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Background: Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low‐cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST‐segment elevation myocardial infarction (STEMI) and non‐ST‐segment elevation ACS (NSTE‐ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. Methods: From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE‐ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high‐sensitivity C‐reactive protein (hs‐CRP) and cardiac troponin‐T (hs‐cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni‐ and multivariable regression models were fit to assess associations of BT with future MACE risk. Results: Among patients with STEMI, BT was not predictive of 1‐year MACE, but a U‐shaped relationship between BT and MACE risk was noted in those with NSTE‐ACS (p =.029), translating into a 2.4‐fold (HR, 2.44, 95% CI, 1.16–5.16) increased 1‐year MACE risk in those with BT >36.8°C (reference: 36.6–36.8°C). Results remained robust in multivariable‐adjusted analyses accounting for sex, age, diabetes, renal function and hs‐cTnT. However, when introducing hs‐CRP, the BT‐MACE association did not prevail. Conclusions: In prospectively recruited patients with ACS, initial BT shows a U‐shaped relationship with 1‐year MACE risk among those with NSTE‐ACS, but not in those with STEMI. BT is a broadly available low‐cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti‐inflammatory intervention. Registration: ClinicalTrials.gov Identifier: NCT01000701. [ABSTRACT FROM AUTHOR]

Aim: Heart failure with preserved ejection fraction (HFpEF) remains under‐diagnosed in clinical practice despite accounting for nearly half of all heart failure (HF) cases. Accurate and timely diagnosis of HFpEF is crucial for proper patient management and treatment. In this study, we explored the potential of natural language processing (NLP) to improve the detection and diagnosis of HFpEF according to the European Society of Cardiology (ESC) diagnostic criteria. Methods and results: In a retrospective cohort study, we used an NLP pipeline applied to the electronic health record (EHR) to identify patients with a clinical diagnosis of HF between 2010 and 2022. We collected demographic, clinical, echocardiographic and outcome data from the EHR. Patients were categorized according to the left ventricular ejection fraction (LVEF). Those with LVEF ≥50% were further categorized based on whether they had a clinician‐assigned diagnosis of HFpEF and if not, whether they met the ESC diagnostic criteria. Results were validated in a second, independent centre. We identified 8606 patients with HF. Of 3727 consecutive patients with HF and LVEF ≥50% on echocardiogram, only 8.3% had a clinician‐assigned diagnosis of HFpEF, while 75.4% met ESC criteria but did not have a formal diagnosis of HFpEF. Patients with confirmed HFpEF were hospitalized more frequently; however the ESC criteria group had a higher 5‐year mortality, despite being less comorbid and experiencing fewer acute cardiovascular events. Conclusions: This study demonstrates that patients with undiagnosed HFpEF are an at‐risk group with high mortality. It is possible to use NLP methods to identify likely HFpEF patients from EHR data who would likely then benefit from expert clinical review and complement the use of diagnostic algorithms. [ABSTRACT FROM AUTHOR]

Aims: Cardiac sarcoidosis (CS) is a potentially fatal condition that varies in its clinical presentation. Here, we describe baseline characteristics at presentation along with prognosis and predictors of outcome in a sizable and deeply phenotyped contemporary cohort of CS patients. Methods and results: Consecutive CS patients seen at one institution were retrospectively enrolled after undergoing laboratory testing, electrocardiogram, echocardiography, cardiac magnetic resonance (CMR) imaging and 18F‐flourodeoxyglucose positron emission tomography (FDG‐PET) at baseline. The composite endpoint consisted of all‐cause mortality, aborted sudden cardiac death, major ventricular arrhythmic events, heart failure hospitalization and heart transplantation. A total of 319 CS patients were studied (67% male, 55.4 ± 12 years). During a median follow‐up of 2.2 years (range: 1 month–11 years), 8% of patients died, while 33% reached the composite endpoint. The annualized mortality rate was 2.7% and the 5‐ and 10‐year mortality rates were 6.2% and 7.5%, respectively. Multivariate analysis showed serum brain natriuretic peptide (BNP) levels (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.34–4.31, p = 0.003), CMR left ventricular ejection fraction (LVEF) (HR 0.96, 95% CI 0.94–0.98, p < 0.0001) and maximum standardized uptake value of FDG‐PET (HR 1.11, 95% CI 1.04–1.19, p = 0.001) to be independent predictors of outcome. These findings remained robust for different patient subgroups. Conclusion: Cardiac sarcoidosis is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP levels, lower LVEF and more active myocardial inflammation were independent predictors of outcomes. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between heart failure (HF) and respiratory tract infections, specifically lower respiratory tract infections (LRTI). The burden of comorbidities in patients with HF exposes them to a higher risk of non-cardiovascular events, including infections. LRTIs, such as pneumonia, are common in patients with HF and can lead to HF decompensation or be a consequence of it, increasing the risk of hospitalizations and mortality. The article also explores the potential protective role of HF drugs, specifically empagliflozin, in preventing LRTIs. The study found that empagliflozin was associated with a lower risk of incident LRTI compared to a placebo. However, there was no impact on the incidence of COVID-19. Further research is needed to confirm these findings and explore the impact of SGLT2 inhibitors on LRTI risk in patients with HF. [Extracted from the article]

Aims: Health‐related quality of life (HRQoL) is highly relevant in cancer and often assessed with the EORTC QLQ‐C30. Cardiovascular HRQoL in cancer can be measured with the ESC HeartQoL questionnaire. We compared these instruments and examined their prognostic value. Methods and results: Summary scores for EORTC QLQ‐C30 (0–100 points) and ESC HeartQoL (0–3 points) questionnaires were prospectively assessed in 290 patients with mostly advanced cancer (stage 3/4: 81%, 1‐year mortality: 36%) and 50 healthy controls (similar age and sex). Additionally, physical function and activity assessments were performed. Both questionnaires demonstrated reduced HRQoL in patients with cancer versus controls (EORTC QLQ‐C30: 67 ± 20 vs. 91 ± 11, p < 0.001; ESC HeartQoL: 1.8 ± 0.8 vs. 2.7 ± 0.4, p < 0.001). The instruments were strongly correlated with each other (summary scores [r = 0.76], physical [r = 0.81], and emotional subscales [r = 0.75, all p < 0.001]) and independently associated with all‐cause mortality (best cut‐offs: EORTC QLQ‐C30 <82.69: hazard ratio [HR] 2.33, p = 0.004; ESC HeartQoL <1.50: HR 1.85, p = 0.004 – adjusted for sex, age, left ventricular ejection fraction, N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP], high‐sensitivity troponin T, cancer stage/type), with no differences in the strength of the association by sex (p‐interaction > 0.9). Combining both questionnaires identified three risk groups with highest mortality in patients below both cut‐offs (vs. patients above both cut‐offs: HR 3.60, p < 0.001). Patients with results below both cut‐offs, showed higher NT‐proBNP and reduced physical function and activity. Conclusions: The EORTC QLQ‐C30 and ESC HeartQoL – assessing cancer and cardiovascular HRQoL – are both associated with increased mortality in cancer patients, with even greater stratification by combing both. Reduced HRQoL scores were associated with elevated cardiovascular biomarkers and decreased functional status. [ABSTRACT FROM AUTHOR]

Over 10 million doses of COVID‐19 vaccines based on RNA technology, viral vectors, recombinant protein, and inactivated virus have been administered worldwide. Although generally very safe, post‐vaccine myocarditis can result from adaptive humoral and cellular, cardiac‐specific inflammation within days and weeks of vaccination. Rates of vaccine‐associated myocarditis vary by age and sex with the highest rates in males between 12 and 39 years. The clinical course is generally mild with rare cases of left ventricular dysfunction, heart failure and arrhythmias. Mild cases are likely underdiagnosed as cardiac magnetic resonance imaging (CMR) is not commonly performed even in suspected cases and not at all in asymptomatic and mildly symptomatic patients. Hospitalization of symptomatic patients with electrocardiographic changes and increased plasma troponin levels is considered necessary in the acute phase to monitor for arrhythmias and potential decline in left ventricular function. In addition to evaluation for symptoms, electrocardiographic changes and elevated troponin levels, CMR is the best non‐invasive diagnostic tool with endomyocardial biopsy being restricted to severe cases with heart failure and/or arrhythmias. The management beyond guideline‐directed treatment of heart failure and arrhythmias includes non‐specific measures to control pain. Anti‐inflammatory drugs such as non‐steroidal anti‐inflammatory drugs, and corticosteroids have been used in more severe cases, with only anecdotal evidence for their effectiveness. In all age groups studied, the overall risks of SARS‐CoV‐2 infection‐related hospitalization and death are hugely greater than the risks from post‐vaccine myocarditis. This consensus statement serves as a practical resource for physicians in their clinical practice, to understand, diagnose, and manage affected patients. Furthermore, it is intended to stimulate research in this area. [ABSTRACT FROM AUTHOR]

Background: Microvesicles are vesicles shed by plasma membranes following cell activation and apoptosis. The role of lymphocyte‐derived microvesicles in endothelial function remains poorly understood. Methods: CD4+ T cells isolated from peripheral blood of healthy human donors were stimulated using anti‐CD3/anti‐CD28‐coated beads. Proteomic profiling of microvesicles was performed using linear discriminant analysis (LDA) from activated T cells (MV.Act) and nonactivated T cells (MV.NAct). In addition, data processing analysis was performed using MaxQUANT workflow. Differentially expressed proteins found in MV.Act or MV.NAct samples with identification frequency = 100%, which were selected by both LDA (p <.01) and MaxQUANT (p <.01) workflows, were defined as "high‐confidence" differentially expressed proteins. Functional effects of MV.Act on human primary microvascular endothelial cells were analysed. Results: T cells released large amounts of microvesicles upon stimulation. Proteomic profiling of microvesicles using LDA identified 2279 proteins (n = 2110 and n = 851 proteins in MV.Act and MV.NAct, respectively). Protein–protein interaction network models reconstructed from both differentially expressed proteins (n = 594; LDA p ≤.01) and "high‐confidence" differentially expressed proteins (n = 98; p ≤.01) revealed that MV.Act were enriched with proteins related to immune responses, protein translation, cytoskeleton organisation and TNFα‐induced apoptosis. For instance, MV.Act were highly enriched with IFN‐γ, a key proinflammatory pathway related to effector CD4+ T cells. Endothelial cell incubation with MV.Act induced superoxide generation, apoptosis, endothelial wound healing impairment and endothelial monolayer barrier disruption. Conclusions: T cell receptor‐mediated activation of CD4+ T cells stimulates the release of microvesicles enriched with proteins involved in immune responses, inflammation and apoptosis. T cell‐derived microvesicles alter microvascular endothelial function and barrier permeability, potentially promoting tissue inflammation. [ABSTRACT FROM AUTHOR]

Aims: Epidemiologic evidence links ischemic stroke to age, yet the mechanisms that underlie the specific and independent effects of age on stroke remain elusive, impeding the development of targeted treatments. This study tested the hypothesis that age directly aggravates stroke outcomes and proposes inflamm‐aging as a mediator and potential therapeutic target. Methods: 3 months‐ (young) and 18‐20 months‐old (old) mice underwent transient middle cerebral artery occlusion (tMCAO) for 30 minutes followed by 48 hours of reperfusion. Old animals received weekly treatment with the TNF‐α neutralizing antibody adalimumab over 4 weeks before tMCAO in a separate set of experiments. Plasma levels of TNF‐ α were assessed in patients with ischemic stroke and correlated with age and outcome. Results: Old mice displayed larger stroke size than young ones with increased neuromotor deficit. Immunohistochemical analysis revealed impairment of the blood‐brain barrier in old mice, i.e. increased post‐stroke degradation of endothelial tight junctions and expression of tight junctions‐digesting and neurotoxic matrix metalloproteinases. At baseline, old animals showed a broad modulation of several circulating inflammatory mediators. TNF‐α displayed the highest increase in old animals and its inhibition restored the volume of stroke, neuromotor performance, and survival rates of old mice to the levels observed in young ones. Patients with ischemic stroke showed increased TNF‐α plasma levels which correlated with worsened short‐term neurological outcome as well as with age. Conclusions: This study identifies TNF‐α as a causative contributor to the deleterious effect of aging on stroke and points to inflamm‐aging as a mechanism of age‐related worsening of stroke outcomes and potential therapeutic target in this context. Thus, this work provides a basis for tailoring novel stroke therapies for the particularly vulnerable elderly population. [ABSTRACT FROM AUTHOR]

Aims: The mortality in cardiogenic shock (CS) is high. The role of specific mechanical circulatory support (MCS) systems is unclear. We aimed to compare patients receiving Impella versus ECLS (extracorporal life support) with regard to baseline characteristics, feasibility, and outcomes in CS. Methods and results: This is a retrospective cohort study including CS patients over 18 years with a complete follow‐up of the primary endpoint and available baseline lactate level, receiving haemodynamic support either by Impella 2.5 or ECLS from two European registries. The decision for device implementation was made at the discretion of the treating physician. The primary endpoint of this study was all‐cause mortality at 30 days. A propensity score for the use of Impella was calculated, and multivariable logistic regression was used to obtain adjusted odds ratios (aOR). In total, 149 patients were included, receiving either Impella (n = 73) or ECLS (n = 76) for CS. The feasibility of device implantation was high (87%) and similar (aOR: 3.14; 95% CI: 0.18–56.50; P = 0.41) with both systems. The rates of vascular injuries (aOR: 0.95; 95% CI: 0.10–3.50; P = 0.56) and bleedings requiring transfusions (aOR: 0.44; 95% CI: 0.09–2.10; P = 0.29) were similar in ECLS patients and Impella patients. The use of Impella or ECLS was not associated with increased odds of mortality (aOR: 4.19; 95% CI: 0.53–33.25; P = 0.17), after correction for propensity score and baseline lactate level. Baseline lactate level was independently associated with increased odds of 30 day mortality (per mmol/L increase; OR: 1.29; 95% CI: 1.14–1.45; P < 0.001). Conclusions: In CS patients, the adjusted mortality rates of both ECLS and Impella were high and similar. The baseline lactate level was a potent predictor of mortality and could play a role in patient selection for therapy in future studies. In patients with profound CS, the type of device is likely to be less important compared with other parameters including non‐cardiac and neurological factors. [ABSTRACT FROM AUTHOR]

LoDoCo2 was designed as a multicentre, event-driven, double-blind RCT in which patients with chronic CAD on conventional therapy and tolerant to colchicine were enrolled during a run-in phase of 30 days. Am Heart J. 2019; 218 (LDLc): 46 - 56. 11 The LoDoCo2 Trial: A randomised controlled trial on the effect of low dose Colchicine for secondary prevention of cardiovascular disease in patients with established, stable coronary artery disease. [Extracted from the article]

The clinical benefits of renal denervation are still under discussion, since randomized controlled clinical studies have provided inconsistent results. The present retrospective study examined the clinical effects of renal denervation with focus on office blood pressure, heart rate, and changes in renal function. Patients with treatment‐resistant hypertension (blood pressure ≥ 140/90 mm Hg in spite of 3 antihypertensive drugs including a diuretic) underwent renal denervation at the University Hospital of Zurich, Switzerland and were followed up until 36 months. Renal denervation was performed using 3 different renal denervation systems. The primary outcome consisted of change in office blood pressure, heart rate, and plasma creatinine at 1, 6, 12, 24, and 36 months after renal denervation. 58 patients underwent renal denervation between August 2010 and December 2017. After exclusion, 50 patients were included in the analyses. At 36 months, the mean office systolic and diastolic blood pressure change was −26.4/‐8.8 mm Hg (95% CI: −34.6 to −18.2/‐13.5 to −4.2 mm Hg; P <.001 for both). Office heart rate showed no significant change during follow‐up (P =.361). Plasma creatinine increased from 90.6 µmol/L (95% CI: 82.1 to 99.0 µmol/L) at baseline to 102.1 µmol/L (95% CI: 95.8 to 108.3 µmol/L) at 36 months (P =.007). No major adverse events occurred. Renal denervation is a safe and effective procedure for patients with treatment‐resistant hypertension with a clinically significant antihypertensive effect. Further randomized trials are needed to determine the specific context within which renal denervation should be considered a therapeutic option in antihypertensive care. [ABSTRACT FROM AUTHOR]

Over the last century, Western societies experienced a demographic shift driven by increased lifespan and decreased fertility, resulting in the subversion of the world's demographic pyramid. In ageing societies, cardiovascular diseases are the major cause of morbidity and mortality, thus representing a major societal and economic burden. Indeed, ageing associates with the deterioration of a genetic network implicated in senescence and longevity, orchestrating deleterious cellular processes that converge in the structural and functional decline of both the myocardium and the vasculature. In this review, we revise a compendium of genes involved in these processes and delineate possible strategies to interfere with them. Dietary interventions (eg intermittent fasting) and sirtuin‐activating compounds are among the most promising interventions shown to promote protective effects on the ageing cardiovascular system. We conclude that ageing and longevity genes modulate cardiovascular function by acting on deleterious downstream processes such as inflammation and oxidative stress, thus representing promising targets for the prevention and treatment of age‐related cardiovascular dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To obtain a real-world perspective of the optimal timing of angiography performed within 24 hours of admission with non-ST elevation myocardial infarction (NSTEMI).Background: Current guidelines recommend angiography within 24 hours of hospitalisation with NSTEMI. The recent VERDICT trial found that angiography within 12 hours of admission with NSTEMI was associated with improved cardiovascular outcomes among high-risk patients. We compared the outcomes of real-world NSTEMI patients undergoing angiography within 12 hours of admission with those of patients undergoing angiography 12 to 24 hours after admission.Methods: NSTEMI patients without life-threatening features who received angiography within 24 hours of admission were obtained from the SPUM-ACS registry, a cohort of consecutive patients admitted with acute coronary syndromes to four university hospitals in Switzerland. Cox models assessed for an association between door-to-catheter time and one-year major adverse cardiovascular events (MACE: cardiovascular mortality, myocardial infarction, and stroke).Results: Of 2672 NSTEMI patients, 1832 met the inclusion criteria. Among them, 1464 patients underwent angiography within 12 hours (12 h group) compared with 368 patients between 12 and 24 hours (12-24 h group). Multiple logistic regression identified out-of-hours admission as the only factor associated with delayed angiography. After 2 : 1 propensity score matching, 736 patients from the 12 h group and 368 patients from the 12-24 h group demonstrated no significant difference in rates of one-year MACE (7.7% vs. 7.3%, HR: 1.050, 95% CI 0.637-1.733, p=0.847). Stratification by GRACE score (>140 vs. ≤140) found no significant reduction in MACE among high-risk patients in the 12 h group (p=0.847). Stratification by GRACE score (>140 vs. ≤140) found no significant reduction in MACE among high-risk patients in the 12 h group (.Conclusions: In an unselected real-world cohort of NSTEMI patients, angiography within 12 hours of admission was not associated with improved one-year cardiovascular outcomes when compared with angiography 12 and 24 hours after admission, even among high-risk patients. [ABSTRACT FROM AUTHOR]

Objective: To determine the relative risks of cardiovascular (CV), gastrointestinal (GI), and renal adverse events during long‐term treatment with celecoxib, compared with ibuprofen and naproxen, in patients with osteoarthritis (OA) and patients with rheumatoid arthritis (RA). Methods: A total of 24,081 patients with OA or RA who had a moderate or high risk for CV disease were enrolled internationally into a double‐blind randomized controlled trial. Interventions included celecoxib at a dosage of 100–200 mg twice daily, ibuprofen at a dosage of 600–800 mg 3 times daily, or naproxen at a dosage of 375–500 mg twice daily. The main outcomes were the first occurrence of a major adverse CV event, GI event, or renal event, and mortality. Results: In the subgroup of patients with OA, the risk of a major adverse CV event was significantly reduced when celecoxib was compared with ibuprofen (hazard ratio [HR] 0.84, 95% confidence interval [95% CI] 0.72–0.99), but no significant difference was observed when celecoxib was compared with naproxen. In the RA subgroup, comparisons of celecoxib versus ibuprofen and celecoxib versus naproxen for the risk of major adverse CV events revealed HRs of 1.06 (95% CI 0.69–1.63) and 1.22 (95% CI 0.78–1.92), respectively. In the OA subgroup, comparisons of celecoxib versus ibuprofen for the risk of GI events showed an HR of 0.68 (95% CI 0.51–0.91), and a comparison of celecoxib versus naproxen showed an HR of 0.73 (95% CI 0.55–0.98). Duplicate comparisons in patients with RA revealed HRs of 0.48 (95% CI 0.22–1.07) and 0.54 (95% CI 0.24–1.24), respectively. In patients with OA, a comparison of celecoxib versus ibuprofen for the risk of renal events showed an HR of 0.58 (95% CI 0.40–0.82). In patients with RA, celecoxib treatment was associated with significantly lower mortality compared with naproxen treatment (HR 0.47, 95% CI 0.25–0.88). Conclusion: Treatment with celecoxib at approved dosages conferred a similar or lower risk of CV, GI, and renal adverse events compared with treatment with ibuprofen or naproxen in patients with OA and patients with RA. [ABSTRACT FROM AUTHOR]

Aims: Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF) and has been suggested to be associated with poor prognosis. Recently completed double-blind randomised controlled trials (RCTs) studying HF patients with ID have shown improvements in functional capacity, symptoms and quality of life when treated with i.v. ferric carboxymaltose (FCM). This individual patient data meta-analysis investigates the effect of FCM vs. placebo on recurrent hospitalisations and mortality in HF patients with ID.Methods and Results: Individual patient data were extracted from four RCTs comparing FCM with placebo in patients with systolic HF and ID. The main outcome measures were recurrent cardiovascular (CV) hospitalisations and CV mortality. Other outcomes included cause-specific hospitalisations and death. The main analyses of recurrent events were backed up by time-to-first-event analyses. In total, 839 patients, of whom 504 were randomised to FCM, were included. Compared with those taking placebo, patients on FCM had lower rates of recurrent CV hospitalisations and CV mortality [rate ratio 0.59, 95% confidence interval (CI) 0.40-0.88; P = 0.009]. Treatment with FCM also reduced recurrent HF hospitalisations and CV mortality (rate ratio 0.53, 95% CI 0.33-0.86; P = 0.011) and recurrent CV hospitalisations and all-cause mortality (rate ratio 0.60, 95% CI 0.41-0.88; P = 0.009). Time-to-first-event analyses showed similar findings, with somewhat attenuated treatment effects. The administration of i.v. FCM was not associated with an increased risk for adverse events.Conclusions: Treatment with i.v. FCM was associated with a reduction in recurrent CV hospitalisations in systolic HF patients with ID. [ABSTRACT FROM AUTHOR]

Aims: Clinical presentation of takotsubo syndrome (TTS) mimics acute coronary syndrome (ACS) and does not allow differentiation. We aimed to develop a clinical score to estimate the probability of TTS and to distinguish TTS from ACS in the acute stage.Methods and Results: Patients with TTS were recruited from the International Takotsubo Registry ( www.takotsubo-registry.com) and ACS patients from the leading hospital in Zurich. A multiple logistic regression for the presence of TTS was performed in a derivation cohort (TTS, n = 218; ACS, n = 436). The best model was selected and formed a score (InterTAK Diagnostic Score) with seven variables, and each was assigned a score value: female sex 25, emotional trigger 24, physical trigger 13, absence of ST-segment depression (except in lead aVR) 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve (AUC) for the resulting score was 0.971 [95% confidence interval (CI) 0.96-0.98] and using a cut-off value of 40 score points, sensitivity was 89% and specificity 91%. When patients with a score of ≥50 were diagnosed as TTS, nearly 95% of TTS patients were correctly diagnosed. When patients with a score ≤31 were diagnosed as ACS, ∼95% of ACS patients were diagnosed correctly. The score was subsequently validated in an independent validation cohort (TTS, n = 173; ACS, n = 226), resulting in a score AUC of 0.901 (95% CI 0.87-0.93).Conclusion: The InterTAK Diagnostic Score estimates the probability of the presence of TTS and is able to distinguish TTS from ACS with a high sensitivity and specificity.Trial Registration: NCT0194762. [ABSTRACT FROM AUTHOR]

Background: Chronic heart failure (CHF) is the final stage of many heart diseases. To improve outcomes, important risk factors for adverse clinical events in the CHF population need to be identified. The aim of the present study was to delineate the influence of long-term blood pressure (BP) changes on prognosis and mortality in a real-world cohort of CHF patients.Methods and Results: This is a retrospective longitudinal analysis. Repeated office BP measurements were scheduled during follow-up visits every 3-6 months. The primary endpoint was time to death or heart transplantation (HTx). A Cox regression with time-dependent strata was used to analyse the effect of systolic BP (SBP) values and its change during follow-up on the primary endpoint. A total of 927 patients presented with a median survival of 7.7 [95% confidence interval (CI) 6.6-9.8] years. During follow-up, 220 patients died and 70 patients underwent HTx. The BP stratum with the most stable values showed the best survival. Blood pressure changes with an increase or decrease greater than ±10 mmHg per year led to a significantly worse outcome [hazard ratio (HR) 1.8 and 2.0, respectively]. The stratum with the lowest SBP levels (<90 mmHg) had the highest mortality. Multiple regression analysis showed a HR factor of 17 (95% CI 9.7-29) in comparison with the stratum with SBP ≥130 mmHg.Conclusion: Low SBP (<90 mmHg) and pronounced long-term changes in SBP were associated with poor survival in patients with CHF. Additional prospective studies are warranted to further specify optimal BP targets in patients with CHF. [ABSTRACT FROM AUTHOR]

Low-flow low-gradient severe aortic stenosis (LFLGAS) is associated with worse outcomes. Aortic valve calcification patterns of LFLGAS as compared to non-LFLGAS have not yet been thoroughly assessed. 137 patients undergoing transcatheter aortic valve replacement (TAVR) with preprocedural multidetector computed tomography (MDCT) and postprocedural transthoracic echocardiography were enrolled. Calcification characteristics were assessed by MDCT both for the total aortic valve and separately for each leaflet. 34 patients had LFLGAS and 103 non-LFLGAS. Total aortic valve calcification volume (p<0.001), mass (p<0.001), and density (p=0.004) were lower in LFLGAS as compared to non-LFLGAS patients. At 30-day follow-up, mean transaortic pressure gradients and more than mild paravalvular regurgitation did not differ between groups. In conclusion, LFLGAS and non-LFLGAS express different calcification patterns which, however, did not impact on device success after TAVR. [ABSTRACT FROM AUTHOR]

Aims: In patients with aortic stenosis (AS), echocardiographic grading of stenosis severity is important, in particular for transcatheter aortic valve implantation (TAVI). Three-dimensional (3D) echocardiography and correction for pressure recovery (PR) by energy loss index (ELI) may improve aortic valve area (AVA) calculation. Methods and Results: Thirty-nine patients with severe AS evaluated for TAVI were included. Left ventricular outflow tract (LVOT) and ascending aorta (AA) cross-sectional area were determined in transthoracic two-dimensional echocardiography (2DTTE), 2D transesophageal echocardiography (TEE), 3DTEE, and multislice computed tomography (MSCT). AVA was calculated by the continuity equation and corrected for PR. ELI was determined as [(AVA × AA)/(AA − AVA)]/body surface area. LVOT area was 2.41 ± 0.17 cm2 calculated using 2DTTE, 2.82 ± 0.16 cm2 calculated using 2DTEE, 3.96 ± 0.14 cm2 planimetered in 3DTEE, and 4.47 ± 0.18 cm2 planimetered in MSCT (P < 0.001). AA area was 4.62 ± 0.23 cm2 calculated using 2DTTE, 4.64 ± 0.23 cm2 calculated using 2DTEE, 5.35 ± 0.25 cm2 planimetered in 3DTEE, and 6.56 ± 0.31 cm2 planimetered in MSCT (P < 0.001). Indexed aortic valve area (AVAI) calculated by 2DTTE and 2DTEE was smaller (0.27 ± 0.02 cm2/m2 and 0.32 ± 0.02 cm2/m2) compared to 3DTEE (0.45 ± 0.02 cm2/m2; P < 0.001). When AVAI determined by 3DTEE was corrected for PR by calculation of ELI, there was a further increase (0.52 ± 0.03 cm2/m2; P < 0.001), and 10/36 (27.8%) patients were reclassified to moderate AS. Conclusion: Three-dimensional TEE is more accurate than 2DTTE and 2DTEE for determining LVOT and AA dimensions. When AS severity is determined by 3DTEE and corrected for PR using the 3D values, it needs to be reclassified from severe to moderate in almost a third of patients. [ABSTRACT FROM AUTHOR]

Objectives It remains still unclear whether the use of modern noninvasive diagnostic modalities for evaluation of coronary artery disease (computed tomography coronary angiography (CTCA), nuclear myocardial perfusion imaging (MPI)) were able to change the 'diagnostic yield' of invasive coronary angiography (ICA). Methods The total number of ICA in the years 2000-2009 was related to the number of percutaneous interventions (PCIs) and we assessed whether there was a significant trend over time using time series analyses. We compared these data with the number of patients undergoing CTCA and nuclear MPI in the same time period. Results During the 10-year observational period, 23,397 ICA were performed. The proportion of purely diagnostic ICA (without PCI) remained stable over the whole study period (tau = −0.111, P = 0.721). A CTCA program was initiated in 2005 and 1,407 examinations were performed until 2009. Similarly, the number of nuclear MPI increased from 2,284 in the years 2000-2004 to 5,260 in the years 2005-2009 (P = 0.009). Conclusion Despite increasing availability, noninvasive testing modalities did not significantly alter the rate of purely diagnostic ICA, and still are underused as gatekeeper to ICA. Further effort is needed to optimize the use of noninvasive imaging modalities in the work-up process for coronary artery disease. (J Interven Cardiol 2014;27:50-57) [ABSTRACT FROM AUTHOR]

Aims Therapy with i.v. iron in patients with chronic heart failure (CHF) and iron deficiency (ID) improves symptoms, functional capacity, and quality of life. We sought to investigate whether these beneficial outcomes are independent of anaemia. Methods and results FAIR-HF randomized 459 patients with CHF [NYHA class II or III, LVEF ≤40% (NYHA II) or ≤45% (NYHA III)] and ID to i.v. iron as ferric carboxymaltose (FCM) or placebo in a 2:1 ratio. We analysed the efficacy and safety according to the presence or absence of anaemia (haemoglobin ≤120 g/L) at baseline. Of 459 patients, 232 had anaemia at baseline (51%). The effect of FCM on the primary endpoints of self-reported Patient Global Assessment (PGA) and NYHA class at week 24 was similar in patients with and without anaemia [odds ratio (OR) for improvement, 2.48 vs. 2.60, P = 0.97 for PGA and 1.90 vs. 3.39, P = 0.51 for NYHA). Results were also similar for the secondary endpoints, including PGA and NYHA at weeks 4 and 12, 6 min walk test distance, Kansas City Cardiomyopathy Questionnaire overall score, and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points. Regarding safety, no differences were noticed in the rates of death or first hospitalization between FCM and placebo both in anaemic and in non-anaemic patients. Conclusions Treatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia. Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered. [ABSTRACT FROM AUTHOR]

SUMMARY Objectives: The strong inverse relationship between plasma high-density lipoprotein (HDL)-cholesterol and atherosclerotic cardiovascular disease provides the epidemiological basis that HDL is atheroprotective. Since HDL enhances cholesterol efflux and exhibits potent antiinflammatory properties, the aim of the present study was to investigate whether infusion of reconstituted HDL (rHDL) impacts on vascular function, a well-established surrogate of atherosclerotic vascular disease, as well as markers of inflammation and oxidative stress in patients with acute coronary syndromes (ACS). Methods: Twenty-nine patients with ACS were randomized to double-blind treatment with rHDL or albumin. Endothelium-dependent and independent vasodilatation to intraarterial acetylcholine and sodium nitroprusside were measured by forearm venous occlusion plethysmography. In addition, oxidized LDL and high-sensitivity C-reactive protein were determined as markers of oxidative stress and vascular inflammation. Results: rHDL infusion increased plasma HDL ( P < 0.0001) and decreased LDL ( P < 0.0001). Oxidized LDL ( P= 0.11), high-sensitivity C-reactive protein ( P= 0.12) and the response to endothelium-dependent and -independent vasodilatators remained unchanged after rHDL compared to albumin infusion (14.9 ± 9.2 versus 14.5 ± 12.4, P= 0.93 and 12.8 ± 7.1 versus 13.2 ± 9.6, P= 0.27, respectively). Conclusions: An increase of HDL and a reduction of LDL notwithstanding, human rHDL did not improve vascular function in patients with ACS thus further challenging the clinical benefit of interventions, which rapidly raise HDL in ACS, particularly with the infusion of reconstituted HDL. [ABSTRACT FROM AUTHOR]

Interactions between peripheral blood mononuclear cells (PBMC) and the endothelium critically determine vascular repair and reparative angiogenesis, but also pathological processes, such as atherosclerosis. Current methodology to study these interactions mostly regards PBMC as a homogenous population or it restricts its focus on individual cell types and therefore does not appreciate the differential behavior of individual PBMC subpopulations, which synergize or antagonize each other to obtain the overall effect. We therefore developed a flow cytometry-based in vitro assay to assess multiple parameters of interaction between several individual populations of PBMC and an endothelial monolayer. Freshly isolated, unlabelled human PBMC were left to adhere to or transmigrate through a monolayer of fluorescence-labeled human aortic endothelial cells grown to confluence on the filter membrane of sterile transwell migration inserts. Monocyte chemoattractant protein-1 (MCP-1) was applied as a chemoattractant to the lower compartment of the migration chamber. After 6 h, transmigrating PBMC were harvested from the lower compartment, while nonadherent and adhering cell populations were harvested from the upper compartment by sequential washing/detachment. All three cell fractions were then individually stained with fluorescence-labeled monoclonal antibodies and analyzed by flow cytometry. Quantification was achieved by the usage of counting beads. Endothelial cells were separated from PBMC during the analysis by a multiparametric gating strategy. Using the newly established assay, we observed distinct migration patterns for inflammatory CD14hiCD16neg and resident CD16pos monocytes. These cell types differed in their basal adhesion and transmigration patterns as well as their responses to the CCR2 ligand MCP-1. This assay allows for the parallel study of interactions between multiple individual leukocyte populations and an endothelial layer. Several readouts can be derived from the same experiment, like the composition of adhering and transmigrating cell fractions or the individual adhesion/migration behavior of several distinct cell types. © 2011 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Chronic right ventricular apical (RVA) pacing has been associated with increased risk of heart failure and adverse outcome. The acute effects of RVA pacing on three-dimensional (3D) ventricular function and mechanical dyssynchrony are not well known. We performed a real-time 3D echocardiographic (RT3DE) study to assess global and regional left ventricular function during RVA pacing. Twenty-six patients with implanted cardiac devices and normal intrinsic atrioventricular conduction were included in the study. RT3DE was performed during intrinsic sinus rhythm and during RVA pacing. Quantification of global and regional left ventricular function was performed offline by time-volume analysis of 16 myocardial segments. Time to reach minimum regional volume was calculated for each segment as a percentage of the cardiac cycle. The systolic dyssynchrony index (SDI) was defined as the standard deviation of these time periods. Longitudinal function was assessed by time-volume analysis of apical, midventricular, and basal segments. During RVA pacing, a reversed apical-to-basal longitudinal contraction sequence was observed in 58% of all patients. RVA pacing was associated with increased left ventricular (LV) dyssynchrony (SDI increase from 4.4 ± 2.2% to 6.3 ± 2.4%, P = 0.001) and reduced LV ejection fraction (decrease from 53 ± 13% to 47 ± 14%, P = 0.05). RT3DE assessment of LV function provides evidence that pacing from the RVA results in acute alterations in LV contraction sequence and increased LV dyssynchrony. Further studies are warranted to assess the potential of RT3DE to identify patients who might be at increased risk of pacing-induced heart failure or who might benefit from alternate-site or multisite pacing. (PACE 2011; 76-81) [ABSTRACT FROM AUTHOR]

An “unhealthy” diet is considered as a main cause of increased atherosclerotic cardiovascular disease in the industrialized countries. There is a substantial interest in the potential cardiovascular protective effects of “nutraceuticals,” that is food-derived substances that exert beneficial health effects. The correct understanding of cardiovascular effects of these compounds will have important implications for cardiovascular prevention strategies. Endothelial dysfunction is thought to play an important role in development and progression of atherosclerosis, and the characterization of the endothelial effects of several nutraceuticals may provide important insights into their potential role in cardiovascular prevention. At the same time, the analysis of the endothelial effects of nutraceuticals may also provide valuable insights into mechanisms of why certain nutraceuticals may not be effective in cardiovascular prevention, and it may aid in the identification of food-derived substances that may have detrimental cardiovascular effects. These findings further support the notion that nutraceuticals do need support from large clinical outcome trials with respect to their efficacy and safety profile for cardiovascular prevention, before their widespread use can be recommended. In fact, the term nutraceutical was coined to encourage an extensive and profound research activity in this field, and numerous large-scale clinical outcome trials to examine the effects of nutraceuticals on cardiovascular events have now been performed or are still ongoing. Whereas it is possible that single nutraceuticals may be effective in cardiovascular prevention, this field of research provides also valuable insights into which food components may be particularly important for cardiovascular prevention, to further advice the composition of a particularly healthy diet. The present review summarizes recent studies on the endothelial effects of several nutraceuticals, that have been intensely studied. [ABSTRACT FROM AUTHOR]

Introduction. For pulmonary vein isolation in patients with atrial fibrillation (AF), some centers use the double transseptal puncture technique for catheter access in order to facilitate catheter manipulation within the left atrium. However, no safety data has so far been published using this approach. Method. 269 ablation procedures were performed in 243 patients (mean age 56.6 ± 9.3 years, 75% men) using the double transseptal puncture for catheter access in all cases. Patients were considered for ablation of paroxysmal (80%), persistent (19%), and permanent (1%) AF. 230 procedures were performed on an outpatient basis (85.5%), and 26 were repeat procedures (9.7%). Results. The double transseptal puncture catheter access was successfully achieved in all patients. The procedural success with the endpoint of pulmonary vein isolation was reached in 255 procedures (95%). A total of 1048 out of 1062 pulmonary veins (99%) were successfully isolated. Major complications occurred in eight patients (3.0%). Of these, seven patients (2.6%) had pericardial effusion requiring percutaneous drainage, and one patient (0.4%) suffered a minor reversible stroke. One patient (0.4%) had a minor air embolism with transient symptoms. Conclusion. The double transseptal puncture catheterization technique allows easy catheter manipulation within the left atrium to reach the goal of acute procedural success in AF ablation. Procedure-related complications are rare, and the technique can be used safely for AF ablation in the outpatient setting. [ABSTRACT FROM AUTHOR]

Aims: Iron deficiency (ID) and anaemia are common in patients with chronic heart failure (CHF). The presence of anaemia is associated with increased morbidity and mortality in CHF, and ID is a major reason for the development of anaemia. Preliminary studies using intravenous (i.v.) iron supplementation alone in patients with CHF and ID have shown improvements in symptom status. FAIR-HF (Clinical Trials.gov NCT00520780) was designed to determine the effect of i.v. iron repletion therapy using ferric carboxymaltose on self-reported patient global assessment (PGA) and New York Heart Association (NYHA) in patients with CHF and ID.Methods and Results: This is a multi-centre, randomized, double-blind, placebo-controlled study recruiting ambulatory patients with symptomatic CHF with LVEF < or = 40% (NYHA II) or < or =45% (NYHA III), ID [ferritin <100 ng/mL or ferritin 100-300 ng/mL when transferrin saturation (TSAT) < 20%], and haemoglobin 9.5-13.5 g/dL. Patients were randomized in a 2:1 ratio to receive ferric carboxymaltose (Ferinject((R))) 200 mg iron i.v. or saline i.v. weekly until iron repletion (correction phase), then monthly until Week 24 (maintenance phase). Primary endpoints are (i) self-reported PGA at Week 24 and (ii) NYHA class at Week 24, adjusted for baseline NYHA class.Conclusion: This study will provide evidence on the efficacy and safety of iron repletion with ferric carboxymaltose in CHF patients with ID with and without anaemia. [ABSTRACT FROM AUTHOR]

ABSTRACT Nebivolol is a racemic mixture of d- and 1-enantiomers. The drug is characterized by β1-adrenoceptor selectivity and long-acting β1-blockade exerted predominantly by d-enantiomer. Nebivolol is devoid of intrinsic sympathomimetic activity and has no relevant membrane stabilizing action. Antiproliferative properties of nebivolol were demonstrated in endothelial and smooth muscle cell cultures. Infusion of nebivolol causes a vasodilation in all vascular beds by endothelial-dependent mechanism involving stimulation of β3-adrenoceptors as well as by endothelial-independent mechanism. Nebivolol possesses not only direct vasodilator properties but also augments the action of endothelium-dependent vasodilators. The antioxidant property of nebivolol can at least in part explain why treatment with this drug enhances eNOS activity and minimizes the reperfusion-induced myocardial injury. The systemic effects of nebivolol in humans have an unusual hemodynamic profile. In contrast to traditional β-adrenoceptor antagonists, nebivolol reduces preload and afterload due to systemic vasodilation and improves arterial distensibility. At 5 mg daily nebivolol effectively reduces systolic and diastolic blood pressure over a 24-h period. During treatment with nebivolol arterial pressure follows the natural circadian rhythm. Trough-to-peak ratio for nebivolol is 0.9. It has been demonstrated in numerous placebo-controlled studies that exercise tolerance is not reduced during nebivolol therapy. By chronic administration to patients with left ventricular dysfunction nebivolol increases myocardial contractility. Nebivolol produced no significant changes in lipid levels, insulin sensitivity or glucose tolerance. These findings make nebivolol a promising therapeutic tool for the treatment of arterial hypertension and chronic heart failure. [ABSTRACT FROM AUTHOR]

The "Intracardiac Electrogram (EGM) Width Criterion," the first digital signal processing feature used in an implantable cardioverter defibrillator (ICD), is a detection enhancement algorithm that intends to improve ventricular tachycardia (VT) detection specificity by rejecting inappropriately detected supraventricular tachyarrhythmias. The algorithm may be activated after setting the optimal EGM source, slew, and width thresholds based on EGM width testing during sinus rhythm. This study evaluates the accuracy of the EGM width measurements during exercise testing. Twenty-one patients with Medtronic Micro Jewel II Model 7223 ICDs underwent treadmill exercise testing. EGM width testing was repeatedly performed during exercise and recovery to detect potential inappropriate measurements. In seven (33%) patients the EGM Width Criterion inappropriately confirmed VT detection. Eleven patients had inappropriately wide EGM width measurements, but did not satisfy the EGM Width Criterion. The causes of wide EGM width measurements were an actual increase in EGM width and/or inappropriate detection of the baseline irregularities as EGM onset or offset points. Based on our observations, we recommend to test the EGM Width Criterion during exercise testing for optimal ICD programming. [ABSTRACT FROM AUTHOR]