among them, those without a previous history of heart failure had a less advanced disease and a trend for a better long-term outcome on optimal medical treatment. Therefore, early diagnosis may offer better long-term quality of life and even better survival. Further studies on larger populations are indicated.

Right ventricular cardiomyocyte apoptosis in patients with acute myocardial infarction of the left ventricular wall.

Cardiac remodeling after acute myocardial infarction (AMI) is characterized by molecular and cellular mechanisms involving both the left (LV) and right ventricular (RV) walls. Cardiomyoycte apoptosis in the peri-infarct and remote LV myocardium has a central role in cardiac remodeling. Whether apoptosis also occurs in the right ventricle of patients with ischemic heart disease has not been investigated. The aim of the present study was to investigate the presence of cardiomyocyte apoptosis in the right ventricle in patients with AMI. We assessed the number of apoptotic cardiomyocytes using multiple samplings in the LV and RV walls of 12 patients selected at autopsy who died 4 to 42 days after AMI. Five patients without cardiac disease were also selected at autopsy as controls. Apoptotic rates were calculated from the number of cardiomyocytes showing double positive staining for in situ end-labeling of DNA fragmentation (TUNEL) and for activated caspase-3. Potentially false-positive results (DNA synthesis and RNA splicing) were excluded from cell counts. The apoptotic rate in the right ventricle in patients with AMI was significantly higher than in control hearts (median 0.8%, interquartile range 0.3 to 1.0 vs median 0.01%, interquartile range 0.01 to 0.03, p <0.001). RV apoptosis significantly correlated with such parameters of global adverse remodeling as cardiac diameter to LV free wall thickness (R = +0.57, p = 0.050). RV apoptosis was significantly higher in five cases (42%) with infarct involving the ventricular septum and an adjacent small area of the RV walls (median 1.0%, interquartile range 0.8 to 2.2 vs median 0.5%, interquartile range 0.2 to 1.0, p = 0.048, p <0.001 vs controls). The association between apoptotic rate in the right ventricle and cardiac remodeling was apparent even after exclusion of cases with RV AMI involvement (R = +0.82, p = 0.023 for diameter to LV wall thickness ratio and R = -0.91, p = 0.002 for RV free wall thickness). In conclusion, patients with cardiac remodeling after AMI had a significant increase in RV apoptosis even when ischemic involvement of the RV wall was not apparent.

Are nonsustained ventricular tachycardias predictive of major arrhythmias in patients with dilated cardiomyopathy on optimal medical treatment?

BACKGROUND: To evaluate the role of nonsustained ventricular tachycardias (NSVT) for the prediction of major ventricular arrhythmias (MVA) in patients with idiopathic dilated cardiomyopathy (DCM) after optimization of medical treatment. METHODS AND RESULTS: Three hundred nineteen consecutive DCM patients were evaluated after adequate stabilization on optimal angiotensin-converting enzyme (ACE) inhibitor (88%) and beta-blocker (82%) therapy. Frequency, length, and rate of NSVT at 24-hour Holter monitoring were analyzed to assess their values in predicting MVA (unexpected sudden death, SVT, ventricular fibrillation, and appropriate implantable cardioverter defibrillator interventions). During follow-up (median 96 months, 1(st)-3(rd) interquartile range 52-130), MVA incidence was low, and not statistically different between patients with and without NSVT (3 and 2 per 100 patient-years, respectively, P = nonsignificant [NS] at log-rank analysis). At multivariable analysis, the number of NSVT was predictive of MVA only if left ventricular ejection fraction (LVEF) was > 0.35 (two NSVT/day vs no NSVT/day: hazard ratio [HR] 5.3, 95% confidence interval [CI] 1.59-17.85 in LVEF > 0.35 vs HR 0.93, 95% CI 0.3-2.81 in LVEF < or = 0.35). Consequently, in patients with LVEF < or = 0.35, MVA incidence rates were similar regardless of NSVT (3.6 and 4.1 patient-years, respectively, in those with and without NSVT, P = NS), while in patients with LVEF > 0.35, MVA incidence (3.1 per 100 patient-years vs 0.9 per 100 patient-years, P = 0.003) was significantly higher when NSVT were present. CONCLUSIONS: After medical stabilization, NSVT did not increase the risk of MVA in patients with DCM and LVEF < or = 0.35. Conversely, the number and length of NSVT runs were significantly related to the occurrence of MVA in the patients with LVEF > 0.35.

Unusual case of occipital vertebra in a medieval skeleton.

The craniovertebral junction (CVJ) is a transitional region of the spine that exhibits extensive structural variability. Developmental defects include a vast array of anatomical anomalies that result from remnants of the proatlas and are grouped under the term 'occipital vertebra'. The purpose of the present paper is to describe the case of a medieval skeleton, which was found to display a previously unreported manifestation of occipital vertebra. It consisted of two large basilar processes that articulated with the anterior arch of the atlas. In addition, the left process exhibited a supplementary contact zone with the dens of the axis. These structural defects were associated with an accessory canal situated posterior to the right hypoglossal canal.

[Triple/quadruple therapy in heart failure: integrating scientific evidence with clinical reasoning]. / La tripla/quadrupla terapia antineurormonale nello scompenso cardiaco tra dubbi, evidenze scientifiche e buon senso clinico.

Anti-neurohormonal pharmacological agents successfully tested in randomized controlled trials over the last two decades - firstly angiotensin-converting enzyme inhibitors (ACE-I), then beta-blockers (BB) and more recently aldosterone receptor-antagonists (ARA) and angiotensin II receptor blockers (ARB) - have significantly contributed to increase the chance of favorable outcomes in patients with chronic heart failure. An ACE-I and a BB, usually combined with diuretics and often with digoxin, continue to represent the cornerstones for the treatment of heart failure; moreover, most patients who are taking these drugs are now expected to receive as add-on therapies also an ARA and/or an ARB. However, as the number of available drugs increases coupled with the hope of greater clinical benefits, these more complicated pharmacological options are destined to generate even more controversy. Now, much debate is over to which triple (ACE-I + BB + ARA or ARB) and quadruple (ACE-I + BB + ARA + ARB) therapies may be offered. Current guidelines do not fully address the aim of providing straightforward guidance about what should be the third drug of the triple therapy and as to whether or not quadruple therapy may have any role in the present-day heart failure management. Adapting any pharmacological strategy--based upon both scientific evidence and clinical reasoning--to the specific profile of the individual patient can be helpful to circumvent uncertainties and errors in daily practice of medicine and make the best use of currently available drugs.

Left ventricular diastolic filling pattern at Doppler echocardiography and apoptotic rate in fatal acute myocardial infarction.

Heart failure is a complex syndrome characterized by impaired emptying and/or impaired filling of the heart chambers. The use of parameters of diastolic function has provided novel tools for risk stratification and management of patients with heart failure. This study evaluated the potential correlation between apoptosis at time of death and left ventricular (LV) diastolic function after acute myocardial infarction. We selected, at routine postmortem examination, 14 subjects who died 10 to 62 days after an acute myocardial infarction and had an available echocardiographic report from the most recent hospital admission. The apoptotic rate was calculated at the region bordering the infarct, using co-localization of in situ end-labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3. Transthoracic echocardiographic studies were retrospectively reevaluated and pulse-wave Doppler spectra of mitral inflow were analyzed. LV diastolic function was assessed by measuring the ratio of E peak velocity to A peak velocity and E-wave deceleration time; a ratio of E peak velocity to A peak velocity >or=2 and deceleration time <115 ms were considered a restrictive filling pattern. A restrictive pattern was found in 4 cases (29%). All subjects with a restrictive pattern were symptomatic for New York Heart Association class IV heart failure (100% vs 20%, p = 0.015) and had larger transverse heart diameters at pathology (p = 0.014). The apoptotic rate in the peri-infarct region was significantly higher in patients with a restrictive versus nonrestrictive diastolic pattern (13%, 10 to 14, vs 3%, 1 to 6, p = 0.014). At multivariable analysis that included the restrictive pattern, class IV heart failure, and cardiac diameters, the restrictive pattern remained an independent predictor of increased apoptosis (p = 0.030). In conclusion, patients with severe postinfarction LV diastolic dysfunction had significantly higher rates of cardiomyocyte loss by apoptosis, which may partly explain their unfavorable outcome.

Prognostic role of non-sustained ventricular tachycardia in a large cohort of patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The identification of patients with idiopathic dilated cardiomyopathy (IDC) at higher risk of sudden death (SD) is still an unsolved issue, and the role of non-sustained ventricular tachycardia (NSVT) uncertain. METHODS: The effect of NSVT on total mortality, SD and life-threatening arrhythmias was evaluated in 554 patients with IDC on optimal medical treatment and at long-term follow-up (81 +/- 58 months). RESULTS: At diagnosis, 240 patients (43%) had NSVT at Holter monitoring and 314 (57%) did not. During follow-up, 189 patients (5/100 patients-year) died or underwent heart transplantation; SD occurred in 53 patients (1.4/100 patients-year); SD + non-fatal ventricular arrhythmias occurred in 75 patients (2/100 patients-year). Patients with and without NSVT at diagnosis had the same 5-year transplant-free survival rate (76 vs 76%, p = NS) and a similar incidence of SD (10 vs 7%, p = NS). The length and rate of NSVT did not show any significant relationship with the outcome. Only heart failure symptoms (NYHA class III-IV) (hazard ratio [HR] 1.9, p = 0.015) and severe left ventricular impairment (left ventricular ejection fraction < or = 0.30 and left ventricular end-diastolic diameter > or = 70 mm) (HR 2.7, p < 0.0001) were independently associated with higher SD risk. At multivariate analysis the presence of frequent NSVT episodes (> or = 3 runs/day) was associated with an increased risk of total mortality (HR 1.68, p = 0.041) and of major ventricular arrhythmias (HR 2.11, p = 0.037), but only in the subgroup of patients with severe left ventricular impairment. CONCLUSIONS: Patients with advanced heart failure symptoms, severe left ventricular dysfunction and dilation had a higher risk of SD independently of NSVT. The finding of more frequent NSVT was associated with an increased risk of all-cause mortality and of major ventricular arrhythmias in patients with severe left ventricular impairment.

Idiopathic dilated cardiomyopathy: prognostic significance of electrocardiographic and electrophysiologic findings in the nineties.

BACKGROUND: With the exception of a few cases such as aborted sudden cardiac death, sustained ventricular tachycardia, and syncope of unexplained origin, there is no consensus on the clinical findings identifying patients with idiopathic dilated cardiomyopathy with an increased risk of sudden cardiac death or malignant ventricular arrhythmias. METHODS: To verify whether electrocardiographic and arrhythmologic features could be useful for prognostic stratification, 78 consecutive patients with an invasive diagnosis of idiopathic dilated cardiomyopathy, but without symptomatic ventricular arrhythmias, were enrolled in a prospective study. Signal-averaged ECG, 24 to 48 hour ECG monitoring and electrophysiologic study were performed at the time of diagnosis to identify arrhythmogenic predictors of outcome. Transplant-free and arrhythmic event-free survival was evaluated on the basis of initial parameters. RESULTS: During a mean follow-up of 85 months, 9 patients died (6 of sudden cardiac death and 3 of congestive heart failure), 10 patients underwent cardiac transplantation for refractory heart failure, and 3 presented with sustained ventricular tachycardia. The independent predictors for death and cardiac transplantation were an HV interval > 55 ms and the combination of frequent repetitive ventricular ectopics with a poor left ventricular function. A strong index of arrhythmic events proved to be the association of a prolonged HV interval with a wide (> 110 ms) QRS complex (odds ratio 4.53, 95% confidence interval 1.57-13.04, p < 0.005). CONCLUSIONS: An accurate measurement of the HV interval and QRS duration at baseline evaluation may add prognostic information in patients with idiopathic dilated cardiomyopathy. In our experience, abnormal values of both parameters identified a group of patients with a very high risk of late occurring arrhythmic events.

[The natural history of dilated cardiomyopathy: a review of the Heart Muscle Disease Registry of Trieste]. / Come è cambiata la storia naturale della cardiomiopatia dilatativa. Una revisione del Registro delle Malattie del Miocardio di Trieste.

Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers. However, a strong heterogeneity of prognosis was observed among patients both in familial and sporadic cases. Early diagnosis and treatment allowed to recognize two distinct subgroups, one with a rapidly progressive downhill course, high mortality and urgent indication to heart transplantation, another with a more favorable outcome. Long-term optimized treatment with ACE-inhibitors (in 90% of cases) and beta-blockers (in 87% of cases) was associated with a remarkable clinical improvement in 50% of patients and apparent "healing" in 16% of cases. A systematic and accurate echocardiographic follow-up showed in these cases a significant improvement of the left ventricular ejection fraction (LVEF) with "reverse remodeling", frequently associated with a decrease of severity of functional mitral regurgitation and regression of the restrictive filling pattern. The response to optimal treatment showed a strong relation to long-term outcome. The 8-year transplant-free survival, starting from the evaluation at 2 years, was 31% in patients with persistent NYHA class III-IV, 64% in NYHA class I-II and LVEF < or = 40%, 83% in NYHA class I-II and LVEF > 40% and 94% in patients with apparent "healing" (p < 0.0001). Long-term follow-up showed a significant clinical progression of the disease in 33% of cases, independently of the initial clinical response to treatment. Predictive factors of a favorable response to beta-blocker treatment associated with ACE-inhibitors were a history of mild hypertension, an early diagnosis and treatment and the presence of sinus tachycardia. The risk of sudden death was increased particularly in patients with long-term persistent or progressive left ventricular dilation and dysfunction. A rigorous pharmacological approach (optimization of beta-blockers, withdrawal or decrease of dosage of digitalis), and selective non-pharmacological strategy (automated implantable cardioverter-defibrillators for primary prevention in high-risk patients) are potentially effective to decrease the incidence of sudden death during long-term follow-up. In conclusion, the Heart Muscle Disease Registry of Trieste gave us in the last 25 years new insights into the natural history of DCM, underlying the importance of a rigorous and systematic approach both at clinical presentation and during long-term follow-up on optimized medical treatment.

[How the natural history of dilated cardiomyopathy has changed. Review of the Registry of Myocardial Diseases of Trieste]. / Come è cambiata la storia naturale della cardiomiopatia dilatativa. Una revisione del Registro delle Malattie del Miocardio di Trieste.

Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers. However, a strong heterogeneity of prognosis was observed among patients both in familial and sporadic cases. Early diagnosis and treatment allowed to recognize two distinct subgroups, one with a rapidly progressive downhill course, high mortality and urgent indication to heart transplantation, another with a more favorable outcome. Long-term optimized treatment with ACE-inhibitors (in 90% of cases) and beta-blockers (in 87% of cases) was associated with a remarkable clinical improvement in 50% of patients and apparent "healing" in 16% of cases. A systematic and accurate echocardiographic follow-up showed in these cases a significant improvement of the left ventricular ejection fraction (LVEF) with "reverse remodeling", frequently associated with a decrease of severity of functional mitral regurgitation and regression of the restrictive filling pattern. The response to optimal treatment showed a strong relation to long-term outcome. The 8-year transplant-free survival, starting from the evaluation at 2 years, was 31% in patients with persistent NYHA class III-IV, 64% in NYHA class I-II and LVEF < or = 40%, 83% in NYHA class I-II and LVEF > 40% and 94% in patients with apparent "healing" (p < 0.0001). Long-term follow-up showed a significant clinical progression of the disease in 33% of cases, independently of the initial clinical response to treatment. Predictive factors of a favorable response to beta-blocker treatment associated with ACE-inhibitors were a history of mild hypertension, an early diagnosis and treatment and the presence of sinus tachycardia. The risk of sudden death was increased particularly in patients with long-term persistent or progressive left ventricular dilation and dysfunction. A rigorous pharmacological approach (optimization of beta-blockers, withdrawal or decrease of dosage of digitalis), and selective non-pharmacological strategy (automated implantable cardioverter-defibrillators for primary prevention in high-risk patients) are potentially effective to decrease the incidence of sudden death during long-term follow-up. In conclusion, the Heart Muscle Disease Registry of Trieste gave us in the last 25 years new insights into the natural history of DCM, underlying the importance of a rigorous and systematic approach both at clinical presentation and during long-term follow-up on optimized medical treatment.