Giuseppe Limongelli

Effects of losartan on hypertension and left ventricular mass : a long-term study

This study evaluated the anti-hypertensive efficacy, tolerability and effects on left ventricular mass of losartan, a selective angiotensin II receptor antagonist, after 22 months in patients with essential hypertension. The study included 77 hypertensive patients who were randomised at baseline to 22 months double-blind once-daily treatment with losartan 50u2009mg (L group nu2009=u200944 patients, mean age 54u2009±u20099 years) or hydrochlorothiazide 25u2009mg (HCTZ group, nu2009=u200933 patients, mean age 56u2009±u20097 years). Routine haematology, blood chemistry, standard electrocardiography, echocardiography and ambulatory non-invasive 24-h blood pressure (BP) monitoring were performed at baseline and after 10 and 22 months. The results showed good tolerability and a significant mean systolic and diastolic BP reduction in all groups (L group: 22 mmu2009Hg and 11 mmu2009Hg; HCTZ group: 11 mmu2009Hg and 7 mmu2009Hg, respectively for systolic and diastolic mean BP). Moreover, a remarkable reduction in left ventricular mass index was reached after 10 and 22 months only in the L group (L group: Δu2009=u2009–11u2009g/m2, Pu2009<0.02; hctz group: δu2009=u2009–5 g/m2, Pu2009=u20090.38). In conclusion, losartan was well tolerated and produced a significant reduction in BP and left ventricular mass in hypertensive patients

Prevalence and natural history of heart disease in adults with primary mitochondrial respiratory chain disease

The prevalence and natural history of cardiovascular disease in adult patients with respiratory chain disease (RCD) is poorly characterized. We sought to determine the frequency and natural history of cardiac disease in patients with primary RCD.

Skeletal muscle involvement in cardiomyopathies.

The link between heart and skeletal muscle disorders is based on similar molecular, anatomical and clinical features, which are shared by the ‘primary’ cardiomyopathies and ‘primary’ neuromuscular disorders. There are, however, some peculiarities that are typical of cardiac and skeletal muscle disorders. Skeletal muscle weakness presenting at any age may indicate a primary neuromuscular disorder (associated with creatine kinase elevation as in dystrophinopathies), a mitochondrial disease (particularly if encephalopathy, ocular myopathy, retinitis, neurosensorineural deafness, lactic acidosis are present), a storage disorder (progressive exercise intolerance, cognitive impairment and retinitis pigmentosa, as in Danon disease), or metabolic disorders (hypoglycaemia, metabolic acidosis, hyperammonaemia or other specific biochemical abnormalities). In such patients, skeletal muscle weakness usually precedes the cardiomyopathy and dominates the clinical picture. Nevertheless, skeletal involvement may be subtle, and the first clinical manifestation of a neuromuscular disorder may be the occurrence of heart failure, conduction disorders or ventricular arrhythmias due to cardiomyopathy. ECG and echocardiogram, and eventually, a more detailed cardiovascular evaluation may be required to identify early cardiac involvement. Paediatric and adult cardiologists should be proactive in screening for neuromuscular and related disorders to enable diagnosis in probands and evaluation of families with a focus on the identification of those at risk of cardiac arrhythmia and emboli who may require specific prophylactic treatments, for example, pacemaker, implantable cardioverter-defibrillator and anticoagulation.

Contemporary genetic testing in inherited cardiac disease: Tools, ethical issues, and clinical applications

&NA; Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype–phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, ‘real-world’ experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines.

The Right Heart International Network (RIGHT-NET) : Rationale, Objectives, Methodology, and Clinical Implications

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response.

Management of Bradyarrhythmias in Heart Failure: A Tailored Approach

Patients with heart failure (HF) may develop a range of bradyarrhythmias including sinus node dysfunction, various degrees of atrioventricular block, and ventricular conduction delay. Device implantation has been recommended in these patients, but the specific etiology should be sought as it may influence the choice of the type of device required (pacemaker vs. implantable cardiac defibrillator). Also, pacing mode must be carefully set in patients with heart failure (HF) and left ventricular systolic dysfunction.In this chapter, we summarize the knowledge required for a tailored approach to bradyarrhythmias in patients with heart failure.

Severe hypertrophic cardiomyopathy in a patient with atypical Anderson-Fabry disease

AIMnAnderson-Fabry disease (AFD) is a hereditary disorder caused by a deficiency in the lysosomal enzyme α-galactosidase A which causes dysfunctions in multiple organ systems. Cardiac manifestation includes left ventricular hypertrophy, thickening of the valves, conduction disturbances and in the late phase, extensive areas of myocardial fibrosis with increased risk of sudden cardiac death. Case example: A case of AFD with exclusive cardiac involvement is described. During follow-up, due to the high risk of life-threatening arrhythmic events, implantation of an implantable cardioverter defibrillator is performed.nnnCONCLUSIONnAFD patients with advanced cardiac disease might represent a subgroup of patients who may require an implantable cardioverter defibrillator for primary prevention of sudden cardiac death.

Cardiac manifestations of mitochondrial disorders: reply

With interest we read the article by Limongelli et al. about cardiac involvement (CI) in 32 patients with mitochondrial disorders (MIDs). The study raises concerns. Exercise limitation was found in 24 patients and was exclusively regarded as a cardiovascular symptom. Since 14 patients had exercise intolerance and progressive muscle weakness, since 17 developed muscle fatigue during a metabolic exercise test, and since easy fatigability is generally a dominant phenotypic feature of MIDs, it is conceivable that exercise limitation was at least in part or exclusively attributable to the oxidative defect or weakness of the striated muscles and not exclusively to CI. Although dyspnoea is a frequent manifestation of cardiac disease it can also be a manifestation of affected respiratory muscles. Since eight patients had mitochondrial myopathy, 12 mitochondrial myopathy with ophthalmoplegia, two Kearns–Sayre-syndrome and seven MELAS-syndrome, it cannot be excluded that the respiratory muscles were also affected. Did all patients undergo spirometry to assess the muscular component of dyspnoea? Left ventricular non-compaction, also known as left-ventricular hypertrabeculation, is frequently found in patients with neuromuscular disorders and MIDs. The definition of non-compaction, however, is under debate. According to which criteria was noncompaction diagnosed, and did the patient develop ventricular tachycardia or cardiac embolism, frequent complications of non-compaction? Phenotypic expression of mtDNAmutations largely depends on the relation between the amount of mutated and wildtype mtDNA. What were the mutation rates of the A3243G, A8344G, G9952A, 12294-tRNA, 11232-tRNA, and mtDNAdeletions? Which nucleotide-exchange was associated with the 12294and 11232tRNA-mutations? The A8344G mtDNA-mutation has not been described as the cause of a neuropathy, ataxia, and retitintis pigmentosa (NARP)phenotype. Was this patient also tested for the T8993G/C mutations, which usually cause NARP? Although mitochondrial tRNAmutations may cause chronic progressive ophthalmoplegia it has not been reported together with the 11232 tRNA-mutation. Were these mutations also found in other family members? What was the mutation rate? Did the NARP-patient also develop features of MERRF-syndrome, which is most frequently due to the A8344G mutation? To conclude that life-threatening cardiovascular complications occur rarely is not justified with regard to the number of investigated patients, the duration of follow-up, previous reports about death from CI in MIDs, and the few studies available which address this question. Overall, patients with MIDs need to be closely followed-up for CI, since the rate and frequency of progression is largely unknown and it is unclear if patients profit from preventive measures (CRT/ICD-devices) at an early stage of CI.