Domains of Physical Activity in Relation to Stiffness Index in the General Population.

Background Regular exercise training represents an important modifier of arterial stiffness (AS). Therefore, sex‐specific relations between domains of physical activity (PA; commuting, domestic, and leisure‐time PA, including active sport and occupational PA) with AS were investigated. Methods and Results Stiffness index by digital photoplethysmography was investigated in 12 650 subjects from the GHS (Gutenberg Health Study). Self‐reported PA was evaluated by the “Short Questionnaire to Assess Health‐Enhancing Physical Activity” and reported as activity score peer week, being a combined measure of duration, frequency, and intensity of PA. Multivariable linear regression analysis demonstrat…

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism.

AbstractAimsCatheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated. We investigated patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort.Methods and resultsData from hospitalizations with PE (International Classification of Disease code I26) between 2005 and 2016 were collected by the Federal Office of Statistics in Germany. Patients with PE who underwent CDT (OPS 8-838.60 or OPS code 8-83b.j) were compared with patients receiving…

The impact of aircraft noise on vascular and cardiac function in relation to noise event number: a randomized trial

Abstract Aims Nighttime aircraft noise exposure has been associated with increased risk of hypertension and myocardial infarction, mechanistically linked to sleep disturbance, stress, and endothelial dysfunction. It is unclear, whether the most widely used metric to determine noise exposure, equivalent continuous sound level (Leq), is an adequate indicator of the cardiovascular impact induced by different noise patterns. Methods and results In a randomized crossover study, we exposed 70 individuals with established cardiovascular disease or increased cardiovascular risk to two aircraft noise scenarios and one control scenario. Polygraphic recordings, echocardiography, and flow-mediated dila…

1-Year Outcomes of Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Stents

Abstract Objectives The purpose of this study was to compare the 1-year outcomes of the ABSORB everolimus-eluting bioresorbable scaffold (BRS) (Abbott Vascular, Santa Clara, California) and the XIENCE everolimus-eluting stent (EES) (Abbott Vascular) in patients undergoing percutaneous coronary intervention. Background Randomized studies of the ABSORB BRS have been performed in selected patient and lesion scenarios. The available registries of the ABSORB BRS reflect real-world practice more closely compared with randomized studies, but most of them are limited by the small sample size and the lack of comparative outcomes versus second-generation drug-eluting stents. Methods A total of 1,189 …

A Negative FFR (Intracoronary Adenosine Bolus)

This case describes the assessment of FFR for a single intermediate stenosis in the mid LAD. Since the procedure was performed using a radial access, and given the history of asthma, we preferred to use intracoronary adenosine as the vasodilator of choice. A first bolus of 50 μg was given, followed by a second one of 140 μg. The FFR was reproducible at 0.93, demonstrating that the stenosis was not relevant from the hemodynamic perspective.

The Impact of Venous Pressure on FFR: Do Diuretics Affect FFR?

Central venous pressure influences FFR measurements because it decreases the perfusion gradient distal to the stenosis proportionally more than it does proximal to it. The impact of central venous pressure is minimal for normal pressure values and for FFR values away from the threshold. However, in conditions where FFR is close to 0.80 and central venous pressure is high, it might play an important role in reclassifying stenoses from not relevant to relevant.

FFR in a Bypass

FFR can be used to determine whether by-pass lesions are significant. In this case, an additional complication was the fact that the lesion was placed at the ostium of the graft: in this case, it is important to retract the guiding catheter to avoid wedging.

The pleiotropic effects of antiplatelet therapies

Percutaneous coronary intervention is the most often used method for coronary revascularization. Stenting restores blood perfusion to ischemic areas, but it also causes mechanical disruption of the atheromatous plaque and the nearby endothelium, stimulating the activation of platelets. In a similar way, platelets are activated by thrombin exposure in the setting of plaque rupture. The interaction between platelets, oxidative stress and inflammation is an important factor determining the extent and severity of vascular dysfunction observed in these settings. Platelets activated by the vessel trauma release inflammatory and mitogenic mediators into the vascular microenvironment, activating le…

Impact of atrial fibrillation on in-hospital mortality of ischemic stroke patients and identification of promoting factors of atrial thrombi – Results from the German nationwide inpatient sample and a single-center retrospective cohort

Abstract Ischemic stroke is one of the leading causes of death and disability. Atrial fibrillation (AF) is a well-recognized risk factor for ischemic stroke. We aimed to investigate the impact of AF on in-hospital mortality of ischemic stroke patients and to identify parameters associated with intra-cardiac thrombogenic material. Patients were selected by screening the nationwide sample for ischemic stroke by ICD-Code (I63), stratified for AF. In this cohort, the association between in-hospital deaths and AF was investigated. In a second study, we performed a retrospective analysis of patients who underwent transesophageal echocardiography (TEE) for various reasons, assigned these to 2 grou…

A Complex Combination of Microvascular and Macrovascular Diseases

When FFR is larger than 0.80, a PCI is not justified. Transient microvascular dysfunction may, however, be associated with impaired hyperemia and falsely negative FFR. This case also emphasizes the dynamic nature of microvascular disease, and provides an example of both “typical” syndrome X and “less conventional” syndrome slow flow associated with increased peripheral resistances (see Chap. 35).

Evidence of impaired coronary flow reserve and elevated microvascular resistances in a case of recurrent left apical ballooning.

A 56-year old man was admitted for precordial pain associated with dyspnea and evidence of myocardial ischemia on ECG and cardiac ultrasound. His previous history included an episode of left apical ballooning five years before. At angiography, no evidence of significant epicardial coronary artery disease was manifest. Interestingly, both coronary flow reserve and the index of microvascular resistances were abnormal, showing evidence of impaired microvascular function. This is the first report providing direct evidence of microvascular dysfunction in a patient with (recurrent) apical ballooning.

Bioresorbable vascular scaffold use for coronary bifurcation lesions: A substudy from GHOST EU registry

Objectives The aim of this study was to evaluate midterm outcomes of bioresorbable vascular scaffolds (BVS) implanted in bifurcation lesions. Background BVS have emerged as an alternative to conventional metallic drug-eluting stents for the treatment of coronary complex lesions. Methods Between November 2011 and January 2014, 1189 patients underwent percutaneous coronary intervention with BVS at 10 European centers (GHOST EU registry). Of these, 289 consecutive patients (302 bifurcation lesions) treated with either single-stenting (n = 260) or double-stenting (n = 42) were evaluated. Results True bifurcations were treated in 44.7%. Intravascular ultrasound and optical coherence tomography w…

Association of transcatheter direct mitral annuloplasty with acute anatomic, haemodynamic, and clinical outcomes in severe mitral valve regurgitation.

Abstract Aims Several approaches for transcatheter mitral valve repair for functional mitral valve regurgitation are established. Interventional direct annuloplasty is a novel trans‐venous, trans‐septal approach. While feasibility was proven recently, knowledge on its influence on cardiac dimensions, pressures, biomarkers, and clinical outcomes is sparse. Methods and results Patients consecutively treated with direct annuloplasty‐only procedures between December 2015 and April 2018 were included in this monocentric analysis. Echocardiographic measurements, biomarker levels, clinical status [New York Heart Association (NYHA) class and 6 min walk test] were assessed at baseline, at discharge,…

Coronary venous therapy to improve microvascular dysfunction.

The coronary circulation is a complex system in which vascular resistances are determined by an interplay of forces in at least three compartments: the epicardial, the microvascular, and the venous district. Cardiologists, and particularly interventional cardiologists, normallly place the focus of their attention on diseases of the epicardial coronary circulation as possible causes of coronary syndromes and neglect the importance of the other two compartments of coronary circulation. The study of the coronary microcirculation, an increasingly recognized source of ischemia, has long been disregarded, but is witnessing a revival since the (re-)introduction of diagnostic tools in the better eq…

Coronary Stent Strut Fractures: Classification, Prevalence and Clinical Associations

Introduction. The frequency, characteristics and clinical implications of Strut fractures (SFs) remain incompletely understood. Methods and results. A total of 185 (160 patients) newer-generation drug-eluting stents (DES) were imaged. SFs were found in 21 DES (11.4%) and were classified in four patterns: one single stacked strut (41%)

Predilation, sizing and post-dilation scoring in patients undergoing everolimus-eluting bioresorbable scaffold implantation for prediction of cardiac adverse events: Development and internal validation of the PSP score

Aims: The aim of the study was to develop a scoring model to evaluate the quality of bioresorbable vascular scaffold (BVS) implantation and determine the model's usefulness in predicting adverse cardiac events. Methods and results: The implantation technique and clinical outcomes of 1,736 lesions treated with BVS were analysed using the GHOST-EU registry. Predilation, scaffold sizing, and post-dilation (PSP) were scored according to the hazard model derived from the weight of these variables. The primary end-point was a one-year device-oriented composite endpoint (DoCE) composed of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularisation. Def…

Predictors of early scaffold thrombosis: results from the multicenter prospective German-Austrian ABSORB RegIstRy.

BACKGROUND In randomized clinical trials, the risk of thrombotic events with the absorb bioresorbable vascular scaffold (BVS) was significantly higher than with metallic drug-eluting stents. We evaluated predictors of scaffold thrombosis in the large-scale, multicenter German-Austrian ABSORB RegIstRy. METHODS AND RESULTS 3178 patients with treatment of 4252 lesions using 5020 scaffolds were included. Follow-up rate at 6 months was 97.4%. Forty-five (1.42%) patients experienced definite/probable scaffold thrombosis during follow-up. Multiple regression analysis showed implantation of absorb BVS in bifurcation lesions [odds ratio (OR): 4.43; 95% confidence interval (CI): 1.69-11.59; P=0.0024]…

Monitoring White Blood Cell Mitochondrial Aldehyde Dehydrogenase Activity: Implications for Nitrate Therapy in Humans

Recent animal data suggest that reduced lipoic acid (LA) prevents oxidative inhibition of the nitrate bioactivating enzyme, the mitochondrial aldehyde dehydrogenase (ALDH-2), and that pentaerythritol tetranitrate (PETN) does not induce nitrate tolerance because of its intrinsic antioxidative properties, thereby preserving ALDH-2 activity. We sought to determine whether ALDH-2 activity in circulating white blood cells (WBCs) can be used to monitor nitrate tolerance and whether LA can prevent nitroglycerin tachyphylaxis in humans. Eight healthy male volunteers received, in randomized order, a single dose of glyceryl trinitrate (GTN; 0.8 mg), PETN (80 mg), or GTN plus LA (600 mg) orally. GTN (…

In vitro and in vivo characterization of a new organic nitrate hybrid drug covalently bound to pioglitazone.

<b><i>Background/Aims:</i></b> Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. The new compound CLC-3000 is an aminoethyl nitrate (AEN) derivative of pioglitazone, a thiazolidinedione antidiabetic agent combining the peroxisome proliferator-activated receptor γ agonist activity of pioglitazone with the NO-donating activity of the nitrate moiety. <b><i>Methods:</i></b> In vitro and in vivo characterization was performed by isometric tension recording, platelet function, bleeding time and detection of oxidative stress. <b><i>Results:</i></…

Apple Watch detecting coronary ischaemia during chest pain episodes or an apple a day may keep myocardial infarction away

Rosiglitazone Causes Endothelial Dysfunction in Humans

We explored the impact of rosiglitazone on endothelial function in normal volunteers and its interaction with glyceryl trinitrate (GTN)-induced abnormalities in endothelial function. We hypothesized that rosiglitazone would have a neutral effect on endothelial function in normal volunteers and would favorably modify endothelial dysfunction induced by GTN.In this double-blind, randomized, placebo-controlled study, 44 participants were randomized to placebo, rosiglitazone (4 mg twice daily), transdermal GTN (0.6 mg/h), or both GTN and rosiglitazone. After 7 days of treatment, participants underwent measures of forearm blood flow during brachial artery infusion of acetylcholine (Ach). Serum gl…

ADMA and arginine derivatives in relation to non-invasive vascular function in the general population.

Nitric oxide produced from l-arginine is central to vascular homeostasis. Little is known about the relationship between arginine derivatives including asymmetric dimethylarginine (ADMA) and non-invasive vascular function measures in the general population.In 5000 individuals (median age 56; 25th/75th percentile: 46, 65; 49% women) taking part in the population-based Gutenberg Health Study (Mainz area, Germany), we measured the relationship between the arginine derivatives asymmetric dimethylarginine (ADMA), N-monomethyl l-arginine (NMMA), symmetric dimethylarginine (SDMA) and l-arginine with flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT). Weak bivariate correlations w…

Heart Failure: Really Idiopathic?

Coronary angiography is necessary in the differential diagnosis of a newly discovered heart failure, which may be caused by multivessel disease and/or stenoses of major vessels. However, angiography is associated with a relatively high percentage of false negative findings in the assessment of left main disease. FFR allows unveiling these false negatives, even though special precautions need to be taken when stenoses are present also in the bifurcation branches.

Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads to moderate neovascularization in chronic myocardial ischemia in pigs.

Microcirculation (2010) 17, 69–78. doi: 10.1111/j.1549-8719.2010.00002.x Abstract Background:  This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. Methods and Results:  Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-…

Coronary artery disease: seeing or foreseeing?

This editorial refers to ‘Discordance between Framingham Risk Score and atherosclerotic plaque burden’, by A. Pen et al., doi:10.1093/eurheartj/ehs473 The prevention of cardiovascular disease (CVD) has been a major priority and challenge for policy-makers and healthcare workers for at least five decades. In this ‘co-ordinated set of actions, at public and individual level, aimed at eradicating, eliminating, or minimizing the impact of CVDs and their related disability’,1 the capacity to predict the presence of coronary atherosclerosis obviously plays a central role. Studies show that the combination of a few major risk factors is an easily accessible proxy for risk stratification: the Europ…

Direct quantification of cell-free, circulating DNA from unpurified plasma.

Cell-free DNA (cfDNA) in body tissues or fluids is extensively investigated in clinical medicine and other research fields. In this article we provide a direct quantitative real-time PCR (qPCR) as a sensitive tool for the measurement of cfDNA from plasma without previous DNA extraction, which is known to be accompanied by a reduction of DNA yield. The primer sets were designed to amplify a 90 and 222 bp multi-locus L1PA2 sequence. In the first module, cfDNA concentrations in unpurified plasma were compared to cfDNA concentrations in the eluate and the flow-through of the QIAamp DNA Blood Mini Kit and in the eluate of a phenol-chloroform isoamyl (PCI) based DNA extraction, to elucidate the D…

Nitroglycerin-induced endothelial dysfunction and tolerance involve adverse phosphorylation and S-glutathionylation of endothelial nitric oxide synthase — Beneficial effects of therapy with the AT1-receptor blocker telmisartan

Continuous administration of nitroglycerin (GTN) causes tolerance and endothelial dysfunction by inducing reactive oxygen species (ROS) production from various enzymatic sources, such as mitochondria, NADPH oxidase, and an uncoupled endothelial nitric oxide synthase (eNOS). In the present study, we tested the effects of type 1 angiotensin (AT(1))-receptor blockade with telmisartan on GTN-induced endothelial dysfunction in particular on eNOS phosphorylation and S-glutathionylation sites and the eNOS cofactor synthesizing enzyme GTP-cyclohydrolase I.Wistar rats were treated with telmisartan (2.7 or 8 mg/kg per day PO for 10 days) and with GTN (50 mg/kg per day SC for 3 days). Aortic eNOS phos…

Oxidative stress and endothelial dysfunction: therapeutic implications.

In a previous issue of Annals of Medicine, we presented evidence in support of the concept that an abnormally increased production of reactive oxygen species plays a central role in the genesis and progression of cardiovascular disease. While a number of preclinical lines of evidence support this concept, and despite the results of many studies suggesting a beneficial impact of antioxidant drugs on endothelial function, large clinical trials have failed to demonstrate a benefit of antioxidants on cardiovascular outcomes. Studies exploring the possibility that classical antioxidants such as vitamin C, vitamin E, selenium, or folic acid may improve the prognosis of patients with cardiac disea…

Short‐term e‐cigarette vapor exposure causes vascular oxidative stress and dysfunction ‐ evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX‐2)

Coronary Slow Flow in a Patient with Myocarditis

A young patient presented with dyspnea and high troponin. Coronary angiography excluded a diagnosis of CAD, but was diagnostic for the presence of coronary slow flow. Thermodilution showed increased resting resistances in the presence of hypernormal CFR.

Cardiac biomarkers and arterial stiffening: data from the Gutenberg Health study

Psoriasis and its impact on the clinical outcome of patients with pulmonary embolism

Abstract Background Venous thromboembolism (VTE) is common and associated with high morbidity and mortality. Although chronic inflammation was not categorized as a traditional risk factor for VTE, chronic inflammation might increase the risk to develop VTE events. While studies confirmed an increased cardiovascular morbidity and mortality in psoriatic patients, data regarding the influence of psoriasis on patients' cardiovascular profile and on prognosis of patients with pulmonary embolism (PE) are sparse. Purpose We aimed to investigate the impact of psoriasis on prognosis of PE patients. Methods Hospitalized PE patients were stratified for psoriasis and the impact of psoriasis on outcome …

Serial assessments of microvascular obstruction by contrast-enhanced magnetic resonance predict contractile recovery and clinical outcome after reperfused acute myocardial infarction.

AIMS The purpose of the study was to investigate, using cardiac magnetic resonance (CMR), the presence and time course of microvascular obstruction (MO) in patients with acute myocardial infarction (AMI), and to test its relationship with cardiac remodeling and clinical outcomes. METHODS AND RESULTS 53 patients with AMI and successful percutaneous reperfusion underwent CMR examination at four separate timepoints: within the first 48 hours, at 10 days, at six and twelve months after infarction. MO was quantified immediately (early imaging) and 10 minutes (late imaging) after contrast administration in each session. The extent of MO decreased from early to late imaging at both the first and t…

Invasive treatment of NSTEMI patients in German Chest Pain Units - Evidence for a treatment paradox.

Background: Patients with non ST-segment elevation myocardial infarction (NSTEMI) represent the largest fraction of patients with acute coronary syndrome in German Chest Pain units. Recent evidence on early vs. selective percutaneous coronary intervention (PCI) is ambiguous with respect to effects on mortality, myocardial infarction (MI) and recurrent angina. With the present study we sought to investigate the prognostic impact of PCI and its timing in German Chest Pain Unit (CPU) NSTEMI patients. Methods and results: Data from 1549 patients whose leading diagnosis was NSTEMI were retrieved from the German CPU registry for the interval between 3/2010 and 3/2014. Follow-up was available at m…

5-Year Experience of In-Hospital Outcomes After Percutaneous Left Atrial Appendage Closure in Germany

The aim of this study was to evaluate 5-year in-hospital trends and safety outcomes of left atrial appendage (LAA) closure in the German nationwide inpatient sample.The safety and efficacy of percutaneous LAA closure have been demonstrated in randomized trials and prospective cohort studies, but results from large samples are missing.Data on patient characteristics and in-hospital safety outcomes for all percutaneous LAA closures performed in Germany between 2011 and 2015 were analyzed. Overall, 15,895 inpatients were included.The annual number of LAA occlusions increased from 1,347 in 2011 to 4,932 in 2015 (β = 1.00; 95% confidence interval [CI]: 0.95 to 1.01; p 0.001), with a nonsignifica…

Mismatch Between Imaging and Functional Relevance of Coronary Stenoses: Seeing Is Not Believing

This case emphasizes the differences between structural, anatomic, and functional assessment of coronary lesions. Both the LAD and the RCX presented lesions which, while seemingly severe at optical coherence tomography, did not cause functional obstruction.

Advanced Protocol for Three-Dimensional Transesophageal Echocardiography Guidance Implementing Real-Time Multiplanar Reconstruction for Transcatheter Mitral Valve Repair by Direct Annuloplasty.

Transcatheter direct annuloplasty has been introduced as a novel interventional treatment option for severe mitral valve regurgitation. Until now, only one direct annuloplasty device (Edwards Cardioband) has been commercially available, being implanted in more than 250 patients worldwide. Yet this procedure poses greater challenges regarding optimal fluoroscopic and echocardiographic guidance compared with edge-to-edge repair: correct localization and orientation of the anchors upon penetration into the fibrous mitral annulus tissue and the basal left ventricular myocardium are preconditions for an optimal result and essential to avoid damage of the neighboring structures (atrioventricular …

Multiple Lesions, Multiple Measures

This case describes the assessment of FFR in the case of tandem intermediate lesions in the proximal and mid LAD. Hyperemia was induced with intravenous (IV) infusion of Adenosine, which allows pullback measurements. First, with the wire placed distal in the vessel, FFR provides information on whether the sum of the two stenoses causes ischemia. Thereafter, during pullback, the most severe stenosis can be identified as the most relevant pressure drop. Finally, a re-evaluation of FFR is important after PCI: after the first stenosis is treated, the degree of hyperemia achievable will be larger, thus unmasking the relevance of the second one.

Non-Hemodynamic Effects of Organic Nitrates and the Distinctive Characteristics of Pentaerithrityl Tetranitrate

Organic nitrates are among the oldest and yet most commonly employed drugs in the long-term therapy of coronary artery disease and congestive heart failure. While they have long been used in clinical practice, our understanding of their mechanism of action and side effects remains incomplete. For instance, recent findings provide evidence of previously unanticipated, non-hemodynamic properties that include potentially beneficial mechanisms (such as the induction of a protective phenotype that mimics ischemic preconditioning), but also toxic effects (such as endothelial and autonomic dysfunction, rebound angina, tolerance). To date, the most commonly employed organic nitrates are isosorbide …

Starting Easy: FFR in a High-Grade Stenosis

A simple representative case of FFR in a high-grade stenosis. The gradient is confirmed by pushing the sensor forward. Equalization is confirmed at the end of the procedure.

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism

Abstract Background and purpose Catheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated or has failed. We investigated baseline characteristics and in-hospital outcomes of patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort. Methods Data from hospitalizations with PE between 2005 and 2016 were collected by the Federal Office of Statistics (Statistisches Bundesamt) in Germany and included in this analysis. Patients with PE who unde…

Impaired Fractional and Coronary Flow Reserve

A FFR <0.80/0.75 witnesses the existence of a high-grade epicardial stenosis. In this setting, the CFR is usually also impaired since even a maximal dilation of the peripheral resistances cannot compensate for the increased epicardial resistances.

TCT-419 Usefulness of a scoring system for predicting adverse cardiovascular events in patients undergoing everolimus-eluting bioresorbable scaffolds implantation: the PSP score

Gene therapy with iNOS enhances regional contractility and reduces delayed contrast enhancement in a model of postischemic congestive heart failure

Aims: The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia. Methods: Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control. Results: The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. Wall thickness at end-…

Is oxidative stress a therapeutic target in cardiovascular disease?

An abnormal production of reactive oxygen species (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide (NO) have long been proposed to be the common pathogenetic mechanism of the endothelial dysfunction, resulting from diverse cardiovascular risk factors such as hypercholesterolaemia, diabetes mellitus, chronic smoking, metabolic syndrome, and hypertension. Superoxide produced by the nicotinamide dinucleotide phosphate (NADPH) oxidase, mitochondrial sources, or the xanthine oxidase may react with NO, thereby resulting in excessive formation of peroxynitrite, a reactive nitrogen species that has been demonstrated to accelerate the atherosclerotic process by causing d…

Observations of time-based measures of flow-mediated dilation of forearm conduit arteries: implications for the accurate assessment of endothelial function

Endothelium-dependent flow-mediated dilation (FMD) is measured as the increase in diameter of a conduit artery in response to reactive hyperemia, assessed either at a fixed time point [usually 60-s post-cuff deflation (FMD60)] or as the maximal dilation during a 5-min continuous, ECG-gated, measurement (FMDmax-cont). Preliminary evidence suggests that the time between reactive hyperemia and peak dilation (time to FMDmax) may provide an additional index of endothelial health. We measured FMDmax-cont, FMD60, and time to FMDmax in 30 young healthy volunteers, 22 healthy middle-aged adults, 16 smokers, 23 patients with hypertension, 40 patients with coronary artery disease, and 22 patients wit…

Pentaerithrityl tetranitrate improves angiotensin II induced vascular dysfunction via induction of heme oxygenase-1

The organic nitrate pentaerythritol tetranitrate is devoid of nitrate tolerance, which has been attributed to the induction of the antioxidant enzyme heme oxygenase (HO)-1. With the present study, we tested whether chronic treatment with pentaerythritol tetranitrate can improve angiotensin II–induced vascular oxidative stress and dysfunction. In contrast to isosorbide-5 mononitrate (75 mg/kg per day for 7 days), treatment with pentaerythritol tetranitrate (15 mg/kg per day for 7 days) improved the impaired endothelial and smooth muscle function and normalized vascular and cardiac reactive oxygen species production (mitochondria, NADPH oxidase activity, and uncoupled endothelial NO synthase)…

Airborne disease: a case of a Takotsubo cardiomyopathie as a consequence of nighttime aircraft noise exposure.

Chronic noise exposure (in particular nighttime noise) leads to disturbances of activities, sleep, and communication. As a consequence, emotional responses or annoyance will lead to stress reactions characterized by an activation of the sympathetic nervous system and/or increased levels of circulating stress hormones. We report here a case of a patient, who was exposed to heavy …

Nitrate therapy: new aspects concerning molecular action and tolerance.

Although the short-term vasodilatory properties of organic nitrates are potent and well known, a number of vascular and extravascular changes have been shown to compromise their hemodynamic effects on long-term administration. Among these changes, systemic phenomena such as neurohormonal activation and intravascular volume expansion1 as well as specific vascular changes such as increased vascular superoxide (O2·−) production,2 increased sensitivity to vasoconstrictors,3 and decreased responsiveness to nitric oxide (NO) donors4,5 have long been identified as playing a role. Several hypotheses have been proposed to explain these abnormalities, and over the last 15 years, our groups have focus…

Early outcome after implantation of Absorb bioresorbable drug-eluting scaffolds in patients with acute coronary syndromes

The safety of BVS implantation in patients with a high risk for early thrombotic complications has not been studied. We report on the outcomes of patients with acute coronary syndromes (ACS) treated with bioresorbable, everolimus-eluting, vascular scaffolds (BVS).150 consecutive patients with ACS (194 lesions) treated with BVS between May 2012 and July 2013 were compared with a control group composed of 103 consecutive patients (129 lesions) who underwent everolimus drug-eluting stent (DES) implantation in the same time period. The incidence of major adverse cardiac events (MACE: death, non-fatal myocardial infarction, or reintervention) before discharge, at one month and six months was eva…

Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study

Abstract Aims In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the cl…

Effect of nighttime aircraft noise exposure on endothelial function and stress hormone release in healthy adults.

Aims Aircraft noise disturbs sleep, and long-term exposure has been shown to be associated with increases in the prevalence of hypertension and an overall increased risk for myocardial infarction. The exact mechanisms responsible for these cardiovascular effects remain unclear. Methods and results We performed a blinded field study in 75 healthy volunteers (mean age 26 years), who were exposed at home, in random order, to one control pattern (no noise) and two different noise scenarios [30 or 60 aircraft noise events per night with an average maximum sound pressure level (SPL) of 60 dB(A)] for one night each. We performed polygraphy during each study night. Noise caused a worsening in sleep…

The evolution of the meaning of blood hyperviscosity in cardiovascular physiopathology: Should we reinterpret Poiseuille?

In the 1960s and 1970s, a number of researchers (including ourselves) involved in the study of cardiovascular pathophysiology and particularly in the development of techniques to quantify blood flow, came across the observation that, along with vessel diameter, also blood viscosity plays an important role not only in theory but also in practice. Until then, viscosity was thought to play only a marginal role in determining blood flow, a concept which was based on the 1828 theories of Jean Louis Marie Poiseuille (Fig. 1, and [1]).1 In his well-known formula, named after its fathers Hagen2 and Poiseuille,

A Normal Fractional and Coronary Flow Reserve

Fractional flow reserve (FFR) and coronary flow reserve (CFR) provide different and complementary information on vascular physiology. The two tests provide information, respectively, on the epicardial and total vascular resistances. Typically, a FFR <0.75 is also associated with an impaired CFR (<2); exceptions, however, exist.

Another Easy one: This Time in the Other Direction

A simple representative case of FFR in a focal stenosis which, however, does not induce an FFR blunting below 0.80. The existence of a gradient is confirmed at pullback.

Continuous therapy with transdermal nitroglycerin does not affect biomarkers of vascular inflammation and injury in healthy volunteers.

Continuous exposure to nitroglycerin (GTN) results in development of tolerance and is associated with increased free radical production and abnormal endothelial function. Elevated plasma biomarkers of inflammation have been shown to be associated with endothelial dysfunction in most cardiovascular conditions. It remains unclear whether exposure to GTN is also associated with increased biomarkers of endothelial and vascular injury or vascular inflammation. In an investigator-blind study, a total of 28 healthy volunteers were randomized to continuous therapy with GTN (0.6 mg/h 24 h/day for 7 days) or no therapy. Venous blood was collected on day 0 and day 7. Plasma levels of markers such as …

Abstract 13812: Pulmonary Function Predicts Cardiac Function, Structure &amp; Clinical Outcome in Chronic Heart Failure: Results From the Myovasc Study

Introduction: A growing body of evidence suggests a relevance of pulmonary function in the pathophysiology of heart failure (HF). Comprehensive data on the role of forced expiratory volume in 1 second (FEV1) in the development &amp; progression of HF is limited. Hypothesis: Given this background, we hypothesized, that (FEV1) is associated with deteriorated left ventricular (LV) functional as well as structural status, &amp; predicts specific clinical outcome in HF. Methods: Data from the MyoVasc Study (n=3,289) were analysed. Comprehensive clinical phenotyping including body plethysmography for the evaluation of FEV1 &amp; standardized echocardiography were performed during a five-hour inv…

Impact of diabetes mellitus on mortality rates and outcomes in myocardial infarction

Diabetes mellitus (DM) represents a major cardiovascular risk factor for increased risk of coronary artery disease and myocardial infarction (MI). DM is also associated with a poorer clinical outcome in MI.The nationwide German inpatient population treated between 2005 and 2016 was used for statistical analyses. Hospitalized MI patients were stratified by the presence of DM and investigated for the impact of DM on in-hospital events.In total, 3,307,703 hospitalizations for acute MI (37.6% female patients, 56.8% aged ≥ 70 years) treated in Germany during 2005-2016 were included in this analysis. Of these patients, 410,737 (12.4%) died while in hospital. Overall, 1,007,326 (30.5%) MI cases we…

TNF-α blockade may lead to improvement of vascular function in psoriasis patients.

Psoriasis is one of the most common chronic inflammatory skin diseases and at the same time a risk factor for cardiovascular disease. Interleukin-17A (IL-17A)-mediated inflammation in psoriasis may lead to vascular dysfunction. This study aimed at investigating whether anti-inflammatory treatment by tumor necrosis factor (TNF)-α blockade alters vascular function in psoriasis patients. A total of 11 patients with psoriasis who underwent treatment with either adalimumab (n = 8) or etanercept (n = 3), 10 healthy control individuals and 14 patients with coronary artery disease (CAD) were included in this study. Treatment response was assessed using the Psoriasis Area and Severity Index (PASI) s…

Non-invasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population

AIMS Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of noninvasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality. METHODS AND RESULTS In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N = 12,599) and fingertip peripheral arterial tonometry (N = 11,125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased e…

Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study

Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent mechanism. Whether the chronic administration of HMG-CoA reductase inhibitors provides similar protection remains controversial and is unknown in humans. Eighteen male volunteers were randomized to receive a single dose of rosuvastatin (20 mg) or placebo. Twenty-four hours later, endothelium-dependent, radial artery flow-mediated dilation (FMD) w…

Inorganic Nitrate Therapy Improves Doxorubicin-Induced Cardiomyopathy

The anthracycline doxorubicin (DOX) is a potent and effective antineoplastic antibiotic agent widely used in the treatment of a broad range of forms of cancer. The clinical use of DOX is limited by cardiotoxicity, which increases dose dependently and may lead to dilated cardiomyopathy and clinical

Endothelial function testing and cardiovascular disease: focus on peripheral arterial tonometry

During recent decades, a number of methods have been developed to assess endothelial function, contributing to a better understanding of the pathophysiology of cardiovascular disease. Recently, the advent of noninvasive, reproducible techniques for assessment of endothelial function has opened novel possibilities of application in the clinical setting. Peripheral arterial tonometry is a relatively novel, user-friendly technique measuring finger pulse volume amplitude changes induced by reactive hyperemia following 5 minutes of ischemia in the upper limb. Current evidence indicates that this technique has the potential to significantly impact the field of cardiovascular research and preventi…

Chronic Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction, Oxidative Stress and a Marked Increase in Vascular Endothelin-1 Expression

Aims Isosorbide-5-mononitrate (ISMN) is one of the most frequently used compounds in the treatment of coronary artery disease predominantly in the USA. However, ISMN was reported to induce endothelial dysfunction, which was corrected by vitamin C pointing to a crucial role of reactive oxygen species (ROS) in causing this phenomenon. We sought to elucidate the mechanism how ISMN causes endothelial dysfunction and oxidative stress in vascular tissue. Methods and results Male Wistar rats ( n = 69 in total) were treated with ISMN (75 mg/kg/day) or placebo for 7 days. Endothelin (ET) expression was determined by immunohistochemistry in aortic sections. Isosorbide-5-mononitrate infusion caused si…

Vascular Dysfunction in Experimental Diabetes Is Improved by Pentaerithrityl Tetranitrate but Not Isosorbide-5-Mononitrate Therapy

OBJECTIVE Diabetes is associated with vascular oxidative stress, activation of NADPH oxidase, and uncoupling of nitric oxide (NO) synthase (endothelial NO synthase [eNOS]). Pentaerithrityl tetranitrate (PETN) is an organic nitrate with potent antioxidant properties via induction of heme oxygenase-1 (HO-1). We tested whether treatment with PETN improves vascular dysfunction in the setting of experimental diabetes. RESEARCH DESIGN AND METHODS After induction of hyperglycemia by streptozotocin (STZ) injection (60 mg/kg i.v.), PETN (15 mg/kg/day p.o.) or isosorbide-5-mononitrate (ISMN; 75 mg/kg/day p.o.) was fed to Wistar rats for 7 weeks. Oxidative stress was assessed by optical methods and o…

Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome : a randomised, prospective, controlled study

Introduction Particularly in the setting of acute coronary syndromes, the interplay between vascular and platelet function has been postulated to have direct clinical implications. The present trial is designed to test the effect of clopidogrel, prasugrel and ticagrelor on multiple parameters of vascular function, platelet aggregation, oxidative and inflammatory stress before and up to 4 weeks after coronary artery stenting. Methods and analysis The study is designed as a three-arm, parallel design, randomised, investigator-blinded study. Patients with unstable angina or non-ST elevation myocardial infarction undergoing coronary intervention with a drug-eluting stent will be randomised to r…

Supervised exercise training in peripheral arterial disease increases vascular shear stress and profunda femoral artery diameter

Background Arteriogenesis is promoted by flow- and pressure-related forces such as tangential wall stress and laminar shear stress. Exercise training (ET) is known to promote arteriogenesis in peripheral arterial disease (PAD) patients. It remains unclear whether supervised ET (SET) promotes arteriogenesis more efficiently than non-SET (nSET). Methods and results Forty PAD patients participated in a SET or nSET training programme ( n = 20 each) and were compared to 20 healthy individuals without any history of cardiovascular events. Femoral artery diameter, flow and velocity were measured by ultrasound. Tangential wall stress and laminar shear stress were calculated for femoral arteries. Fo…

Comparison of direct and indirect antioxidant effects of linagliptin with other gliptins — Evidence for antioxidant and antiinflammatory properties of linagliptin

FEV1 Predicts Cardiac Status and Outcome in Chronic Heart Failure

Background COPD is an established predictor of clinical outcome in patients with chronic heart failure (HF). However, little evidence is available about the predictive value of FEV1 in chronic HF. Research Question Is pulmonary function related to the progression of chronic HF? Study Design and Methods The MyoVasc study ( ClinicalTrials.gov Identifier: NCT04064450) is a prospective cohort study of HF. Information on pulmonary and cardiac functional and structural status was obtained by body plethysmography and echocardiography. The primary study end point was worsening of HF. Results Overall 2,998 participants (age range, 35-84 years) with available FEV1 data were eligible for analysis. Lin…

Twelve-month outcomes after bioresorbable vascular scaffold implantation in patients with acute coronary syndromes. Data from the European Multicenter GHOST-EU Extended Registry.

The aim of this study was to report on the midterm outcomes of patients undergoing percutaneous coronary intervention with bioresorbable vascular scaffolds (BVS) for the treatment of acute coronary syndromes (ACS) and compare with those of patients with stable coronary artery disease (sCAD).One thousand four hundred and seventy-seven (1,477) patients underwent implantation of one or more BVS (Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) at 11 European centres and were included in the GHOST-EU registry. Admissions comprised 47.1% of the patients (951 BVS) with ACS, and 52.8% (1,274 BVS) with sCAD. During a median follow-up of 384 (359-460) days, patient-oriented endpoints (PoCE), inclu…

Coronary Stent Thrombosis — Predictors and Prevention

BACKGROUND: Stent thrombosis (ST) is a dreaded complication after stent implantation and is associated with a mortality between 5% and 45%. The mechanisms by which ST arises are complex. Because of the seriousness of this situation, all physicians should have at least basic knowledge of it. In this article, we present the risk factors for ST and discuss some innovative approaches to its treatment. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed, and on current international guidelines and expert recommendations. RESULTS: The frequency of ST has been markedly lowered by technical advances in coronary stenting and by the implementation of modern i…

Impact of overlapping on 1-year clinical outcomes in patients undergoing everolimus-eluting bioresorbable scaffolds implantation in routine clinical practice: Insights from the European multicenter GHOST-EU registry

Background Overlapping implantation of bioresorbable scaffolds (BRSs) are frequent in long coronary lesions. Its impact on clinical outcomes is unknown. Objective: To compare the clinical outcomes of patients treated with overlapping BRS with those patients treated with no-overlap BRS. Methods: We analyzed the 1-year clinical outcomes of 1,477 patients treated with BRS in the GHOST-EU registry, according to the implantation of overlapping BRS. Primary endpoint was patient oriented composite endpoint (PoCE) of: all-cause death, any myocardial infarction (MI) and any repeated revascularization. Scaffold thrombosis, according to Academic Research Consortium definition, was also analyzed. Resul…

Nitroglycerin-Induced Endothelial Dysfunction and Tolerance Involve Adverse Phosphorylation and S -Glutathionylation of Endothelial Nitric Oxide Synthase

Objective— Continuous administration of nitroglycerin (GTN) causes tolerance and endothelial dysfunction by inducing reactive oxygen species (ROS) production from various enzymatic sources, such as mitochondria, NADPH oxidase, and an uncoupled endothelial nitric oxide synthase (eNOS). In the present study, we tested the effects of type 1 angiotensin (AT 1 )-receptor blockade with telmisartan on GTN-induced endothelial dysfunction in particular on eNOS phosphorylation and S -glutathionylation sites and the eNOS cofactor synthesizing enzyme GTP–cyclohydrolase I. Methods and Results— Wistar rats were treated with telmisartan (2.7 or 8 mg/kg per day PO for 10 days) and with GTN (50 mg/kg per d…

A Bifurcation with Surprise

FFR was assessed after provisional stenting of a bifurcation stenosis in the proximal LAD in a very young patient. Pull-back demonstrated a good outcome after PCI, and it revealed the existence of an additional stenosis which, due to its very proximal location in the LAD, could not be seen at angiography. This case emphasizes the importance of performing FFR measurements during sustained hyperemia and using a slow pull-back technique.

Coadministration of atorvastatin prevents nitroglycerin-induced endothelial dysfunction and nitrate tolerance in healthy humans.

Objectives We aimed to assess whether concurrent administration of atorvastatin would modify the development of tolerance and endothelial dysfunction associated with sustained nitroglycerin (GTN) therapy in humans. Background Animal studies have demonstrated that administration of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors can protect against GTN-induced endothelial dysfunction and tolerance, likely through an antioxidant mechanism. Methods Thirty-six healthy male volunteers were randomized to receive continuous transdermal GTN (0.6 mg/h) and placebo, atorvastatin (80 mg/day) alone, or continuous transdermal GTN (0.6 mg/h) with concurrent atorvastatin (80 mg/day), all for 7 …

Sex-Specific Relationship Between Parathyroid Hormone and Platelet Indices in Phenotypes of Heart Failure—Results From the MyoVasc Study

Background: Heart failure (HF) is a multifactorial syndrome with pathophysiological complexities still not fully understood. Higher mean platelet volume (MPV), a potential marker of platelet activation, and high concentrations of parathyroid hormone (PTH) have been implicated in the pathogenesis of HF.Aim: This study aims to investigate sex-specifically the association between PTH concentrations and platelet indices in phenotypes of HF.Methods and Results: PTH and platelet indices (MPV and platelet count) were available in 1,896 participants from the MyoVasc study in Mainz, Germany. Multivariable linear regression models, adjusted for age, sex, season, vitamin D status, cardiovascular risk …

No difference in 30-day outcome and quality of life in transradial versus transfemoral access – results from the German Austrian ABSORB registry (GABI-R)

Abstract Background Radial (RA) instead of femoral access (FA) for coronary interventions has become a European Society of Cardiology Class-IA guideline recommendation. But when the decision on the access site is left to the discretion of the operator, differences in adverse event rates mitigate. Methods We compared the 30-day outcome for RA and FA in all patients recruited for the observational German Austrian ABSORB Registry (GABI-R) in regard to all-cause mortality, stroke, myocardial infarction (MI), TIMI major bleedings (TMB) and quality of life (QoL). All patients were treated with a bioresorbable vascular scaffold. Access site was left to the discretion of the operator. Results In to…

The Assessment of Diffuse Disease

A significant drop in pressure can be observed also in the absence of focal lesions. The presence of hemodynamically relevant, diffuse atherosclerosis is actually very frequent and it may affect as many as 50 % of those patients who have at least one focal lesion in another vessel. FFR in this setting may clarify the possible reason for residual angina after successful stenting.

Mechanismen und klinischer Stellenwert der Nitrattoleranz. Diversität und Nebenwirkungen organischer Nitrate

Die wichtigste Beobachtung der letzten Jahre war, dass es sich bei den organischen Nitraten uberraschenderweise um eine heterogene Gruppe von Vasodilatantien handelt, denen gemeinsam ist, dass sie die losliche GC und die cGMP-abhangige Kinase aktivieren konnen. Alle klinisch wichtigen organischen Nitrate (GTN, ISDN und ISMN) auser dem PETN induzieren eine Toleranzentwicklung und eine endotheliale Dysfunktion bei chronischer Gabe. Aktuelle Arbeiten konnten insbesondere nach Gabe von GTN einen neuen Toleranz-Mechanismen identifizieren, der aus der Hemmung des Nitrat-bioaktivierenden Enzyms, der mitochondrialen Aldehyddehydrogenase (ALDH-2) sowie die Bildung reaktiver Sauerstoff- und Stickstof…

Perspectives in Clinical Hemorheology and Microcirculation: Review of the Conference of the German Society for Clinical Microcirculation and Hemorheology 2010

During the 29th conference of the German Society for Clinical Microcirculation and Hemorheology – held in the Freie Universitat Berlin a broad range of different topics of experimental and clinical studies in the field were presented. A special spotlight was dedicated to the Conference President’s (Prof. Dr. J. Plendl, Head of the Department of Veterinary Anatomy) scientific area “Anatomical and Experimental Microcirculation” [5, 6, 9, 13]. Of special interest were the angiogenetic studies: Examinations of the influence of PDGF-BB on adipose-tissue derived stem cells and how these influence angiogenesis [9] and the angiogenesis and healing with non-shrinking, fast degradable PLGA/CaP scaffo…

Absorb Bioresorbable Scaffold Versus Xience Metallic Stent for Prevention of Restenosis Following Percutaneous Coronary Intervention in Patients at High Risk of Restenosis: Rationale and Design of the COMPARE ABSORB Trial

Abstract Background The advent of bioresorbable vascular scaffolds (BVS) was considered as a potential improvement in percutaneous coronary intervention (PCI) after the groundbreaking development of drug eluting stents (DES). However, the clinical performance, long-term safety and efficacy of BVS in complex coronary lesions remain uncertain. COMPARE ABSORB, a multicenter, single blind, prospective randomized trial, aims to compare the clinical outcomes between the Absorb BVS and Xience everolimus-eluting metallic stent (EES) in patients with coronary artery disease and a high risk of restenosis. Design COMPARE ABSORB is designed to enroll 2100 patients at up to 45 European sites. Enrolled p…

Organic Nitrates and Nitrate Tolerance—State of the Art and Future Developments

The hemodynamic and antiischemic effects of nitroglycerin (GTN) are lost upon chronic administration due to the rapid development of nitrate tolerance. The mechanism of this phenomenon has puzzled several generations of scientists, but recent findings have led to novel hypotheses. The formation of reactive oxygen and nitrogen species in the mitochondria and the subsequent inhibition of the nitrate-bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) appear to play a central role, at least for GTN, that is, bioactivated by ALDH-2. Importantly, these findings provide the opportunity to reconcile the two “traditional” hypotheses of nitrate tolerance, that is, the one postulating …

Nitroglycerine causes mitochondrial reactive oxygen species production: In vitro mechanistic insights

Background Nitroglycerine (GTN) is an organic nitrate that has been used for more than 100 years. Despite its widespread clinical use, several aspects of the pharmacology of GTN remain elusive. In a recent study, the authors of the present study showed that GTN causes opening of the mitochondrial permeability transition pore (mPTP) and mitochondrial production of reactive oxygen species (ROS). Objective In the present study, it was tested whether GTN-induced ROS production depends on mitochondrial potassium ATP-dependent channel or mPTP opening, and/or GTN biotransformation. Methods and results Isolated rat heart mitochondria were incubated with succinate (a substrate for complex II) and GT…

β-Blockers in Patients With Intermittent Claudication and Arterial Hypertension

The use of β-receptor blockers in peripheral arterial disease is controversial for their impact on vasomotor tone. The β-blocker nebivolol possesses vasodilating, endothelium-dependent, NO-releasing properties that might be beneficial in peripheral arterial disease. The aim of the study was to evaluate the effects and tolerability of nebivolol in comparison with metoprolol in these patients. A total of 128 patients with intermittent claudication and essential hypertension were included and double-blind randomized to receive 5 mg of nebivolol (N=65) or 95 mg of metoprolol (N=63) once daily. End points were changes in ankle-brachial index, initial and absolute claudication distance, endothel…

Bioresorbable Everolimus-Eluting Vascular Scaffold for Long Coronary Lesions

Abstract Objectives The authors sought to investigate 1-year outcomes in patients treated with bioresorbable everolimus-eluting vascular scaffolds (BVS) for “long coronary lesions.” Background The present substudy derived from the GHOST-EU registry included 1,722 lesions in 1,468 consecutive patients, enrolled between November 2011 and September 2014 at 11 European centers. Methods The lesions were divided into 3 groups according to continuous BVS length: 1) shorter than 30 mm; 2) between 30 and 60 mm; and 3) longer than 60 mm. Primary device-oriented endpoint (target lesion failure [TLF]) was defined as a combination of cardiovascular death, target vessel myocardial infarction, or clinical…

Contemporary practice and technical aspects in coronary intervention with bioresorbable scaffolds : a European perspective

Aims Next to patient characteristics, the lack of a standardised approach for bioresorbable vascular scaffold (BVS) implantation is perceived as a potential explanation for the heterogeneous results reported so far. To provide some guidance, we sought to find a consensus on the best practices for BVS implantation and management across a broad array of patient and lesion scenarios. Methods and results Fourteen European centres with a high volume of BVS procedures combined their efforts in an informal collaboration. To get the most objective snapshot of different practices among the participating centres, a survey with 45 multiple choice questions was prepared and conducted. The results of th…

Setting the Stage: How to Perform Intracoronary Pressure Measurements

FFR has become an established technology, and alternative approaches, like the instantaneous flow reserve (iFR), are currently being validated. FFR and iFR are generally easy to perform and interpret, but, as with all other technologies, oversimplification also carries risks. In the first chapter of this book, we present the basics of FFR measurements, including basic tips and tricks, and a short introduction to the devices available on the market.

Sex differences in early carotid atherosclerosis (from the community-based Gutenberg-Heart Study).

The objectives of this study were to describe gender differences in intima-media thickness (IMT) in a community-based population study and to define normal IMT values for healthy men and women. In total, 4,814 participants (aged 35 to 74 years; 2,433 men, 2,381 women) from the Gutenberg-Heart Study (GHS) were included. IMT was measured at both common carotid arteries using an edge detection system. Median IMT was 0.62 mm (25th percentile 0.55, 75th percentile 0.70) in women and 0.65 mm (25th percentile 0.57, 75th percentile 0.75) in men and was significantly associated with age (p0.0001). On multivariate analysis, advanced age, smoking, and arterial hypertension were positively associated w…

Sex-specific differences drive temporal trends and outcomes of patients hospitalized for heart failure in Germany

Despite remarkable improvements in treatment of cardiovascular disease, heart failure (HF) is still characterized by high mortality rate. Sex-specific differences in HF have been described, but underlying reasons are widely unexplored.The nationwide German inpatient sample (2005-2016) was used for this sex-specific analyses. Temporal trends on hospitalizations, mortality, and treatments were analysed and independent predictors of adverse outcomes identified.The analysis comprises 4,538,977 hospitalizations due to HF (52.0%women) in Germany (2005-2016). Although women were older (median 82(IQR75-87) vs.76(69-82),P  0.001), coronary artery disease (CAD, 50.3% vs. 30.7%,P  0.001) was more prev…

High-Grade Epicardial Stenosis with Microvascular Compensation

As described in Chap. 32, FFR and CFR should—in theory—provide at least in part concordant results: an impaired FFR should always be associated with an impaired CFR (as a demonstration that the epicardial stenosis limits the maximum achievable blood flow) and vice versa. Exceptions are, however, very frequent.

Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2)

Abstract Aims Electronic (e)-cigarettes have been marketed as a ‘healthy’ alternative to traditional combustible cigarettes and as an effective method of smoking cessation. There are, however, a paucity of data to support these claims. In fact, e-cigarettes are implicated in endothelial dysfunction and oxidative stress in the vasculature and the lungs. The mechanisms underlying these side effects remain unclear. Here, we investigated the effects of e-cigarette vapour on vascular function in smokers and experimental animals to determine the underlying mechanisms. Methods and results Acute e-cigarette smoking produced a marked impairment of endothelial function in chronic smokers determined b…

Characterization of New Organic Nitrate Hybrid Drugs Covalently Bound to Valsartan and Cilostazol

Background and Purpose: Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. With the present studies we synthesized and characterized new organic nitrate hybrid molecules. Compounds CLC-1265 (valsartan mononitrate) and CLC-1280 (valsartan dinitrate) are derivatives of the angiotensin receptor blocker valsartan, with CLC-1265 containing a single organic nitrate linker and CLC-1280 also containing a second, different linker. Compounds CLC-2000 (cilostazol mononitrate) and CLC-2100 (cilostazol dinitrate) are nitrate derivatives of the phosphodiesterase III inhibitor cilostazol. All compounds are designed as hybrid molecu…

Early and midterm outcomes of bioresorbable vascular scaffolds for ostial coronary lesions: insights from the GHOST-EU registry.

Aims: We aimed to investigate the outcomes of bioresorbable vascular scaffolds (BVS) in coronary ostial lesions. Ostial lesions represent a challenging angiographic subset, with higher event rates compared with non-ostial lesions. BVS might be associated with advantages over the long term, but their safety in this setting remains to be explored. Methods and results: Procedural and 12-month follow-up data from consecutive patients treated with BVS for lesions located at the ostium of the right (RCA), left anterior (LAD) or circumflex (LCX) coronary in 11 European centres were collected. The primary device-oriented endpoint was defined as a combination of cardiovascular death, target vessel m…

Rationale, design and baseline characteristics of the MyoVasc study: A prospective cohort study investigating development and progression of heart failure.

Abstract Background Heart failure (HF) is a poly-aetiological syndrome with large heterogeneity regarding clinical presentation, pathophysiology, clinical outcome and response to therapy. The MyoVasc study (NCT04064450) is an epidemiological cohort study investigating the development and progression of HF. Methods The primary objective of the study is (a) to improve the understanding of the pathomechanisms of HF across the full spectrum of clinical presentation, (b) to investigate the current clinical classifications of HF, and (c) to identify and characterize homogeneous subgroups regarding disease development using a systems-oriented approach. Worsening of HF, that is, the composite of tr…

Psychodynamic motivation and training program (PMT) for the secondary prevention in patients with stable coronary heart disease : study protocol for a randomized controlled trial of feasibility and effects

TCT-403 Peripheral Endothelial Function and Sympathetic Influence on Dermal Microcirculation Correlate with Long-Term Blood Pressure Response in Renal Denervation Patients

Percutaneous coronary intervention with everolimus-eluting bioresorbable vascular scaffolds in routine clinical practice: early and midterm outcomes from the European multicentre GHOST-EU registry

Clinical data on the early and midterm outcomes of bioresorbable vascular scaffolds (BVS) in routine clinical practice are limited. To fill this gap, we report on the early and midterm clinical outcomes of PCI with everolimus-eluting BVS from the large multicentre GHOST-EU registry.Between November 2011 and January 2014, 1,189 patients underwent percutaneous coronary intervention with one or more BVS (Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) at 10 European centres. The primary outcome of interest was target lesion failure (TLF), defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularisation (TLR). A total of 1…

Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications

Abstract Systolic and diastolic myocardial dysfunction has been demonstrated to be associated with an activation of the circulating and local renin–angiotensin–aldosterone system (RAAS), and with a subsequent inappropriately increased production of reactive oxygen species (ROS). While, at low concentrations, ROS modulate important physiological functions through changes in cellular signalling and gene expression, overproduction of ROS may adversely alter cardiac mechanics, leading to further worsening of systolic and diastolic function. In addition, vascular endothelial dysfunction due to uncoupling of the nitric oxide synthase, activation of vascular and phagocytic membrane oxidases or mit…

Reproducibility of FFR

This chapter describes the repeatability of FFR assessments using IC and IV infusions of Adenosine. Further, it demonstrates that is possible to assess FFR with a diagnostic catheter.

When the Pd/Pa Is Already Significant: A “Quick and Clean” FFR

The assessment of FFR for a single stenosis may also be rapid and not require hyperemia if the Pd/Pa gradient already reaches significance before the vasodilator is administered. In this case the resting Pd/Pa was 0.45, demonstrating that the stenosis was relevant even before hyperemia was achieved.

Annoyance to different noise sources is associated with atrial fibrillation in the Gutenberg Health Study

Abstract Background Annoyance is a common reaction in populations exposed to environmental noise and is associated with cardiovascular diseases. We investigated for the first time the existence of an association between noise annoyance and atrial fibrillation (AF). Methods and results Cross-sectional data from 14,639 participants of the Gutenberg Health Study were collected between 2007 and 2012. Annoyance from road traffic, aircraft, railways, industrial/construction and neighbourhood noise during daytime and sleep were collected from all participants through questionnaires using a 5-point scale. AF was assessed via self-reported medical history and/or documentation of AF on the study elec…

The distribution of whole blood viscosity, its determinants and relationship with arterial blood pressure in the community: cross-sectional analysis from the Gutenberg Health Study.

Background: Blood viscosity has a role in modulating cardiovascular homeostasis; changes in this parameter have been associated with cardiovascular mortality and morbidity. However, it remains unclear whether these changes are (1) involved in the pathophysiology of disease, (2) an epiphenomenon, or (3) the expression of counterregulatory mechanisms. We report data on the normal values of blood viscosity and its association with cardiovascular risk factors, prevalent cardiovascular disease, and blood pressure in a large population-based cohort study. Methods and results: Viscosity was calculated using validated formulae and its associations were explored in 15,010 participants (mean 55.0, mi…

Effects of gaseous and solid constituents of air pollution on endothelial function

Abstract Ambient air pollution is a leading cause of non-communicable disease globally. The largest proportion of deaths and morbidity due to air pollution is now known to be due to cardiovascular disorders. Several particulate and gaseous air pollutants can trigger acute events (e.g. myocardial infarction, stroke, heart failure). While the mechanisms by which air pollutants cause cardiovascular events is undergoing continual refinement, the preponderant evidence support rapid effects of a diversity of pollutants including all particulate pollutants (e.g. course, fine, ultrafine particles) and gaseous pollutants such as ozone, on vascular function. Indeed alterations in endothelial function…

Hybrid Coronary Percutaneous Treatment with Metallic Stents and Everolimus-Eluting Bioresorbable Vascular Scaffolds: 2-years Results from the GABI-R Registry

The limitations of the first-generation everolimus-eluting coronary bioresorbable vascular scaffolds (BVS) have been demonstrated in several randomized controlled trials. Little data are available regarding the outcomes of patients receiving hybrid stenting with both BVS and drug-eluting stents (DES). Of 3144 patients prospectively enrolled in the GABI-Registry, 435 (age 62 &plusmn

Transmural myocardial ischaemia complicating recovery after dobutamine-atropine stress echocardiography in patients with non-significant coronary artery disease: insights from invasive assessment of coronary physiology

In the proposed selection of cases, traditional imaging is integrated with contemporary diagnostic tools available in the cath-lab to navigate the potential mechanisms underlying a very rare complication occurring in the recovery phase of dobutamine-atropine stress echocardiography. The data, collected in a time frame of nearly 15 years, provide interesting elements to possibly evolve from speculative considerations to plausible confirmation of the candidate pathophysiological mechanism mediating the occurrence of transmural myocardial ischaemia after beta-blockers administration.

Identification of acute myocardial infarction in elderly patients using optimized highly sensitive troponin I thresholds

Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs. Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients &gt; 70 years were classified as elderly. hs-cTnI was measured upon admission. Results: Around 34.7% of 2903 patients were…

Interventional femoral “crossover” bypass for peripheral ischaemia under cardiocirculatory support with the Impella CP heart pump

Association of Global Longitudinal Strain With Clinical Status and Mortality in Patients With Chronic Heart Failure.

IMPORTANCE: Global longitudinal strain (GLS) is an emerging echocardiographic biomarker of cardiac function in heart failure (HF). Evidence from large-scale studies comprehensively investigating GLS for its association with clinical phenotypes and mortality in asymptomatic and symptomatic chronic HF is limited. OBJECTIVE: To assess the factors associated with GLS and its prognostic value in patients with chronic HF. DESIGN, SETTING, AND PARTICIPANTS: The observational, prospective MyoVasc cohort study enrolled 3289 individuals with asymptomatic to symptomatic HF between January 17, 2013, and April 27, 2018. The median follow-up was 3.2 years (interquartile range, 2.0-4.0 years). Participant…

Tolerance to nitroglycerin-induced preconditioning of the endothelium: a human in vivo study

Damage and dysfunction of the vascular endothelium critically influence clinical outcomes after ischemia and reperfusion (I/R). Brief exposure to organic nitrates can protect the vascular endothelium from I/R injury via a mechanism that is similar to ischemic preconditioning and is independent of hemodynamic changes. The clinical relevance of these protective effects clearly depends on whether they can be sustained over time. Twenty-four healthy (age 25–32) male volunteers were randomized to receive 1) transdermal nitroglycerin (GTN; 0.6 mg/h) administered for 2 h on 1 day only, 2) transdermal GTN for 2 h/day for 7 days, or 3) continuous therapy with transdermal GTN for 7 days. Eight volunt…

Inflammatory markers and cardiovascular risk in the metabolic syndrome

Elevated blood glucose, obesity, high blood pressure, elevated triglycerides and low high density lipoprotein (HDL) cholesterol are well accepted risk factors in the development of coronary artery disease. Clustering of at least three of these factors in an individual is defined as metabolic syndrome (MetS). Obesity is a central pathological mechanism in the disease and it is expected that the incidence of this condition will increase dramatically within the next years. The visceral adipose tissue is not only an energy depot but also an endocrine organ which produces a large number of bioactive molecules, the so called adipokines. In the setting of obesity, the over-production of proinflamm…

Effect of implantation technique on outcomes in patients receiving bioresorbable scaffolds in various clinical scenarios

ABSTRACT Introduction and objectives: The PSP (pre-dilation, sizing and post-dilation) score, derived from the GHOST-EU registry, has evaluated the relationship between the implantation technique of bioresorbable scaffolds and the clinical outcomes. The objective was to perform an external validation of the PSP technique and to determine its effect on adverse cardiac events in various clinical and anatomical scenarios. Methods: Data from the REPARA registry (2230 patients) were used for external validation, whereas a common database combining REPARA and GHOST-EU (3250 patients) data was used to evaluate the effect of PSP technique in various clinical and anatomical scenarios. PSP-1 and PSP-…

Threshold FFR, Impaired CFR, and IMR: Macrovascular or Microvascular Disease?

An 80-year-old patient with recurrent stable angina underwent coronary angiography. An intermediate lesion was demonstrated at the ostium of the LAD, which was studied with FFR. The finding of an abnormal CFR was an incidental one.

Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial.

Background The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study (‘CLEOPATRA’ study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. Methods and results A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo ( n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 wee…

Noninvasive peripheral vascular function and atrial fibrillation in the general population.

Background Arterial stiffness is a strong predictor of atrial fibrillation in the community. Whether noninvasively measured conduit artery function and peripheral vascular reactivity are related to atrial fibrillation remains unknown. Methods and results In 15 010 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 50.5% men, we determined noninvasive vascular function by flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT) in relation to manifest atrial fibrillation (N = 466). Patients with atrial fibrillation exhibited a higher mean brachial artery diameter [4.81 mm (4.17, 5.33) in atrial fibrillation vs. 4.31 mm (3.67, 4.93)] and baseline p…

Phenotypic characterisation of pro-inflammatory monocytes and dendritic cells in peripheral arterial disease

SummaryAtherosclerosis is a chronic inflammatory process involving antigen-presenting cells like monocytes and dendritic cells (DC). The aim of this study was to perform a phenotypic characterisation of these cell types in patients with different degrees of peripheral arterial disease (PAD). Sixty patients with PAD [N= 30 intermittent claudication (IC), N= 30 critical limb ischemia (CLI)] and 30 controls were included. Peripheral blood leucocytes were analysed from peripheral blood by flow cytometry using different gating strategies to directly identify and analyse monocytes, myeloid DC, (mDC) and plasmacytoid DC (pDC). PAD patients showed a significantly higher proportion of proinflammator…

Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition.

Aims Dipeptidyl peptidase-4 (DPP-4) inhibitors are a novel class of drugs for the treatment of hyperglycaemia. Preliminary evidence suggests that their antioxidant and anti-inflammatory effects may have beneficial effects on the cardiovascular complications of diabetes. In the present study, we investigate in an experimental sepsis model whether linagliptin exerts pleiotropic vascular effects independent of its glucose-lowering properties. Methods and results Linagliptin (83 mg/kg chow for 7days) was administered in a rat model of lipopolysaccharide (LPS) (10 mg/kg, single i.p. dose/24 h)-induced sepsis. Vascular relaxation, reactive oxygen species (ROS) formation, expression of NADPH oxida…

Clinical outcomes of patients with diabetes mellitus treated with Absorb bioresorbable vascular scaffolds: a subanalysis of the European Multicentre GHOST-EU Registry.

Background Data on the clinical performance of bioresorbable scaffolds in patients with diabetes mellitus (DM) are still limited. The present study reported 1-year clinical outcomes associated with the use of everolimus-eluting bioresorbable vascular scaffolds (Absorb BVS; Abbott Vascular, Santa Clara, CA) in DM patients. Methods and Results This was a subanalysis from the GHOST-EU (Gauging coronary Healing with biOresorbable Scaffolding plaTforms in Europe) multicenter retrospective registry including patients treated with Absorb BVS between November 2011 and September 2014. In this study, a comparative analysis stratified according to DM was performed. The primary endpoint was target lesi…

Thrombosis, fracture, and percutaneous removal of a patent foramen ovale closure device 1 month after successful deployment

Several different devices have been developed for the percutaneous closure of interatrial defects and patent foramen ovale. Although the implantation of these devices is both safe and effective, a number of complications, both in the early and the late follow-up, may occur. We describe a case of device fracture manifested early (1 month after implantation) with the formation of massive thrombosis on the right atrial disc. The patient was treated with anticoagulants and the device was percutaneously retrieved. Our images allowed early noninvasive therapy and emphasize the need for echocardiographic follow-up early after implantation. © 2010 Wiley-Liss, Inc.

Critical limb ischaemia is characterised by an increased production of whole blood reactive oxygen species and expression of TREM-1 on neutrophils

Atherosclerosis is a chronic inflammatory process involving polymorphonuclear neutrophils (PMN) and formation of reactive oxygen species (ROS). The aim of the present study was to investigate the phenotype of inflammatory cells in regard to the expression of triggering receptor expressed on myeloid cells (TREM)-1 and its soluble form (sTREM-1) as well as its relationship with oxidative stress in peripheral artery disease (PAD) patients.In total 90 patients with PAD (N = 30 intermittent claudication (IC)300 m absolute walking distance, N = 30 IC300 m absolute walking distance, N = 30 critical limb ischaemia (CLI)) and 30 control persons were included. ROS formation was measured at basal or s…

Long-term outcome after drug-eluting stents implantation: Target lesion versus nontarget lesion repeated intervention

Abstract We sought to investigate the relative clinical significance of target and nontarget lesions repeated percutaneous coronary intervention (re-PCI) in patients implanted with drug-eluting stents (DES). Out of 2626 consecutive DES patients, we retrospectively selected 166 (6.3%; 123 males, aged 65±10years) who had a clinically-driven re-PCI over a mean follow-up of 15months. Seventy-five patients (45%) underwent the second procedure for disease progression in nontarget lesions (nontarget lesion re-PCI group) while 91 (55%) showed target lesion in-stent restenosis or thrombosis (target lesion re-PCI group), with no significant intergroup difference in the temporal trends of re-PCI. The …

Characterization and referral patterns of ST-elevation myocardial infarction patients admitted to chest pain units rather than directly to catherization laboratories : Data from the German Chest Pain Unit Registry

Abstract Background Direct transfer to the catheterization laboratory for primary percutaneous coronary intervention (PCI) is standard of care for patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, a significant number of STEMI-patients are initially treated in chest pain units (CPUs) of admitting hospitals. Thus, it is important to characterize these patients and to define why an important deviation from recommended clinical pathways occurs and in particular to quantify the impact of deviation on critical time intervals. Methods and results 1679 STEMI patients admitted to a CPU in the period from 2010 to 2015 were enrolled in the German CPU registry (8.5% of 19…

State of the Art-High-Sensitivity Troponins in Acute Coronary Syndromes.

In cases of suspected acute coronary syndrome (ACS), rapid and accurate diagnosis is essential to establish effective evidence-based medical treatment. Patients' history, clinical examination, 12-lead electrocardiogram, and cardiac biomarkers are cornerstones in initial management. Since high-sensitivity cardiac troponins were established, they have markedly expedited and revolutionized rule-in and rule-out pathways of patients with ACS and changed our everyday clinical practice. Thus, they have become an indispensable tool in daily routine in emergency units. This review focuses on historical and contemporary standards in laboratory biomarkers of myocardial injury and discusses their impli…

Pentaerythrityl Tetranitrate and Nitroglycerin, but not Isosorbide Mononitrate, Prevent Endothelial Dysfunction Induced by Ischemia and Reperfusion

Background— Short term exposure to nitroglycerin (GTN) has protective properties that are similar to ischemic preconditioning. Whether other organic nitrates such as pentaerithrityl tetranitrate (PETN) and isosorbide mononitrate (ISMN) have similar protective effects has not been explored. Methods and Results— In a randomized, parallel, double blind, controlled trial, 37 healthy young volunteers received no therapy (n=10), transdermal GTN 1.2 mg for 2 hours (n=9), PETN 80 mg (n=9), or ISMN 40 mg (n=9). Twenty-four hours later, endothelium-dependent flow-mediated vasodilation (FMD) was measured before and after local exposure to ischemia and reperfusion (IR). In the no therapy group, IR blu…

Contrast-Induced Hyperemia and FFR: Slightly Slower but still “Quick and Clean”

Slightly more complex than the previous one, a quick way to induce hyperemia is to inject a contrast bolus. Although the degree of hyperemia reached this way is not as large as with vasodilators, this maneuver can still allow unmasking a gradient.

Cardiovascular effects of nocturnal aircraft noise on healthy volunteers

Background: Nighttime aircraft noise can impair sleep quality and may also increase blood pressure and the risk for myocardial infarction for persons in highly noise exposed residential areas. Pathophysiology and possible susceptibility factors for cardiovascular effects of aircraft noise remain unclear. Methods and results: 75 healthy volunteers (mean age 26 y) were studied for three nights in their homes. One control pattern without noise (Control) and two noise patterns with 30 (Noise 30) or 60 (Noise 60) aircraft noise events were played back in random and blinded order. After each study night flow-mediated dilatation (FMD) of the brachial artery was measured the following the morning. …

Rosuvastatin Prevents Conduit Artery Endothelial Dysfunction Induced by Ischemia and Reperfusion by a Cyclooxygenase-2–Dependent Mechanism

ObjectivesThe purpose of this study was to determine whether single-dose rosuvastatin (40 mg) protects against ischemia and reperfusion (IR)–induced endothelial dysfunction in humans and whether this effect is cyclooxygenase (COX)-2 dependent.BackgroundAnimal studies have demonstrated that rosuvastatin can limit damage and improve recovery after IR.MethodsIn a double-blind, parallel design, 20 volunteers were randomized to a single dose of oral rosuvastatin (40 mg) or placebo. Twenty-four hours later, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protoc…

Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study

Background: Elevated levels of FVIII:c are associated with risk for both venous and arterial thromboembolism. However, no population-based study on the sex-specific distribution and reference ranges of plasma FVIII: c and its cardiovascular determinants is available. Methods: FVIII:c was analyzed in a randomly selected sample of 2533 males and 2440 females from the Gutenberg Health Study in Germany. Multivariable regression analyses for FVIII:c were performed under adjustment for genetic determinants, cardiovascular risk factors and cardiovascular disease. Results and conclusions: Females (126.6% (95% CI: 125.2/128)) showed higher FVIII:c levels than males (121.2% (119.8/122.7)). FVIII:c le…

First Evidence for a Crosstalk Between Mitochondrial and NADPH Oxidase-Derived Reactive Oxygen Species in Nitroglycerin-Triggered Vascular Dysfunction

Chronic nitroglycerin treatment results in development of nitrate tolerance associated with endothelial dysfunction (ED). We sought to clarify how mitochondria- and NADPH oxidase (Nox)-derived reactive oxygen species (ROS) contribute to nitrate tolerance and nitroglycerin-induced ED. Nitrate tolerance was induced by nitroglycerin infusion in male Wistar rats (100 microg/h/4 day) and in C57/Bl6, p47(phox/) and gp91(phox/) mice (50 microg/h/4 day). Protein and mRNA expression of Nox subunits were unaltered by chronic nitroglycerin treatment. Oxidative stress was determined in vascular rings and mitochondrial fractions of nitroglycerin-treated animals by L-012 enhanced chemiluminescence, revea…

Using FFR to Detect Ischemia in Myocardial Bridge Lesions

Beyond atherosclerosis, a number of other phenomena may result in cardiac ischemia. Among these, extracoronary compression due to myocardial bridges may cause a dynamic stenosis and typical angina. The assessment of the hemodynamic relevance and the treatment of such lesions have unique characteristics that are due to the fact that extracoronary compression from myocardial bridges is mostly a systolic phenomenon and is dependent on the inotropic state. The consequence is that other hyperemic stimuli, such as dobutamine, may be more adequate to unveil ischemia in these settings.

Impact of coronary calcification on outcomes after ABSORB scaffold implantation: insights from the GABI-R registry.

OBJECTIVE To investigate the outcomes after bioresorbable scaffold (BRS) implantation in calcified coronary lesions. In calcified coronary lesions, durable metallic drug-eluting stent (DES) implantation is associated with worse clinical outcomes compared to noncalcified lesions. Although not recommended, BRSs were frequently implanted in calcified lesions in clinical practice. Their outcome is not well investigated. METHODS Between November 2013 and January 2016, 3326 patients were enrolled in the German-Austrian ABSORB ReglstRy (GABI-R). Lesion calcification severity was classified into no (n = 1144), mild (n = 1306), and moderate-to-severe (n = 690) calcification. RESULTS Patients with ca…