Potential link between Helicobacter pylori and ischemic heart disease: does the bacterium elicit thrombosis?

Over the past fifteen years, numerous observations have linked Helicobacter pylori (H. pylori) infection to ischemic heart disease (IHD). Despite the controversial literature data, it has been postulated that if a role is plausible, it will be in the early events of the acute coronary syndrome. According to this model, we focused on the potential pathogenic mechanisms relating H. pylori to IHD like platelet aggregation and thrombosis. To identify all publications in this field, a MEDLINE search of studies published in English from 1965 to 2009 was conducted. Although very few investigations were found, these showed data of paramount importance. In particular, it has been demonstrated that some strains of H. pylori bind von Willebrand factor and interact with glycoprotein Ib to induce platelet aggregation in humans. In experiments from animal models, such infection promoted the formation of platelet aggregates by both a marked increase in the flux of rolling leukocytes and the appearance of platelet and leukocyte-platelet aggregates in gastric venules. This aggregate formation was abrogated by antibodies against specific adhesion molecules (L- and P-selectin). The future challenge is to gain more knowledge in this field and to translate these information into clinical practice.

Clinical and biochemical parameters related to cardiovascular disease after Helicobacter pylori eradication.

AIM: Since the major established risk factors explain the pathogenesis of ischemic heart disease (IHD) in a proportion of cases, it is crucial to search for other causal mechanisms. The possible link between IHD and Helicobacter pylori (H.pylori) infection has been reported. However, the precise mechanism of this potential relationship, by a proinflammatory activity or metabolic disorder, is unclear. In order to investigate this issue, the authors assessed changes in clinical and biochemical parameters related to IHD after bacterial eradication. METHODS: A total of 496 patients (281 males; mean age 59.7+/-2.3) with H.pylori-positive dyspepsia and/or peptic ulcer were studied after cure of the bacterium. H.pylori status was determined by histology or 13C-urea breath testing. Examinations for body mass index, diastolic blood pressure and blood testing (C-reactive protein, fibrinogen, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, fasting glucose) were performed before eradication and annually for up to five years thereafter. For statistical analyses, the Student's t test was performed. RESULTS: HDL-C increased (P=0.02) while C-reactive protein and fibrinogen levels diminished (P<0.0001) significantly. BMI and diastolic blood pressure increased in a significant (P=0.032 and P=0.039 respectively) manner compared to baseline. CONCLUSIONS: H.pylori eradication is associated with modification of some clinical and biochemical parameters related to IHD during a follow-up of five years. There is a need for large interventional randomized studies in order to prove a causal association.

Chest wall and hemidiaphragm reconstruction with Gore-Tex mesh and omolateral latissimus dorsi flap. A case report.

There are various method of reconstruction when chest wall resection is performed for the treatment of tumors of the chest wall. In this case a chest wall resection and reconstruction was performed using an omolateral latissimus dorsi flap, together with Gore-Tex mesh. A 42-year-old woman was diagnosed as having a huge low grade chondrosarcoma and underwent surgical resection which interested the anterior chest wall from the level of the IV to X rib and the right hemidiaphragm. Gore-Tex mesh was fixed to the residual chest wall and an ipsilateral pedicled latissimus dorsi muscle flap was placed on the alloplastic mesh. The patient was discharged from the hospital 17 days postoperatively. The postoperative course was uneventful and the wound was fine.

Is dobutamine stress echocardiography predictive of middle and late term outcomes in mitral stenosis patients?

AIM: In mitral stenosis (MS) patients with a poor symptom-echocardiography correlation, dobutamine stress echocardiography (DSE) still does not have a confirmed utility and predictive value. Our aim is to evaluate usefulness of DSE in assessing 2 and 5 years clinical outcomes. METHODS: Forty-four consecutive patients with known MS were submitted, between April 1998 and July 1999, to basal and DSE. Patients were divided in 2 groups: group A if during DSE was reached a mean mitral gradient (MG) = or > 15 mmHg and/or a pulmonary arterial pressure (PAP) = or > 60 mmHg, and group B if MG and/or PAP were respectively lower than 15 and 60 mmHg. Endpoints considered were death, hospitalization for acute pulmonary edema, complications associated with mitral valve disease and mitral valve interventions (percutaneous or surgical). Mean follow-up was 73.6+/-16.6 months. RESULTS: Mean age was 55.2+/-10.5 years; 83.7% were women; NYHA class was I-II-III respectively in 18.6%, 58.1% and 23.3% of the patients; mean mitral valve area was 1.39+/-0.26 cm2; mean MG 8.05+/-2.54 mmHg; PAP 39.3+/-7.9 mmHg. Twenty-five patients met criteria for group A and 18 for group B. The event-free interval (27.9+/-32.1 months in group A vs 53.5+/-25.8 months in group B; P=0.008) and the 2 years event-free survival (40% for group A vs 88.9% for group B; P=0.002) showed significantly different patterns between the 2 groups. The 5 years survival analysis did not reach significance. CONCLUSION: DSE seems to detect MS patients that will have rapid evolution of their valvular disease within 24 months.

Updated review (2006) on Helicobacter pylori as a potential target for the therapy of ischemic heart disease.

UNLABELLED: Despite knowledge about the classical risk factors for ischemic heart disease (IHD) has increased, all the differences in morbidity as well as mortality from this disease cannot be fully explained. Hence the importance of looking for other causal mechanisms. Numerous infectious agents have been linked to IHD and among these also Helicobacter pylori (H. pylori). However, a number of studies have reported conflicting RESULTS: The present review attempts to highlight on the update pertaining a potential etiologic role of H. pylori infection in the pathogenesis of IHD. Some new evidences have emerged in the last years in literature. While epidemiological approach seems to confirm previous uncertainties (hypothetical role of the bacterium in the acute phase), experiments have demonstrated the presence of bacterial DNA in the plaque. Furthermore, the most encouraging evidence of a possible association emerges from an intervention small trial showing a significant reduction of coronary events after H. pylori eradication. Because IHD is the outcome of a multiciplity of factors, many of which with only a limited individual effect, complete understanding of causation is difficult. It may be possible to identify some factors, such as H. pylori, the effects of which are large enough to be potential target for prevention. This is of major public health importance, since the eradication of the infection is easy and certainly much less expensive than long-term treatment for other risk factors. Prospective population-based studies and interventional trials, focusing on the advantage of the eradication of H. pylori infection on the prevention or the reduction of recurrence in subjects with IHD, should be performed in order to provide support of a causal relationship. This represents a promising direction for future studies.

Surgical revascularization in the ischemic heart disease. Long-term results in a series of consecutive patients selected according to the principles.

AIM: Ischemic heart disease can be treated with drugs, percutaneous coronary interventions (PCI) and surgical revascularization (CABG). In our institution the therapeutic decisions for non emergent cases have been regularly taken during a daily meeting attended by clinicians, interventionalists, and surgeons, who all adhere to the principles of Evidence Based Medicine. The purpose of the present report is to investigate the long-term results in a series of consecutive patients to whom surgical revascularization has been recommended following the abovementioned approach. METHODS: We selected 597 patients with no prior interventions, who were referred to our institution for coronary angiography between January 1991 and December 1997 and to whom surgical revascularization was recommended. The Kaplan-Meier method was adopted to evaluate survival and freedom from: non fatal acute myocardial infarction, PCI, repeat CABG. RESULTS: The results were compared to those of the randomized trials or of large follow-up reports. The mean observation period was 6.8 years. The results at 5 and 10 years were: overall survival 95.5% and 90.2%; freedom from acute myocardial infarction 95.5% and 90.2%; freedom from surgical reintervention 98.6% and 97.1%; freedom from PCI 91.2% and 79.8%; survival free from all events 79.3% and 58.1%. These rates were comparable to those reported by the most important clinical trials. CONCLUSIONS: If surgical treatment for patient with coronary artery disease is recommended according to the suggestions of the leading clinical trials and pertinent guidelines, the results in terms of mortality and morbidity are comparable to those of the trials themselves, even in the non selected patients of daily clinical practice.

The role of gastroesophageal reflux disease in chest pain.

Gastroesophageal reflux disease (GERD) is thought to play an important role in the pathogenesis of non-cardiac, unexplained, chest pain. The physiopathological mechanism of this extraesophageal manifestation, remains unclear but it is supposed that the ache could be triggered by the stimulation of acid-sensitive nociceptors of the mucosa. The esophageal origin of the symptom may be identified by an empiric trial of high-dose antisecretory drugs or an abnormal prolonged ambulatory pH monitoring study. Less important is the role of endoscopy especially in subjects without typical symptoms of GERD. The use of manometry or provocative tests can consent to evaluate for esophageal motility abnormalities. It is generally accepted that in clinical practice, in patients with non-cardiac chest pain, the administration of proton pump inhibitors, could serve as a first approach. It is cost-effective in the short-term period, when compared with investigation for gastrointestinal causes, with cost savings persisting beyond a year. In conclusion, patients with non-cardiac chest pain of unknown origin should be carefully screened for the occurrence of GERD, but further research is needed to clarify the role of the latter on the pathogenesis of this symptom.

Ischemic cardiovascular disease and Helicobacter pylori. Where is the link?

Coronary heart disease (CHD) is the leading cause of death in western countries. Although several major risk factors have been identified, they fail to account for all the epidemiological variants of the disease, thus warranting research into novel causal agents. Cardiovascular diseases have long been associated with chronic infections acting through the activation of inflammatory pathways, and antibiotic therapy has been shown to produce a dramatic decrease in the rate of disease recurrence in patients with a history of myocardial infarction or unstable angina. The link between Helicobacter pylori (H. pylori) infection and CHD, first described by Mendall et al. in 1994, has been the subject of a multitude of epidemiological and clinical studies; however, these have been so heterogeneous that not two of them are based on a comparable selection of patients and focused on the same kind of disease, e.g. stable coronary heart disease or acute myocardial infarction. Evidence from animal studies supports the thesis that H. pylori plays an extremely important role in the acute phase of myocardial infarction: the bacterium causes platelet aggregation and induces pro-coagulant activity in experimentally infected mice. H. pylori may also contribute to atherosclerosis through an auto-immune process against endothelial cells or an increased concentration of homocysteine in the blood due to decreased levels of folic acid and cobalamin. The exact role of H. pylori cannot yet be fully assessed: there is a clear and present need for further studies with appropriate epidemiological and clinical approaches to investigate through prospective and interventional trial the possible causal relationship between H. pylori and CHD.

[Infections and cardiovascular diseases on an ischemic basis. The case of Helicobacter pylori]. / Infezioni e malattie cardiovascolari su base ischemica. Il caso dell'Helicobacter pylori.

Cardiac and cerebrovascular diseases are an important cause of mortality in industrialized countries. "Classical" risk factors cannot fully explain epidemiological variations of these diseases. From several years infections have been linked to ischemic vascular events and recent publications pointed to the role of Helicobacter pylori, a Gram negative bacterium, involved in the pathogenesis of gastritis and peptic ulcer. Results on the association between this bacterium and acute myocardial infarction or stroke are controversial, due to the degree of studies heterogeneity. There is the need for extensive prospectic studies to evaluate the incidence of these diseases in relation to the presence of Helicobacter pylori infection. Interventional randomized studies employing an antibiotic treatment for patients affected by ischemic vascular diseases will rapidly answer the question of wheather Helicobacter pylori has a causal role in the pathogenesis of acute myocardial infarction and ischemic stroke.

[Use of colchicine in chronic pericardial effusion. Presentation of 2 clinical cases and review of the literature]. / Utilizzo della colchicina nel versamento pericardico cronico. Presentazione di due casi clinici e revisione della letteratura.

Colchicine was introduced in 1987 for the treatment of recurrent pericarditis. Up to the present, papers have been published on a total of 117 patients treated with colchicine after the failure of treatment with FANS, corticosteroids and repeated pericardiocentesis. Here two cases of chronic pericardial effusion, one secondary to pericardiotomy, the second idiopathic, are reported. Both were recalcitrant to conventional therapy. Both patients were treated with 2 mg/die colchicine for 1 month followed by 1 mg/die for a further 5 months, without recurrence of the effusion after follow-up of 12 and 24 months respectively. No side-effects were observed. Colchicine is an anti-inflammatory drug which, by inhibiting various leukocyte functions, depresses the action of the leukocytes and of the fibroblasts at the site of the inflammation. We conclude that colchicine is effective in post-pericardiotomic and idiopathic chronic pericardial effusion as already reported in cases of recurrent pericarditis. Given the lack of side-effects, it could be considered as a drug of choice alternatively to FANS and corticosteroids.

Primary pulmonary hypertension.

Primary Pulmonary Hypertension (PPH) is a rare disease that progressively increases pulmonary arterial pressure and pulmonary vascular resistance to the point of right heart failure, in the absence of secondary causes of the disease. The following specific risk factors that can trigger PPH have been identified and examined: appetite depressant drugs, oral contraceptives and hyperuricaemia. Familial PPH transmitted by an incomplete penetrance dominant autosomic mechanism is responsible for about 6% of PPH cases. Recent research groups have identified the gene responsible for familial PPH. Since pulmonary vasoconstriction is the prime cause of PPH, vasodilation of the pulmonary arterial circulation system (using prostacyclin in the form of epoprostenol or iloprost) is the main aim of treatment.

[Functional assessment of mitral stenosis]. / La valutazione funzionale della stenosi mitralica.

The following parameters must be taken into account when assessing the severity of mitral stenosis: symptoms, objective examination, electrocardiogram, chest X-ray, a simple exercise test with or without cardiopulmonary test, echocardiography and lastly a hemodynamic test. Differences are often observed between the clinical and instrumental findings. In these cases a major contribution is made by the use of physical effort in response to both ECG and heart catheterization in order to quantify the patient's functional deficiency and valve response. The latter aspect must be validated using a simultaneous comparison between echocardiography and the hemodynamic test and longitudinal clinical studies.

[Gastroesophageal reflux disease and chest pain]. / Malattia da reflusso gastro-esofageo e dolore toracico.

Gastroesophageal reflux disease (GERD) is highly prevalent in the general population. Heartburn and acid regurgitation are considered the typical presentation of GERD, that however might represent a major pathogenic mechanism in patients with chest pain without coronary artery disease. Chest pain in this instance is often successfully treated with high-dose antisecretory drugs, but the pathogenetic mechanism remains unclear. Further research is needed to clarify the role of GERD on the pathogenesis of chest pain and to ascertain whether a medical or surgical anti-secretory treatment could represent a possible approach. Patients with non-cardiac chest pain of unknown origin should be carefully screened for the occurrence of GERD.

Drug-eluting stent: the emerging technique for the prevention of restenosis.

Percutaneous coronary interventions (PCI) have surpassed coronary artery bypass grafting as the most common means for treating coronary artery disease, because of materials improvement, the use of stent and pharmacotherapy. However, despite the variety of mechanical techniques such as dilatation, debulking or conventional stent implantation, the incidence of restenosis on short and mid-term follow-up is still representing an important limitation to PCI. Restenosis is mainly due to elastic recoil, negative vessel remodelling and neointimal proliferation, as a response to vessel injury induced by angioplasty devices. The use of conventional stents has provided an efficient method to avoid elastic recoil and negative vessel remodelling, thus partially reducing restenosis as compared to conventional balloon dilatation. However, neointimal proliferation (biological vessel response to injury caused by stent implantation) is not affected by stenting technique. Thus, the extensive use of coronary stent, even in complex lesions, have produced again a "new" disease: the in-stent restenosis especially in some patients' subset (diabetics) or in some lesion subset (bifurcations, long lesions, small vessels, total occlusions, diffuse disease). Therefore, the main target of today's interventional cardiologists is to resolve this problem. The combination between mechanical control of elastic recoil and negative remodelling (stent) and the control of neointimal proliferation - biological response to vessel injury - (antiproliferative drugs) is the emerging approach against restenosis. This emerging approach consists in using the stent as drug carrier to the target site. Local delivery of antiproliferative or immunosuppressive agents using a drug-coated stent is supposed to inhibit in stent restenosis. The first antiproliferative agents being used successfully in clinical trials are sirolimus and paclitaxel and, so far, the data available of these trials demonstrated a marked reduction of restenosis using sirolimus- and paclitaxel-coated stents as compared to conventional stents. However, many questions are still to be answered and several other clinical trials with drug-eluting stents are ongoing, evaluating safety and efficacy of sirolimus and paclitaxel in a larger number of patients and in different subset of coronary lesions type and morphology. Based on the very impressive results available at the present time, we can expect, in the very near future, remarkable changes in our clinical practice and the beginning of a new "era" of interventional cardiology.

[A case of pulmonary thromboembolism after interruption of treatment with unfractionated heparin]. / Un caso di tromboembolia polmonare dopo la sospensione del trattamento con eparina non frazionata.

Pulmonary embolism is a quite frequent event (incidence 1/10000/year), and blood stasis, endothelial lesions and coagulation disorders are predisposable factors. Elective treatment is heparin, but the use of this medication is associated with a possible ipercoagulative rebound effect. The case presented is a patient with unstable angina treated with heparin infusion, who developed pulmonary embolism after discontinuation of heparin treatment; the patient didn't present a genetic coagulopathy. Others risk factors have been analyzed and it was observed that discontinuation of heparin infusion could have a predominant role in the development of thrombosis. A MedLine research on the rebound effect of heparin and how to reduce it has been carried out.

[Surgical treatment of atrial thrombosis. A transesophageal echocardiogram study]. / Trombosi atriale trattata chirurgicamente. Valutazione con ecocardiogramma transesofageo.

Transesophageal echocardiogram is the procedure of choice in the evaluation of masses located in the cardiac chambers. In this paper three cases of atrial thrombosis are presented: a) a free floating ball thrombus in the left atrium in a patient with moderate mitral stenosis; b) three thrombotic masses adherent to a central venous catheter; c) three thrombotic masses attached to Chiari s network in a patient operated for an ostium secundum atrial septal defect one year before. In all cases transesophageal echocardiogram has played a key role in the diagnosis. Medical therapy has been inadequate and so surgical removal has been performed. Unsuccessful medical therapy, a new episode of thrombosis, intracardiac permanent catheter infections and high risk of systemic and pulmonary embolism are indications for thrombectomy.

When should asymptomatic patients with combined severe aortic stenosis and aortic insufficiency undergo valve replacement? A clinical case.

Indications to prosthetic aortic valve implantation in patients with aortic stenosis or aortic regurgitation or both stenotic or regurgitant aortic valve, who present without symptoms, are controversial. We present the case of an asymptomatic patient with combined severe aortic stenosis and an equally important insufficiency, undergoing surgery for valve substitution with a bileaflet prosthesis. After surgery he was treated with warfarin according to the doses recommended and underwent follow-up with clinical and echocardiographic exams. Eight months after intervention the patient had an embolic stroke with aphasia and right hemiplegia, despite the therapeutic level of INR. At present, even though he has partly recovered motor function, he reports a noteworthy decline in life quality, because of the persistent speech difficulties. We use this case as the starting point for a discussion of the chance of referring patients affected by aortic valvulopathy to valve substitution, in the absence of symptoms.

[Ischemic cardiovascular diseases. Correlation with Helicobacter pylori infection]. / Patologie cardiovascolari ischemiche. Correlazione con l'infezione da Helicobacter pylori.

Coronary heart disease is the primary cause of mortality in western countries. The well-established ("classical") risk factors cannot fully explain epidemiological variations of this disease. From several years infections have been linked to ischemic vascular events and recent studies pointed to the role of Helicobacter pylori (H. pylori), a spiral Gram negative bacterium, that chronically infects human stomach and is involved in the pathogenesis of gastritis and peptic ulceration. Systematic reviews of studies have suggested the existence of a possible weakly positive association between this bacterium and coronary heart disease, but this could be due to confounding bias and influenced by the degree of investigations heterogeneity. Experiments from animal studies demonstrated that H. pylori infection in mice induces the formation of platelet aggregates and in contrast to Chlamydia pneumoniae it has not been found in the plaque: therefore, the role of H. pylori, could be even more important in the acute phase of myocardial infarction. There is the need for extensive prospective studies to evaluate the incidence of these diseases in relation to the presence of H. pylori infection. Appropriately randomized studies employing an antibiotic treatment for patients affected by ischemic vascular disease will answer the question of whether H. pylori has a causal role in the pathogenesis of acute myocardial infarction and ischemic stroke.

Evolving standard in the treatment of coronary artery disease. Drug-eluting stents.

Coronary stent implantation is the predominant method of percutaneous coronary interventions (PCI). This is to be attributed to the ease of use beside the better short and long term clinical outcome as compared to balloon angioplasty. Nevertheless, improvements in operator skill and stent technology together with better use of adjunctive pharmacological therapy have contributed to the improvement in clinical outcome. However, the main limitation of coronary stenting is still represented by in-stent restenosis (ISR) with an estimated rate of 17-32%. Thus, compared to coronary bypass surgery, the major adverse cardiac events following stent implantation are still higher and mainly represented by the need for re-intervention. The advent of drug eluting stents (DES) has led the experts to predict that with DES there will be little or no difference between PCI and coronary bypass surgery in terms of long-term outcome leading to a further expansion of indications. The clinical trial programs of the 2 available DES for clinical use (sirolimus-eluting stent, SES - Cypher and paclitaxol-eluting stent - Taxus) have been able to demonstrate the safety and clinical efficacy of both. Nevertheless, off-label use in patients on high risk for restenosis confirmed these data. At least for SES as was demonstrated by 2 "real world" registries. Thus, the introduction of DES represents a remarkable evolution for new standards in coronary artery disease treatment and offers hope to those patients considered to be "high risk" such as diabetics, patients with ISR, diffuse disease in whom surgery was previously the only therapeutic option. This paper will discuss the main results of the clinical trial programs of the DES (mentioned above) available for clinical use in the present time and analyze technical and procedural aspects which could affect long term outcome.