Pulmonary arterial hypertension is characterized by an increase in pulmonary vascular resistance. It may occur in diverse clinical settings, such as congenital heart disease, chronic lung disease, connective tissue disease, or could be idiopathic. Pulmonary arterial hypertension may cause significant morbidity and mortality. Iloprost is a stable prostacyclin analog with vasodilatory properties. To overcome its systemic side effects, the inhaled route has been used to obtain pulmonary selectivity. We herein report an unusual case of a cutaneous reaction to continuous inhaled iloprost. To our knowledge, there are scarce case reports on cutaneous side-effects of inhaled iloprost in the pediatric population. The objective of this clinical case report is to highlight this unusual reaction to avoid incorrect diagnoses and treatments.
Oxidative stress, such as increased hydrogen peroxide (H 2 O 2 ) levels, is a major event initiating pathogenesis of various cardiovascular diseases.The effects of Caffeic Acid Phenethyl Ester (CAPE), a natural antioxidant compound, on oxidative stress-induced cardiac cell damage and vascular/heart dysfunction have not been fully elucidated.In this study, the effects of CAPE were tested in H 2 O 2 -induced H9c2 cell damage, a hind limb ischemia (I, 30 min)/reperfusion (R, 60 min), and a global heart ischemia (I, 30 min)/reperfusion (R, 60 min) conditions.We found that H 2 O 2 (300 -700 μM; n=8) concentration-dependently decreased H9c2 cell viability accompanied with increased intracellular reactive oxygen species (ROS).H 2 O 2 (500 μM) significantly decreased cell viability to 23 ± 3% with a significantly increased intracellular ROS levels by 2.95 ± 0.6 fold when compared to the control (both p<0.05).By contrast, co-treatment of CAPE (10 to 40 μM) and 500 μM H 2 O 2 (n=5) significantly improved cell viability associated with reduction of intracellular ROS in a concentration-dependent manner (p<0.05).Similarly, CAPE (0.95 mg/Kg, equivalent to 40 µM in blood, n=5) when given at reperfusion significantly reduced blood H 2 O 2 levels during reperfusion compared to saline treatment in a rat hind limb I (30 min)/R (60 min) model (all p<0.05).Last, CAPE (40 μM, n=5) given at beginning of reperfusion for 5 minutes significantly salvage heart tissue and cardiac contractile function when compared to untreated I/R hearts (n=11; all p<0.05) during 60 min.reperfusion.The cardio-protective effects of CAPE were significantly abolished by a non-selective nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (50 μM, n=5), or a heme oxygenase-1 inhibitor, SnPPIX (20 μM, n=5) (all p<0.05).These results suggest that CAPE mitigates H 2 O 2 caused cardiac cell damage and I/R induced vascular and heart dysfunction possibly by reducing oxidative stress and/or increasing heme oxygenase-1 and nitric oxide synthase activity.
During myocardial ischemia/reperfusion (I/R), the generation of reactive oxygen species (ROS) contributes to post‐reperfusion cardiac injury and contractile dysfunction. Activation of protein kinase C epsilon (PKC ɛ) during I/R has been shown to increase ROS release, in part, by its stimulation of increased uncoupled endothelial nitric oxide synthase activity. We hypothesize that using a cell permeable PKC ɛ peptide inhibitor (PKC ɛ‐) (N‐myr‐EAVSLKPT, MW=1054 g/mol, 10μM or 20μM) will improve post‐reperfused cardiac function and attenuate infarct size compared to untreated controls in isolated perfused rat hearts subjected to I(30 min)/R(90 min). Male Sprague‐Dawley rats (275–325 g) were anesthetized with sodium pentobarbital (60 mg/kg) and anticoagulated with heparin 1000 units IP. PKC ɛ‐was dissolved in Krebs' buffer and infused during the first 10 min of reperfusion. PKC ɛ‐treated hearts exhibited significant improvement in post‐reperfused cardiac function at 90 min in the maximal rate of left ventricular developed pressure (+dP/dt max ): 56±5%; n=6 (10μM) and 46±3%; n=4 (20μM) compared to untreated controls (n=6) which only recovered to 32±5% of baseline values for +dP/dt max respectively (p<0.05). Furthermore, PKC ɛ‐treated hearts showed significant reduction in infarct size of 27±2% (10μM) and 28 ±2% (20μM) compared to untreated control I/R hearts, 40±3% (p<0.05). The results suggest that PKC ɛ‐is effective in improving cardiac function and reducing infarct size and is a putative treatment that could aid in clinical myocardial infarction/organ transplantation patient recovery. Support or Funding Information This study was supported by the Center for Chronic Disorders of Aging, the Division of Research and the Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.
AIM:The purpose of the study was to localize matrix metalloproteinase (MMP)-14, -9, and -2 in the A7r5 smooth muscle cell and to understand the interaction between these MMPs and the cytoskeleton. This interaction was observed under non-stimulating and phorbol 12, 13-dibutyrate (PDBu)-stimulating conditions.METHODS:Confocal microscopy was utilized to define the localizations of MMPs and tissue inhibitor of matrix metalloproteinases (TIMPs) in the A7r5 cell and to determine interaction between MMPs and the cytoskeleton. Under PDBu-stimulating conditions, the presence of MMP active forms and activity by gel zymography was evaluated in the A7r5 cell. Actin and microtubule-polymerization inhibitors were used to evaluate MMP interaction with the cytoskeleton and the cytoskeleton was observed on matrix and within a Type I collagen gel.RESULTS:MMP-14, -9, and -2 were localized to the podosome in the A7r5 smooth muscle cell and interactions were seen with these MMPs and the actin cytoskeleton. PDBu-stimulation induced increases in the protein abundance of the active forms of the MMPs and MMP-2 activity was increased. MMPs also interact with a-actin and not β-tubulin in the A7r5 cell. Galardin, also known as GM-6001, was shown to inhibit podosome formation and prevented MMP localization to the podosome. This broad spectrum MMP inhibitor also prevented collagen gel contraction and prevented cell adhesion and spreading of A7r5 cells within this collagen matrix.CONCLUSION:MMPs are important in the formation and function of podosomes in the A7r5 smooth muscle cell. MMPs interact with a-actin and not β-tubulin in the A7r5 cell. Podosomes play an important role in cell migration and understanding the function of podosomes can lead to insights into cancer metastasis and cardiovascular disease.
Background: Postoperative Atrial Fibrillation (POAF) is the most common complication of open cardiac surgery related to prognosis and morbidity.However, it is controversial whether POAF is associated with excess mortality independent of associated risk factors after cardiac surgery.Methods and results: POAF was identified in 425 patients (34.5%) of 1229 patients underwent isolated valve repair and/or replacement operation.Patients have more chances to experience POAF if they were older than 65 years old (p < 0.0001), Caucasian (p=0.0017), with heart failure (NYHA Class >= III) (p<0.001), with hypertension (p<0.001) or with peripheral vascular diseases (p<0.001).The unadjusted fiveyear survival rate was 82.8% for patients without POAF and 71.3% for with POAF (p < 0.0001).An unadjusted hazard ratio for POAF was 1.85 (95% CI: 1.40 to 2.43).With a propensity score-matching model, in the 406 pairs of patients under adjusted survival analysis showed significant lower survival rate in POAF (p=0.001) with the adjusted hazard ratio of 1.40 (95% CI: 1.01 to 1.92), compared to without POAF. Conclusion:Our present study supported that POAF is independently associated with an increased long-term mortality in patients who had isolated valve surgery.All isolated valve surgery patients without history of atrial fibrillation between January 1997 and December 2007 in Texas Heart Institute Research Database (THIRD) were included for this study.This study was approved by the hospital Institutional Review Board.Data was abstracted with the key words of "valve repair", "valve replacement", and "atrial fibrillation".Postoperative atrial fibrillation was defined as patient who has a new onset of atrial fibrillation/flutter of any duration between operation and discharge with a diagnosis documented by physician.All cause of death was collected and followed for up to 5 years.Patients without feedback were excluded.All of variables were identified from database.The risk factors that are associated with POAF included: Age, Gender, Race,
Background: Subclinical hypothyroidism (SCH) is underdiagnosed in patients (pts) with heart disease, however, there has been controversy surrounding whether it is a cardiovascular risk factor or not.To determine the prognostic significance of SCH in Heart Failure (HF) with Preserved Ejection Fraction (HFpEF) we followed a cohort of pts for 9 years. Methods:In this retrospective cohort, we queried our HF data base to identify HFpEF pts diagnosed in 2006 (registry initiation date) based on symptoms, BNP, and Echocardiogram with no history of hypothyroidism.Primary outcome was cardiovascular disease (CVD) mortality.Subjects divided into 2 groups based on presence or absence of SCH.SCH was defined as TSH of 5-10 mIU/L and normal free T4 in the absence of symptoms or hypothyroidism history. Results:We identified 249 eligible pts, of who 71 had SCH (28.5%).Mean age was 72.1 ± 13.4 years.Women constituted 56.6%.Follow up was for 8.75 ± 0.17 years.The CVD mortality rate for SCH pts was 29.6% versus 14.9 % for the others (P=0.008).The median survival time for SCH pts was significantly lower than pts with normal thyroid function, 99.9 ± 2.9 and 107.7 ± 1.5 months, respectively (P = 0.008 after adjustment for age, sex, hypertension, and other risk factors) (Figure 1). Conclusion:SCH is a significant predictor of mortality in HFpEF pts, despite controlling for some major risk factors.Therefore a mild asymptomatic elevation in TSH has a significant impact on outcome.
Aims: Cardiac resynchronization therapy (CRT-P) and atrioventricular node (AVN) ablation are a recommended treatment option for patients with atrial fibrillation (AF) refractory to medical treatment or pulmonary vein isolation.Its impact on cardiac function and patient outcome in patients with narrow QRS complex and LVEF > 35%, however, remains controversial.The aim of our study was to analyse the impact of CRT-P implantation and AVN ablation on NYHA class, left ejection fraction, EHRA score and left atrial diameter in high symptomatic patients with permanent or paroxysmal AF with narrow QRS complex and LVEF > 35%.Methods: A database of 24 consecutive patients with permanent AF who underwent AVN ablation after CRT-P implantation was analyzed retrospectively.All patients suffered from symptomatic permanent or paroxysmal AF refractory to medical rhythm and rate control or pulmonary vein ablation.Coronary and valvular heart disease was excluded in all patients.Follow up examinations were scheduled on regular intervals after 3 months up 4 years after AVN ablation.Left ventricular ejection fraction (LVEF), left atrial diameter (LAD), NYHA class, EHRA score and pro-BNP-level before procedures were compared to corresponding data on follow-up.Results: LVEF increased from 45.17 ± 10.95% to 53.63 ± 8.33% after CRT-P implantation and AVN ablation, NYHA class decreased 2.33 ± 0.64 to 1.21 ± 0.42, EHRA score decreased from 3.00 ± 0.51 to 1.13 ± 0.34.LAD decreased from 52.04 ± 3.39 mm to 48.96 ± 3.98 mm and pro-BNP decreased from 1257.38 ± 966.40 pg/ml to 579.04 ± 347.69 pg/ml.All changes were significant (p < 0.001). Conclusion:In this retrospective single-centre analysis, we provide striking evidence for significant functional improvement und symptomatic benefit in patients with symptomatic and refractory atrial fibrillation with narrow QRS complex and LVEF > 35% after CRT-P implantation and AVN-ablation procedures.ventricular contractility in patients with AF after AVN ablation.The effect of biventricular pacing in these patients, on the other hand, remains controversial.The heart rate control achieved with AV-junction ablation improved quality of life and exercise capacity with all modes of pacing in patients with severely symptomatic atrial fibrillation [4].In contrast, some studies found biventricular pacing superior to right or left single-ventricular pacing regarding LVEF improvement or NYHA class changes in patients with permanent atrial fibrillation [5].Biventricular pacing is a well-accepted therapy for patients with chronic severe heart failure (LVEF < 35%), QRS > 120 ms and NYHA class III or IV.Many prospective studies [6,7] showed improvement of LVEF and NYHA class after CRT implantation in heart failure patients.Its efficacy in patients with atrial fibrillation and heart failure, however, is limited due to reduced percentages of biventricular pacing.In fact, it has been described that only those heart failure patients with AF, who underwent AVN ablation, showed sustained long-term improvements in cardiac contractility [8] and favorable outcome [9].A meta-analysis [10] revealed improved outcome in AF patients with CRT implantation and insufficient biventricular pacing that underwent AVN ablation compared to those who did not.Importantly, however, AVN ablation did not result in additional functional improvement, such as LVEF, NYHA functional class or quality of life.More over, complete atrioventricular block, either spontaneous or induced, did not reduce mortality in a cohort of 155 CRT patients with permanent atrial fibrillation.The effect of CRT-P implantation and AVN-Ablation in patients with therapy refractory, symptomatic atrial fibrillation with LVEF > 35% and narrow QRS complex remains unclear.In this study, we evaluated the benefit of CRT-P implantation and consecutive AVN ablation in these patients in a real-world setting.
We report a case of a pacemaker generator of an epicardial system migrated into the abdominal cavity due to a traffic accident and its subsequent retrieval with a laparoscopic technique in an adult patient.The retrieval of the dislocated pacemaker proceeded without any incident.The pacemaker generator was placed in a parasternal subpectoral pocket on the left chest wall, which makes another perforation highly impossible.
Background: Sclerosis of the sinus of valsalva correlates with cardiovascular disease burden.The anatomic proximity of the aortic root to the conduction system suggests potential association between sinus of valsalva sclerosis and conduction abnormalities.Methods: ECGs and clinical records from 129 consecutive patients undergoing transesophageal echocardiography for routine stroke work-up were collected from a single centre database.TEE standard loops and stand-ard 12 lead ECG recordings were analysed by 3 experienced cardiologists.Results: Of 129 patients, sclerosis of the sinus of valsalva was detected in 72 (55.8%), 39 (30.2%) had aortic valve sclerosis and 67 (51.9%) showed plaques of at least grade I in the ascending aorta.Conduction abnormalities and arrhythmias were found in 63 patients amongst others 30 with grade I, or higher AV-block, 10 patients with sinus node dysfunction, and 20 with atrial fibrillation.Sclerosis of the sinus of valsalva occurred in 42 of these 63 patients (p=0.022).Of 30 patients with AV-block grade I or higher, 26 presented a sinus valsalva sclerosis (p<0.001),7 of 10 patients with sinus node dysfunction presented a sinus valsalva sclerosis (p=0.508) and 15 of 20 with atrial fibrillation (p=0.081). Conclusion:Sclerosis of the sinus of valsalva is associated with atrioventricular conduction abnormalities.atrioventricular sinus area who underwent aortic valve replacement surgery are significantly more likely to need temporary cardiac pacing than those without annular calcification [8].We analysed TEE loops and standard 12-lead ECGs of 129 consecutive patients, undergoing cardiologic work-up after TIA/ stroke, for sclerosis of the sinus of Valsalva and the presence of conduction abnormalities such as atrioventricular blockage (AVB), right bundle branch blockage (RBB), left bundle branch blockage (LBB) and sinus node disease (SND). Materials and Methods Patient population and patient baseline characteristicsWe retrospectively analysed TEE studies and standard 12-lead ECGs of 129 consecutive patients at the Cardiology division of a tertiary care regional hospital in the greater Zurich area.Patient records were analysed for demographics, co-morbidities at or before the examination date, cardiovascular risk factors, and cardiovasculardrug therapy.Patients undergoing TEE for endocarditis evaluation or with congenital heart disease were excluded.The cantonal ethics committee of Zurich acknowledged retrospective data analysis for research purposes (KEK-ZH-Nr.2014-0529).To characterize the study population and to identify a potential correlation between arrhythmias and sinus valsalva sclerosis, the following parameters were tabled as baseline characteristics: Age, BMI, heart disease divided in coronary heart disease (1-, 2-or 3-vessel), dilated cardiomyopathy and valvular cardiomyopathy, dyslipidaemia, smoking, type II diabetes mellitus, hypertension, history of ST-elevation myocardial infarction, cerebrovascular insult, transient ischemic attack, peripheral arterial occlusive disease,
Abstract Background: The antioxidant defense system has been subject to investigations in various cardiovascular diseases. The studies of its status in paroxysmal atrial fibrillation are scarce. The enzyme glucose-6-phosphate dehydrogenase is the main source of reducing equivalents and its activity is crucial for the antioxidant defense system of the cell. Purpose: To study the activity of glucose-6-phosphate dehydrogenase in dynamics as an indicator of the antioxidant defense system in patients with paroxysmal atrial fibrillation (<48 hours). Patients and methods: The enzyme was studied in erythrocytes of 51 patients (59.84±1.60, 26 males) immediately after hospitalization, 24 hours and 28 days after sinus rhythm restoration. It included also 52 healthy controls (59.50±1.46, 26 males), matching the patients by gender and age. The rhythm regulation was achieved by propafenone . The enzyme activity was determined spectrophotometrically. Results : The mean duration of atrial fibrillation episodes prior to hospitalization was 8.1 hours, the majority of the patients being hospitalized on the 5
Multiple coronary artery aneurysms (CAA) with a giant CAA are rare. Patient with a giant CAA is at risk of thrombosis, aneurysm rupture and even sudden cardiac death. We reported a case of a 78-year-old woman having a giant CAA (43 mm × 37 mm) of proximal left anterior descending artery as well as multiple small CAA of both left and right coronary arteries. The spontaneous rupture of the giant CAA combined with previously undiagnosed constrictive pericarditis leaded to severe dyspnea, edema of lower extremities, and syncope. Emergency electrocardiogram (ECG) showed remarkable sinus bradycardia, sinus arrest and atrioventricular junctional rhythm, indicating sick sinus syndrome. Temporary cardiac pacemaker therapy was performed urgently to avoid sudden cardiac death. Multiple non-invasive imaging tests revealed constrictive pericarditis possibly caused by tuberculosis, and giant CAA with the possibility of rupture. Then pericardiotomy and resection of giant aneurysm were performed urgently. Postoperative course was uneventful. The patient became asymptomatic and was discharged in good health. To the best of our knowledge, this is the first case of spontaneous rupture of giant CAA in a patient with constrictive pericarditis, with a rare complication of sick sinus syndrome.
Background: Recent research has demonstrated disturbances of copper balance in the development of cardiovascular diseases.Copper status in patients with atrial fibrillation is still unknown.Serum or plasma copper and ceruloplasmin activity are widely used laboratory indicators of copper status.Purpose: То evaluate copper status in the early hours of paroxysmal atrial fibrillation and monitor its changes after sinus rhythm restoration.Methods: Serum copper levels and plasma oxidase activity of ceruloplasmin were measured in 33 patients with paroxysmal atrial fibrillation (17 males, 16 females, mean age 60.03±1.93).Indicators were measured upon hospital admission, on the 24 th hour and on the 28 th day after sinus rhythm restoration.Thirty-three control subjects were also enrolled in the study (17 males, 16 females, mean age 59.27±1.72)and their indicators were measured only once.Copper levels and ceruloplasmin activity were quantified by atomic absorption spectrometry and colorimetric enzymatic assay respectively.Results: Mean duration of atrial fibrillation episodes up to hospitalization was 8.64±1.03hours (from 2 hours up to 24 hours).Upon admission, patients' copper levels and ceruloplasmin activity were decreased compared to controls (16.77±0.59 vs. 18.30±0.45µmol/L, p<0.05; 0.03±0.01 vs. 0.07±0.01A 530 /mg protein, p<0.001 respectively).24 hours after rhythm conversion, copper was not substantially different (17.11±0.71 vs. 18.30±0.45µmol/L, p>0.05), whereas ceruloplasmin activity was diminished (0.05±0.01 vs. 0.07±0.01A 530 /mg protein, p<0.001).On 28th day we established significant difference in neither of the indicators (17.61±0.48 vs. 18.30±0.45µmol/L, p>0.05; 0.06±0.01 vs. 0.07±0.01A 530 /mg protein, p>0.05). Conclusion:Our results provide evidence for disturbances of copper homeostasis in patients with paroxysmal atrial fibrillation.Decreased copper levels and ceruloplasmin activity during the first hours of arrhythmia and their subsequent elevation following sinus rhythm restoration give us grounds to assume that these changes are closely related to the disease pathogenesis.independent risk factor for cardiovascular incidence and mortality [11,12].Despite the keen clinical and research interest in copper, searching in Science Direct, Scopus, PubMed and Google Scholar database done until February 2014 found single studies on copper status in patients with atrial fibrillation (AF), with ambiguous results presented [13,14].No data were found about the copper status of such patients after sinus rhythm restoration, which would give additional grounds to seek relation with the pathogenetic mechanisms of the disease.
Post-mortem studies on the relationship between coronary artery lesions and cigarette smoking in smoker subjects who died from AMI are numerically of scarce consistency if compared to the epidemiological and clinical findings.However, autopsy examination provides certain results on the definition of the existing link.This study, which analyzed 80 autopsy cases of smokers (n° 68) and non-smokers (n° 12) as a control group who died from AMI, showed that coronary arteries of smokers displayed more severe narrowing partially or totally occluding vessel lumen because of a superimposed thrombus and a higher incidence of three vessel coronary disease with a statistically significant difference.Calcium deposits in the coronary wall were also seen.However, the type and morphology of the alterations in both groups were similar to that observed in the lesions that usually can be documented in the histologic specimens of patients who died from AMI, any cause determined. Materials and Methods80 subjects, 62 men (77.5%) and 18 females (22.5%) aged from 48 to 78 years (mean: 65.8+/-13.4years) died from AMI and underwent the post-mortem study.Sixty-eight subjects (85%) were smokers, while 12 non-smokers (15%) were as a control group.Table 1 summarizes the main characteristics of the study population.Post-mortem examination of the heart and coronary vessels was carried out by using a method previously described [18-21] (Figures 1 and2).In each patient, the heart was removed severing the pulmonary artery and aorta about 5 cm above the free margin of the semilunar valves.After observing and recording the external aspect of the heart to identify macroscopically the areas of myocardial lesions, without cutting the heart and coronary vessels, a rubber was placed through the aorta into the aortic orifice to impede the flux of liquid material to the left ventricular cavity and, then, the coronary arteries were injected at a pressure of 130 mmHg using a barium-iodine-gelatin radiopaque mass by a canoe tied into the aorta (Figure 1).When a good degree of contrast was observed by means of x-rays, all the hearts were fixed in 10% water-formalin solution.Then, five to six transverse slices of thickness approximately 1 cm were cut from the apex to the base (Figure 2).These slices were parallel to each other and atrioventricular sulcus.The thickness of the ventricular wall of each slice was measured and its mean mathematically measured.In addition, the location, size, and age of myocardial alterations,
Introduction:The optimal treatment strategy for left main coronary artery disease continues to be debated.This is particularly evident for the high risk subgroup of patients presenting with acute coronary syndrome (ACS) and who are underrepresented in published trials.The electrocardiogram (ECG) represents one of the first line diagnostic tests for evaluating patients with possible ACS.Specific acute ECG abnormalities can raise the suspicion of significant left main (LM) involvement.Our aim, therefore, was to analyze the ECG patterns of ACS patients undergoing percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) lesions. Methods:Between February 2004 and December 2012 there were 67 patients with left main coronary stenosis (mean age 70 ± 18 years) who underwent acute PCI.We retrospectively analyzed the patients' electronic charts and obtained data on personal history, medication, clinical status, cardiac biomarkers, electrocardiograms on admission, details of the performed coronary angiography with subsequent PCI and patient outcome.In 25 of the patients the urgent PCI was performed on a protected vessel (post CABG with at least one functional graft to LAD/LCX), and we excluded these patients.Results: Follow-up data was available from 42 patients (100%).The cumulative mortality rate (in hospital and at 6 months) in patients with acute interventions in symptomatic LMCA stenosis was 23.8% (10 patients).The most common ECG patterns were significant ST-segment elevation in lead aVR, significant ST-segment depression in leads V4-V6, and first degree atrioventricular (AV) block. Conclusion:In our analysis the most common ECG patterns in patients with acute coronary syndrome related to left main disease were significant ST-segment elevation in lead aVR, significant STsegment depression in leads V4-V6 and AV block.In this study with a small sample size and limited cases there were no specific ECG patterns on admission that were indicative of an adverse outcome in ACS patients related to an unprotected left main culprit lesion.
