Cardiomyopathy: a necessary revision of the WHO classification

The classification of myocardial disease proposed by the WHO/ISFC task force in 1980 distinguishes specific heart muscle diseases from myocardial diseases of unknown origin, termed cardiomyopathies, and differentiated into the dilated, hypertrophic and restrictive forms. This last group includes endomyocardiofibrosis and fibroblastic parietal endocarditis. In more recent years, two new forms of heart muscle disease have been recognized: so-called "primary" restrictive cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Primary restrictive cardiomyopathy is characterized anatomically by normally sized, non-hypertrophic ventricles with dilated atria, and functionally by impaired diastolic compliance due to myocardial stiffness. The clinical picture is that of chronic congestive heart failure; histology shows interstitial fibrosis and myocardial disarray, but not hypereosinophilia. In arrhythmogenic right ventricular cardiomyopathy, the myocardium of the right ventricular free wall is substituted by fibrous and/or adipose tissue, which results in regional dynamic alterations and ominous ventricular arrhythmias. The left ventricle is usually spared. Both forms should be classified as heart muscle diseases of unknown origin, and kept clearly distinct from the other cardiomyopathies listed in the WHO classification.     

Cardiovascular and renal alterations on the nitric oxide pathway in spontaneous hypertension and ageing

We have assessed the NO system in the cardiovascular and renal systems of young, adult and old normotensive (WKY) and hypertensive rats (SHR). The NO pathway was assessed analytically, by measuring the concentration of nitrate in plasma as well as the activity of NO synthases in the left ventricle and kidney; and functionally, by measuring the isometric forces generated upon addition of the NO blocker, L-NAME, to aortic segments. All these procedures consistently revealed that the NO pathway is upregulated in hypertension or senescence. In addition, we have performed immunohistochemical studies of NO synthases in the kidney of adult animals (WKY and SHR). NO synthases are expressed throughout the kidney in both rat strains. Immunoreactivity of neuronal NOS was higher in the tubular cells of the renal medulla of the SHR. Staining with the inducible and endothelial NOS antibodies was similar in normo- and hypertension. In summary, hypertension and ageing upregulate the NO pathway in structures involved in the regulation of blood pressure (heart, vessels and kidney).     

Hemodynamic changes with enalapril in pulmonary arterial hypertension secondary to congenital heart disease

Enalapril was used to treat five patients with pulmonary arterial hypertension secondary to congenital cardiopathy, three with ventricular septal defect, one with arterial septal defect, and one with patent ductus arteriosus. The dose of enalapril was 20 mg/day. All patients underwent pretreatment and posttreatment cardiac catheterization. It was concluded that enalapril may be a useful drug in the treatment of pulmonary arterial hypertension secondary to congenital cardiopathy.     

Follow-up colonoscopy in patients with colorectal adenomatous polyps

Forty-four asymptomatic patients with adenomatous colorectal polyps were followed by repeated colonoscopies and subsequent removal of new polyps. The median follow-up time was 34 months (range, 4 to 131 months). Twenty-six patients (59 percent) developed new adenomatous polyps. Therecurrence rate was 69 percent in patients with multiple polyps compared with 54 percent in patients with a single polyp. The location of new polyps was in the same colonic segment in 81 percent of the patients, but not at the same site in the colon where a previous polyp had been removed. The histopathology and size of new polyps compared with the initial polyps showed a significant improvement in histopathology toward more benign polyps (P<0.02) and smaller polyps (P<0.001). In patients who initially had single adenomatous polyps, new polyp(s) were diagnosed after a mean time of 23 months compared initially. Patients with atypia in initial polyp(s) developed new polyp(s) after a mean time of 11 months compared with 23 months in patients without atypia. The mean time from a colon with no polyps to the diagnosis of a new adenomatous polyp less than 5 mm in size was 11.5 months, which was a statistically significant shorter time than the 19.4 months observed for the development of polyps 5 mm or larger.     

Signal-averaged electrocardiographic parameter progression as a marker of increased electrical instability in two cases with an overt form of arrhythmogenic right ventricular cardiomyopathy

In arrhythmogenic right ventricular cardiomyopathy (ARVC) the fibrofatty substitution of the RV myocardium constitutes the substrate for reentrant circuits, leading to the onset of ventricular arrhythmias. This pathological process also accounts for "delayed ventricular potentials" that could be recorded as late potentials using the signal-averaged ECG technique (SAECG). This study examined two patients affected by overt forms of ARVC who showed a worsening of the electrical instability associated with a fast progression of SAECG parameters, while all the other clinical findings remained unchanged. This suggests a possible role of SAECG parameter progression as a marker of increased electrical instability.     

Long-Term Oxygen Therapy in COPD Patients Who Do Not Meet the Actual Recommendations

Chronic respiratory failure due to chronic obstructive pulmonary disease (COPD) is an increasing problem worldwide. Many patients with severe COPD develop hypoxemic respiratory failure during the natural progression of disease. Long-term oxygen therapy (LTOT) is a well-established supportive treatment for COPD and has been shown to improve survival in patients who develop chronic hypoxemic respiratory failure. The degree of hypoxemia is severe when partial pressure of oxygen in arterial blood (PaO₂) is ≤55 mmHg and moderate if PaO₂ is between 56 and 69 mmHg. Although current guidelines consider LTOT only in patients with severe resting hypoxemia, many COPD patients with moderate to severe disease experience moderate hypoxemia at rest or during special circumstances, such as while sleeping or exercising. The efficacy of LTOT in these patients who do not meet the actual recommendations is still a matter of debate, and extensive research is still ongoing to understand the possible benefits of LTOT for survival and/or functional outcomes such as the sensation of dyspnea, exacerbation frequency, hospitalizations, exercise capacity, and quality of life. Despite its frequent use, the administration of “palliative” oxygen does not seem to improve dyspnea except for delivery with high-flow humidified oxygen. This narrative review will focus on current evidence for the effects of LTOT in the presence of moderate hypoxemia at rest, during sleep, or during exercise in COPD.     

Crystal structure of the synergistic antibiotic pair, lankamycin and lankacidin, in complex with the large ribosomal subunit

The structures of the large ribosomal subunit of Deinococcus radiodurans (D50S) in complex with the antibiotic lankamycin (3.2 Å) and a double antibiotic complex of lankamycin and lankacidin C (3.45 Å) have been determined, in continuation of previous crystallographic studies on lankacidin-D50S complex. These two drugs have been previously reported to inhibit ribosomal function with mild synergistic effect. Lankamycin, a member of the macrolide family, binds in a similar manner to erythromycin. However, when in complex with lankacidin, lankamycin is located so that it can form interactions with lankacidin in the adjacent ribosomal binding site. When compared to the well-documented synergistic antibiotics, Streptogramins A and B, the pair of lankacidin and lankamycin bind in similar sites, the peptidyl transferase center and nascent peptide exit tunnel, respectively. Herein, we discuss the structural basis for antibiotic synergism and highlight the key factors involved in ribosomal inhibition.     

Left ventricular mural thrombus in acute anterior myocardial infarct

Fifty-six consecutive patients with acute anterior infarction were studied by two-dimensional echocardiography to determine the incidence and complications of left-ventricular thrombosis. Mean follow-up period was 4.4 months. Left-ventricular thrombus was demonstrated in 14 patients (25%) between 25 and 54 days after infarction (group A), in 42 patients (group B) it was not demonstrated. Apical and septal dyskinesis, and Forrester's hemodynamic subset-III were significantly (P less than 0.02) associated with thrombus development. Ten patients of group A received heparin (6.6 days mean); the remaining four patients received aspirin and dipyridamole. Thrombi formation were not significantly prevented with both treatments (chi 2 = 0.635). During follow-up period, thrombus persisted in 6 patients of group A, all of them with apical and septal dyskinesis. Three patients had a cerebrovascular accident (5.3%), one of them of group A; no heparin anticoagulation was administered in two. We conclude that apical and septal dyskinesis during acute anterior infarction is generally associated with mural thrombi development. Due to the embolic risk therapeutic anticoagulation must be considered in these patients.     

Spin-echo nuclear magnetic resonance for tissue characterisation in arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disorder characterised clinically by ventricular arrhythmias that can cause cardiac arrest and morphologically by fatty or fibro-fatty myocardial atrophy of the right ventricle. In vivo tissue characterisation without endomyocardial biopsy would be useful. The aim of this study was to investigate the diagnostic accuracy of spin-echo nuclear magnetic resonance (NMR) for tissue characterisation in ARVC. PATIENTS AND METHODS: Twenty three subjects (15 men and eight women, aged 18-49, mean 34) were studied with spin-echo T1-weighted NMR and multislice scan. Fifteen had a clinical diagnosis of ARVC and eight were controls (age and sex matched subjects). Data were independently evaluated by two expert observers. RESULTS: In the control group NMR was always negative (100% specificity). Ten of the 15 patients with ARVC had an abnormal NMR result (67% sensitivity), with areas that had a signal intensity close to that of pericardial or subcutaneous fat. In the remaining five cases the NMR signal was inadequate. Nine patients underwent both NMR and endomyocardial biopsy; biopsy was positive in eight (89%) and NMR was positive in five (56%). CONCLUSIONS: NMR is a useful non-invasive diagnostic tool in the evaluation of fatty replacement in ARVC. The technique can be used with other procedures in the initial diagnostic evaluation and is a useful alternative tool in the long term follow up of patients with ARVC.     

Arrhythmogenic right ventricular dysplasia. Study of a selected population

268 patients (pts) aged between 4 and 63 (average block 33.6) years were examined in an effort to detect structural and/or wall motion abnormalities of the right ventricle, consistent with a diagnosis of Arrhythmogenic Right Ventricular Dysplasia (ARVD). The patients included in this study had some of these features: 1) sudden juvenile death (age less than 35 years) due to heart disease; 2) relatives of pts died suddenly of pathologically proven ARVD; 3) pts with ventricular arrhythmias grade Lown greater than 3, and with QRS morphology mainly of left bundle branch block; 4) pts between the ages of 18 and 40, with negative T waves beyond V2; 5) pts with ventricular arrhythmias of left bundle branch block morphology, and grade Lown greater than 1, and negative T waves beyond V1. ARVD was recognized in 108 living and 18 deceased pts. Our data confirm that ARVD is a wide spectrum disease, going from the classical form described by Marcus and Fontaine to concealed forms characterized mainly by premature ventricular complexes.