Beneficial effects of one-month sacubitril/valsartan treatment in a patient affected by end-stage dystrophinopathic cardiomyopathy

Dystrophinopathic cardiomyopathy (DCM) is an almost constant manifestation in Becker muscular dystrophy (BMD) patients significantly contributing to morbidity and mortality. The nearly complete replacement of the myocardium by fibrous and fatty connective tissue results in an irreversible cardiac failure, characterized by progressive reduction of the ejection fraction. According to PARADIGM-HF trial results, the European Society of Cardiology (ESC) guidelines recommend the use of sacubitril/valsartan in ambulatory patients with heart failure and reduced ejection fraction, who remain symptomatic despite an optimal medical therapy. To date, little is still known about the use of sacubitril/valsartan in DCM. We report the case of a patient with dystrophinopathic end stage dilated cardiomyopathy with reduced ejection fraction who successfully responded to sacubitril/valsartan treatment.Key words: dystrophinopathic cardiomyopathy, heart failure, sacubitril/valsartan, Becker muscular dystrophy     

The athlete's heart: remodeling, electrocardiogram and preparticipation screening

Highly trained athletes show morphologic cardiac changes (ie, athlete's heart) that are the consequence of several determinants, including type of sport, gender, and, possibly, inherited genetic factors. The extent of physiologic cardiac remodeling may occasionally be substantial in highly trained athletes and may raise a differential diagnosis with structural cardiac disease, such as cardiomyopathies. In addition, athletes demonstrate a spectrum of alterations in the 12-lead electrocardiogram (ECG) pattern, including marked increase in precordial R-wave or S-wave voltages, ST segment or T-wave changes, and deep Q waves suggestive of left ventricular hypertrophy, that may raise the possibility of pathologic heart condition, but have also been viewed as a consequence of the cardiac morphologic remodeling induced by athletic conditioning. To evaluate the clinical significance of these abnormal ECGs, the authors compared ECG patterns to cardiac morphology and function (assessed by two-dimensional echocardiography in individual athlete) in a large population of 1005 elite athletes engaged in a variety of sporting disciplines. Forty percent of the athletes had abnormal ECGs, and a subgroup of about 15% showed distinctly abnormal and often bizarre patterns highly suggestive of cardiomyopathies, such as hypertrophic cardiomyopathy, in the absence of pathologic cardiac changes. Such alterations are likely the consequence of athletic conditioning itself and represent another potential component of athlete's heart syndrome. However, such false-positive ECGs represent a potential limitation to the efficacy of routine ECG testing in the preparticipation cardiovascular screening of large athletic populations.     

Risk of progression to AIDS and death in women infected with HIV-1 initiating highly active antiretroviral treatment at different stages of disease

BACKGROUND: The optimal virologic and immunologic stage at which to initiate antiretroviral therapy in individuals infected with human immunodeficiency virus type 1 (HIV-1) is undefined. METHODS: Among 1054 HIV-1-infected women in a prospective cohort study, we determined the time from initiation of highly active antiretroviral treatment (HAART) to acquired immunodeficiency syndrome (AIDS) and death. RESULTS: Median follow-up was 3.4 years. Of 553 women without AIDS at HAART initiation, 62 (11%) developed AIDS. Compared with women with CD4(+) cell counts greater than 350/microL at HAART initiation, women with cell counts of 200 to 350/microL and less than 200/microL had relative hazards (RHs) for progression to AIDS of 0.93 (95% confidence interval [CI], 0.46-1.86) and 2.48 (95% CI, 1.39-4.42), respectively. Compared with those with HIV-1 RNA values less than 5000 copies/mL, women with 5000 to 50,000 copies/mL and greater than 50,000 copies/mL had RHs of 1.39 (95% CI, 0.74-2.64) and 2.09 (95% CI, 1.09-3.99), respectively. Among women with AIDS at HAART initiation (n = 501), RHs of death were 1.97 (95% CI, 0.84-4.66) and 3.35 (95% CI, 1.59-7.08) with CD4(+) cell counts of 200 to 350/microL and less than 200/microL, respectively, relative to those with greater than 350/microL, and 1.90 (95% CI, 0.84-4.30) and 3.70 (95% CI, 1.81-7.54) for those with HIV-1 RNA values of 5000 to 50,000 and greater than 50,000 copies/mL, respectively, relative to those with less than 5000 copies/mL. CONCLUSIONS: Progression to AIDS and death was predicted by pre-HAART values of less than 200/microL for CD4(+) cells and greater than 50,000 HIV-1 RNA copies/mL, indicating that deferral of HAART until the CD4(+) cell count is between 350 and 200/microL is a valid strategy in the clinical management of HIV-1 infection.     

The Perugia hospital-based Stroke Registry: report of the 2nd year

This study reports the characteristics of stroke patients admitted to our hospital in the period Jan 1st, 1998-Dec 31st 1999. Seven hundred and ninety seven consecutive subjects (412 males; mean age 71 +/- 13 years) with a first-ever stroke were registered. Two-thirds of patients (65%) were admitted to the Stroke Unit (SU). The remaining part was managed in six general medicine wards (GM) or other services [neurosurgery and intensive care units (ICU+ NS)]. Ischemic stroke occurred in 534 subjects (67%). The high prevalence (30.1%) of haemorrhages can be partly explained by the presence of specialized neurosurgical services. Athero-thrombotic infarctions occurred in 21.7% of patients, lacunar in 24.7%, cardioembolic in 18.1%, other determined in 6.1%, and other undetermined in 27.5%. Overall hospital mortality was 10%. In cerebral hemorrhage mortality was 18% (44/240) vs. 6.3% (32/534) in ischemic stroke (p < 0.05). The distribution of stroke types and mortality was similar to other previous reports.     

Exocrine pancreatic cancer,cigarette smoking,and diabetes mellitus: a case-control study in northern Italy

The role of cigarette smoking and diabetes mellitus as risk factors for exocrine pancreatic cancer (PC) was investigated in a hospital based case-control study. Current smokers were at increased risk for PC (OR = 2.36, 95% CI 1.53-3.63): the magnitude of the risk was related to the lifetime amount of smoking (chi2(trend) = 17.00; P < 0.0001). Among former smokers, after 15 years from ceasing smoking, the risk for PC dropped to the level of a lifetime non-smoker, whichever the lifetime smoking amount. Diabetes was associated with a 2.89-fold increased risk for PC (95% CI 1.71-4.86): the risk was 4.76 (95% CI 1.99-11.53) for diabetes diagnosed up to 2 years before the diagnosis of PC and dropped to 2.07 (95% CI 1.02-4.20) for diabetes diagnosed more than 5 years before PC. The risk for PC was estimated according to the treatment used to control diabetes: it was 6.49 (95% CI 2.28-18.48) for insulin treated diabetes and 2.12 (95% CI 1.16-3.87) for diabetes treated with oral hypoglycemic drugs. The risk of PC for diabetes treated for more than 5 years before the diagnosis of PC was 6.21 (95% CI 1.61-23.96) for patients treated with insulin and 1.21 (95% CI 0.50-2.92) for those treated with oral hypoglycemic drugs: the type of treatment needed to control the disease may discriminate between the diabetes that represents a consequence of cancer from the diabetes that could represent an etiological co-factor. More studies are needed to clarify whether long-lasting insulin-treated diabetes is an etiological co-factor in PC.     

Microvascular Dysfunction, Myocardial Ischemia, and Progression to Heart Failure in Patients with Hypertrophic Cardiomyopathy

Microvascular dysfunction can be demonstrated in most patients with hypertrophic cardiomyopathy (HCM), both in the hypertrophied and nonhypertrophied myocardial walls, mostly due to intimal and medial hyperplasia of the intramural coronary arteries and subsequent lumen reduction. As a consequence, regional myocardial ischemia may be triggered by exercise, increased heart rate, or arrhythmias, in areas which are unable to increase myocardial blood flow. In patients with HCM, microvascular dysfunction leading to severe myocardial hypoperfusion during maximal hyperemia represents a strong predictor of unfavorable outcome, left ventricular remodeling with progressive wall thinning, left ventricular dysfunction, and heart failure. Accurate quantitative assessment of microvascular dysfunction and myocardial ischemia is not easily feasible in clinical practice. Although signs of inducible myocardial ischemia may be detected by electrocardiogram, echocardiography, or myocardial scintigraphy, the vasodilator response to dipyridamole by positron emission tomography is considered the method of choice for the assessment of maximal regional and global flow. Cardiac magnetic resonance provides further information, by late gadolinium enhancement (LGE), which may show areas where replacement fibrosis has occurred following microvascular ischemia and focal necrosis. LGE areas colocalize with severe regional microvascular dysfunction, are associated with increased prevalence of ventricular arrhythmias, and show more extensive distribution in the late stages of the disease, when heart failure is the dominant feature. The present review aims to provide a concise overview of the available evidence of microvascular dysfunction and ischemia eventually leading to disease progression and heart failure in HCM patients.     

Positron emission tomography (PET): evaluation of chronic periaortitis

OBJECTIVE: To evaluate the presence and extent of large-vessel inflammation in patients with chronic periaortitis (CP) using (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: A consecutive case series consisting of 7 patients with CP seen over a 3-year period and a control group of 14 patients with malignancy were evaluated with FDG-PET. For every case we selected 2 age- and sex-matched controls who underwent PET imaging for malignancy. The diagnosis of CP was made by means of computed tomography. PET imaging was performed at diagnosis before therapy was started. Measurement of vascular uptake was graded using a 4-point semiquantitative scale. RESULTS: All patients had evidence of grade 2+ or 3+ vascular uptake in the abdominal aorta and/or iliac artery. No controls showed vascular uptake greater than 1+. Vascular uptake in the thoracic aorta and/or in its branches was seen in 3 (43%) of 7 patients. Vascular uptake in abdominal aorta and/or iliac artery was observed in patients with CP but not in controls (100% versus 0%). There was also a significantly more frequent FDG uptake in the large thoracic arteries in case-patients compared with controls (43% versus 0%; P = 0.03). CONCLUSION: FDG-PET scan shows in patients with CP the presence of a large-vessel vasculitis involving abdominal aorta and common iliac arteries, which in some patients is also extended to thoracic aorta and/or its branches.     

Atrial fibrillation recurrence after drug-induced typical atrial flutter ablation.

BACKGROUND: Catheter ablation of typical atrial flutter (AFL) occurring in patients who take antiarrhythmic drugs for atrial fibrillation (AF) has been proposed as a curative approach for AF. The aim of this study was to evaluate the efficacy of this technique. METHODS: Forty-six consecutive patients (30 males, 16 females, mean age 67 +/- 9 years) with paroxysmal or persistent AF were submitted to right atrial isthmus ablation: 1) 33 patients (group 1) in whom typical AFL spontaneously occurred during oral treatment with propafenone (n = 19), flecainide (n = 9) or amiodarone (n = 6); 2) 13 patients (group 2) submitted to electrophysiological study while taking oral propafenone (n = 3), flecainide (n = 8) or amiodarone (n = 1), in whom sustained AFL was induced (n = 9) or AF was induced and AFL was obtained by intravenous administration of class IC drugs (n = 4). The same antiarrhythmic drug which induced the conversion of AF into AFL was administered after ablation. RESULTS: During a follow-up of 20 +/- 18 months (range 1-78 months), 23 patients (50%) remained asymptomatic and free from AF recurrences. Fifteen patients (33%) with AF recurrences reported a reduction in arrhythmia-related symptoms. Eight patients (17%) did not show symptomatic improvement. These results did not significantly differ between group 1 and group 2. The duration of follow-up was significantly longer in patients with AF recurrence. Among several clinical, echocardiographic and electrophysiological parameters, only atrial enlargement and the absence of structural heart disease were independently associated with AF recurrence. CONCLUSIONS: In selected patients with AF and drug-induced AFL, right atrial isthmus ablation and prosecution of the drug treatment is a safe and feasible approach, which totally eliminates or reduces symptomatic AF recurrences in one half and one third of patients, respectively. However, the number of AF-free patients tends to decrease over time.