Giuseppe Cocco

Behçet’s Disease: an Insight from a Cardiologist’s Point of View

Behcets disease (BD) is an enigmatic inflammatory disorder, with vasculitis (perivasculitis) underlying pathophysiology of its multisystemic affections. Venous pathology and thrombotic complications are hallmarks of BD. However, it has been increasingly recognized that cardiac involvement and arterial complications (aneurysms, pseudoaneurysms, rupture and thrombosis) are important part of the course of BD. Pericarditis, myocardial (diastolic and/or systolic dysfunction), valvular and coronary (thrombosis, aneurysms, rupture) involvement, intracardiac thrombi (predominantly right-sided) are, probably, the most frequent cardiac manifestations. Treatment of cardiovascular involvement in BD is largely empirical and aimed at suppression of vasculitis. The most challenging seems to be the treatment of arterial aneurysms and thromboses due to the associated risk of bleedings. Cardiologists should always bear in mind potential threats of (a)symptomatic cardiovascular involvement in BD.

Myocardial Ischemia in Wegener's Granulomatosis: Coronary Atherosclerosis Versus Vasculitis

Wegener’s granulomatosis (WG) is one of the most common small- and medium-sized necrotizing vasculitides that mainly affects the upper and lower respiratory tract and the kidneys. Cardiac manifestations in WG are relatively rare, and their role and place among different causes of mortality remain largely unknown. Substantially increased number of reports describing involvement of all structures of the heart, which underlie conduction disturbances, valvular disease, ischemic heart disease and other potentially serious conditions, underscores importance of comprehensive cardiovascular investigations and monitoring of patients with WG. The majority of previous reports and our current observation distinguish coronary vasculitis and thrombosis as a cause of myocardial ischemia and cardiovascular co-morbidities in WG. It seems plausible that inflammatory processes in this disease, like in some other systemic vasculitidies, do not predispose to accelerated atherogenesis. However, characteristic small- and medium-sized vasculitis still can manifest as myocardial ischemia and infarction. We overview diverse cardiac manifestations and present our own rare case of angina in the oligosymptomatic debut of WG. Importantly, in this case, coronarography failed to reveal atherosclerotic disease or thrombotic occlusion. However, magnetic resonance imaging (MRI) with adenosine test revealed subendocardial ischemia. As a result of immunosuppressive therapy with a steroid and cyclophosphamide, myocardial ischemia disappeared.

Comparison between ivabradine and low-dose digoxin in the therapy of diastolic heart failure with preserved left ventricular systolic function.

Multicenter trials have demonstrated that in patients with sinus rhythm ivabradine is effective in the therapy of ischemic heart disease and of impaired left ventricular systolic function. Ivabradine is ineffective in atrial fibrillation. Many patients with symptomatic heart failure have diastolic dysfunction with preserved left ventricular systolic function, and many have asymptomatic paroxysmal atrial fibrillation. Ivabradine is not indicated in these conditions, but it happens that it is erroneously used. Digoxin is now considered an outdated and potentially dangerous drug and while effective in the mentioned conditions, is rarely used. The aim of the study was to compare the therapeutic effects of ivabradine in diastolic heart failure with preserved left ventricular systolic function. Patients were assigned to ivabradine or digoxin according to a randomization cross-over design. Data were single-blind analyzed. The analysis was performed using an intention-to-treat method. Forty-two coronary patients were selected. In spite of maximally tolerated therapy with renin-antagonists, diuretics and β-blockers, they had congestive diastolic heart failure with preserved systolic function. Both ivabradine and digoxin had positive effects on dyspnea, Nterminal natriuretic peptide, heart rate, duration of 6-min. walk-test and signs of diastolic dysfunction, but digoxin was high-statistically more effective. Side-effects were irrelevant. Data were obtained in a single-center and from 42 patients with ischemic etiology of heart failure. The number of patients is small and does not allow assessing mortality. In coronary patients with symptomatic diastolic heart failure with preserved systolic function low-dose digoxin was significantly more effective than ivabradine and is much cheaper. One should be more critical about ivabradine and low-dose digoxin in diastolic heart failure. To avoid possible negative effects on the cardiac function and a severe reduction of the cardiac output the resting heart rate should not be decreased to <65 beats/min.

Sufficient Weight Reduction Decreases Cardiovascular Complications in Diabetic Patients with the Metabolic Syndrome

Background: The metabolic syndrome is associated with an increased risk of cardiovascular complications. Especially patients with evident cardiac pathology are at high risk for further complications. A sufficient weight reduction would improve the metabolic pathology and reduce the cardiovascular risk. Unfortunately, overweight and obese patients, even with complicated coronary heart disease, do not alter lifestyles regarding fat intake and physical activity, and in a quarter of these patients body weight increases in the follow-up period. Nonetheless, these patients need a weight reduction to be protected from further cardiovascular complications. Therefore, in overweight patients with insulin resistance in whom lifestyle recommendations have failed, orlistat has been used as an adjunct to decrease significantly overweight and to improve the metabolic pathology without increasing mortality. In our opinion, orlistat could also be an adjunct to lifestyle changes in adipose, diabetic patients with the metabolic syndrome and established heart pathology and signs of incipient cardiac dysfunction. Furthermore, we hypothesize that following a sufficient weight reduction improvements in metabolic pathology and, more important to us, in cardiac dysfunction should be observed. Methods: We selected 90 adipose patients with the metabolic syndrome, diabetes type 2, hypertension, mostly with coronary heart disease and concomitant cardiac dysfunction. Cardiac dysfunction was stated when the amplitude of dyspnea was greater than class 2 of the New York Heart Association (NYHA) and when resting left ventricular ejection fraction (LVEF) was <50%. Patients attended standardized nutritional counseling sessions. The caloric restriction was sufficient to create a deficit of 500 calories per day with <30% of total calories derived from fat. All patients were also enrolled in a standardized physical program and were also encouraged to walk briskly for at least 30 min per day. Patients were divided into two groups. Orlistat (120 mg t.i.d.) and placebo (1 capsule t.i.d.) were administered according to a double-blind protocol. Results: Baseline pathology was similar in the two groups, with the exception of hemoglobin (Hb) A1C, which was slightly higher in the orlistat group, the difference being statistically significant (p = 0.031). Unfortunately, lifestyle changes (diet and exercise) induced only small changes with respect to overweight in the placebo group (no orlistat). The metabolic pathology and the cardiac dysfunction did not improve. As expected, in the other group treated with orlistat in addition to lifestyle changes, weight and body mass index decreased significantly (p < 0.001 and p = 0.013, respectively). In parallel the metabolic pathology, especially dyslipidemia, was significantly reduced. Total cholesterol, LDL cholesterol, and triglycerides decreased, while HDL cholesterol increased. These changes were very significant (p < 0.001, p = 0.001, p = 0.001 and p < 0.001, respectively). Uricemia decreased slightly (p = 0.043). The diabetic pathology was also reduced. Insulin sensitivity increased in both groups, but the within group difference was not significant (p = 0.093). Glycemia and Hb A1 decreased, and serum insulin increased. These changes were significant (p = 0.005, p = 0.001 and p = 0.003, respectively). With orlistat treatment, systolic (SBP) and diastolic blood pressure (DBP) and heart rate decreased. The differences from placebo were small but statistically significant (p = 0.025, p = 0.012 and p = 0.039, respectively). As hypothesized, in the orlistat group dyspnea decreased (NYHA class improved) and the LVEF increased from 47.47 ± 3.74 to 51.76 ± 3.66%, and this difference was highly significant compared to placebo (p < 0.001). Conclusions: Unfortunately, recommendations regarding lifestyle changes (diet counseling and physical exercise) may be insufficient to reduce overweight even in patients who need this effect. On the other hand, atherogenic dyslipidemia and glycemia can be decreased with an adequate weight reduction. Our data show that a weight decrease of only 5.6 kg is sufficient to improve significantly atherogenic dyslipidemia, even if most patients remain obese since hemodynamics and cardiac function are improved. We would prefer to obtain these effects by lifestyle changes (increased physical activity and reduced caloric intake combined with a reduced fat consumption). But when these efforts fail to achieve an effect, orlistat may be a valuable adjunct to achieve these goals. Of course this drug should not be given indefinitely, because the long-term effects on the absorption of fat vitamins are poorly known and potentially dangerous.

Cardiac complications in rheumatoid arthritis in the absence of occlusive coronary pathology

Cardiovascular disease is the leading cause of premature mortality in patients with rheumatoid arthritis (RA). Pathophysiology of rheumatoid cardiovascular phenomenon is not fully understood, but systemic inflammation is thought to play a crucial role in the endothelial damage and accelerated course of atherosclerotic disease. Rheumatoid inflammation can also cause coronary pathology and heart failure. We present a case of transient cardiomyopathy in RA in the absence of occlusive coronary pathology, which mimics acute coronary syndrome.

Assessing the benefits of natriuretic peptides-guided therapy in chronic heart failure.

Heart failure (HF) is a major public heart burden among the ageing population. Optimizing management of patients remains challenging despite many advances in therapy for this pathology. Natriuretic peptides (NPs) are related to cardiac morbidity and mortality and their use in guiding treatment might help. Most data on the value of NPs-guided therapy in chronic HF came from centers with high experience in the therapy of HF. Ninety percent of patients had preserved left ventricular function. The story is just too complex to have the final answer. The numbers of treated patients is insufficient to allow a final decision. Most data derive from centers with high skills and were obtained with different assays, different protocols. Many questions are open. Can similar results be obtained in less specialized centers? It is undecided which NP should be used and how high should be the levels to guide the therapy. Which patients might especially benefit from this approach? Is the approach useful in patients with reduced systolic function? Is the strategy as useful in the elderly as in younger patients? In spite of these limitations, available data suggest that it is reasonable to consider the use of NPs to guide the therapy of HF with preserved systolic function. In order to answer some of the questions, a multicenter, prospective study began in January 2013. However, NP guided therapy in chronic HF will only find acceptance in clinical practice if its use results in therapeutic consequences.

Angina pectoris in patients without flow-limiting coronary artery disease (cardiac syndrome X). A forest of a variety of trees.

Coronary heart disease (CHD) represents an important problem worldwide. At present, more women than men are evaluated for CHD and it has been recognized that the prevalence of this pathology in women is at least the same as in men. We have learned that cardiac syndrome X (CSX) is frequent because worldwide each year millions of people (mostly women) with angina pectoris without flow-limiting epicardial pathology are identified. Data from large myocardial infarction registries suggest a 5% to 25% prevalence of cases without flow-limiting coronary pathology. It must, however, be considered that these people are said to have normal coronary arteries by visual analysis of biplane coronarography. On the other hand, as demonstrated from autopsy, and in vivo by ultrasound intravascular studies, it would be more appropriate to say that in the majority of these cases no obstructive or flow-limiting coronary pathology was detected by coronarography. In CSX, endothelial dysfunction and microvascular dysfunction, sometimes with coronary microvascular spasm and epicardial coronary artery spasm, have been recognized as pathophysiologic mechanisms. In CSX, symptoms and pathologic signs are the same in patients with flow-limiting coronary pathology. The difference lies in the fact that the mechanisms of myocardial ischemia are microvascular and flow-limiting epicardial coronary pathology is absent. By interplay, the pathologic entities at work in CSX are linked with poor long-term outcome. The prevalence of these outcomes is probably smaller than in patients with flow-limiting coronary pathology but we lack precise values. Nonetheless, severe cardiovascular complications are frequent in CSX and it is thus the pathology is not benign. Drugs used in coronary ischemic disease are empirically prescribed to treat CSX, but we lack data from specific trials. It seems that statins and ranolazine might exert positive effects. However, specific research to target interventions in CSX would be necessary.

New concepts in the therapy of atrial fibrillation

Atrial fibrillation is a frequent arrhythmia with increasing prevalence. The paper reviews the most important present aspects and paradigms in the treatment of the arrhythmia. The main aim of treatment is directed to improve the quality of life while reducing morbidity and mortality. A large experience derived from epidemiological registers and clinical research, impressive advances in interventional electrophysiological therapies and the introduction of non-vitamin K antagonists had a dramatic impact on the medical approach. Recommended steps to classify and treat atrial fibrillation are presented and discussed.

Cardiac pathology and modern therapeutic approach in Behçet disease

Behçet disease (BD) is an enigmatic inflammatory disorder with multisystemic complications which is endemic in some countries but can be seen in the entire world. Valid diagnostic criteria are available. The pathology is related to a specific perivasculitis with involvement of both arteries and veins of all sizes. Minor arterial and cardiac involvement is frequent in BD but is usually asymptomatic. In exceptional cases cardiac symptoms may be the 1st manifestation of BD. The prevalence of severe cardiac complications (cardio-Behçet) should be < 10%. An impressive therapeutic improvement has been achieved by using appropriate catheterization techniques, coronary and intra-arterial stents, colchicine, drug-response modifying drugs and immunotherapy but, still cardio-Behçet has a poor prognosis. Efforts are undertaken to improve morbidity and prognosis with the use of newer drugs. An important part of the complications in BD are related to the frequent thromboembolic complications and there is high possibility that newer oral anticoagulants will be superior to the classical anticoagulants presently used. Available biologic agents have already been frequently used and seem to have improved the prognosis, but efforts are undertaken to find newer biologic agents with better therapeutic performance and less side-effects. Summarizing as much as possible the effects of the presently used biotherapy in BD, interferon-alpha is effective against many ocular, genital and perhaps vascular manifestations, but its effectiveness is limited by frequent adverse-effects (even if not dangerous for the cardiovascular system). Infliximab is a valid option in the therapy of ocular and cutaneous manifestations but it is less convincing in the therapy of vascular manifestations in vascular- and neuro-Behçet; furthermore, side-effects, including severe cardiovascular complications, are seen in a minority of patients; perhaps worse, infliximab seems to loose efficacy in the long-term therapy, while pharmacogenetics and receptor polymorphism may explain the existence of non-responders and the occurrence of resistance. Adalimumab might be a promising alternative for infliximab and seems to exert a good effect in an eurysmatic and other vascular complications. However, we lack long-term studies. Other biologic agents have been used only in few cases and it is too early to say if they offer new therapeutic perspectives.

Behcet's Disease: an Insight from a Cardiologist's Point of View~!2009-11-07~!2009-12-07~!2010-02-22~!

Behçets disease (BD) is an enigmatic inflammatory disorder, with vasculitis (perivasculitis) underlying pathophysiology of its multisystemic affections. Venous pathology and thrombotic complications are hallmarks of BD. However, it has been increasingly recognized that cardiac involvement and arterial complications (aneurysms, pseudoaneurysms, rupture and thrombosis) are important part of the course of BD. Pericarditis, myocardial (diastolic and/or systolic dysfunction), valvular and coronary (thrombosis, aneurysms, rupture) involvement, intracardiac thrombi (predominantly right-sided) are, probably, the most frequent cardiac manifestations. Treatment of cardiovascular involvement in BD is largely empirical and aimed at suppression of vasculitis. The most challenging seems to be the treatment of arterial aneurysms and thromboses due to the associated risk of bleedings. Cardiologists should always bear in mind potential threats of (a)symptomatic cardiovascular involvement in BD.