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Aims Incident atrial fibrillation (AF) is an adverse prognostic indicator in heart failure (HF); identifying modifiable targets may be relevant to reduce the incidence and morbidity of AF. Therefore, we examined the association between quality of HF care and risk of AF. Methods and results Using the Danish Heart Failure Registry, we conducted a nationwide registry-based cohort study of all incident HF patients diagnosed between 2008 and 2018 and without history of AF. Quality of HF care was assessed by seven process performance measures, including echocardiographic examination, New York Heart Association classification, treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid antagonists, physical training, and patient education. In the main analysis, we examined adherence with all measures in a cohort of 25 100 patients (mean age 68.5 ± 13.2 years; 33.6% women). The median follow-up was 3.1 years. Cox proportional hazard regressions estimated the hazard ratios (HRs) with 95% confidence intervals (95% CIs) between the number of fulfilled measures and incident AF. In a multivariable-adjusted analysis with 0 fulfilled performance measures as reference, the HRs (95% CIs) were 1: 0.78 (0.61–1.00), 2: 0.63 (0.49–0.80), 3: 0.53 (0.36–0.80), 4: 0.64 (0.44–0.94), 5: 0.56 (0.39–0.82), 6: 0.51 (0.35–0.74), and 7: 0.49 (0.33–0.73), with a significant decreasing linear trend (P Conclusion In patients with incident HF, fulfilment of guideline-based process performance measures was associated with decreased long-term risk of AF. This study supports initiatives to improve the quality of care for patients with HF to prevent incident AF.

Background: Data on the association between quality of heart failure (HF) care and outcomes among patients with incident HF are sparse. We examined the association between process performance measures and clinical outcomes in patients with incident HF with reduced ejection fraction. Methods: Patients with incident HF with reduced ejection fraction (n=10 966) between January 2008 and October 2015 were identified from the Danish HF Registry. Data from public registries were linked. Multivariable regression analyses were used to assess the association between 6 guideline-recommended HF care processes (New York Heart Association assessment, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, exercise training, and patient education) and all-cause and HF readmission, all-cause and HF hospital days, and mortality within 3 to 12 months after HF diagnosis. The associations were analyzed according to the percentages of all relevant performance measures fulfilled for the individual patient (0%–50% [reference group], >50%–75%, and >75%–100%) and for the individual performance measures. Results: Fulfilling >75% to 100% of the performance measures (n=5341 [48.7%]) was associated with lower risk of all-cause readmission (adjusted hazard ratio, 0.78 [95% CI, 0.68–0.89]) and HF readmission (adjusted hazard ratio, 0.71 [95% CI, 0.54–0.92]), lower use of all-cause hospital days (adjusted mean ratio, 0.73 [95% CI, 0.70–0.76]) and HF hospital days (adjusted mean ratio, 0.79 [95% CI, 0.70–0.89]), and lower mortality (adjusted hazard ratio, 0.42 [95% CI, 0.32–0.53]). A dose-response relationship was observed between fulfilling more performance measures and mortality (adjusted hazard ratio, 0.62 [95% CI, 0.49–0.77] fulfilling >50%–75% of the measures). Fulfilling individual performance measures, except mineralocorticoid receptor antagonist therapy, was associated with lower adjusted all-cause readmission, lower adjusted use of all-cause and HF hospital days, and lower adjusted mortality. Conclusions: Fulfilling more process performance measures was associated with better clinical outcomes in patients with incident HF with reduced ejection fraction.

ObjectiveWe examined temporal heart failure (HF) prescription patterns in a large representative sample of real-world patients in the UK, using electronic health records (EHR).MethodsFrom primary and secondary care EHR, we identified 85 732 patients with a HF diagnosis between 2002 and 2015. Almost 50% of patients with HF were women and the median age was 79.1 (IQR 70.2–85.7) years, with age at diagnosis increasing over time.ResultsWe found several trends in pharmacological HF management, including increased beta blocker prescriptions over time (29% in 2002–2005 and 54% in 2013–2015), which was not observed for mineralocorticoid receptor-antagonists (MR-antagonists) (18% in 2002–2005 and 18% in 2013–2015); higher prescription rates of loop diuretics in women and elderly patients together with lower prescription rates of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, beta blockers or MR-antagonists in these patients; little change in medication prescription rates occurred after 6 months of HF diagnosis and, finally, patients hospitalised for HF who had no recorded follow-up in primary care had considerably lower prescription rates compared with patients with a HF diagnosis in primary care with or without HF hospitalisation.ConclusionIn the general population, the use of MR-antagonists for HF remained low and did not change throughout 13 years of follow-up. For most patients, few changes were seen in pharmacological management of HF in the 6 months following diagnosis.

Aims: Pharmacological therapies for heart failure (HF) aim to improve congestion, symptoms, and prognosis. Failing to take medication is a potential cause of worsening HF. Characterizing the effects of short-term medication omission could inform the development of better technologies and strategies to detect and interpret the reasons for worsening HF. We examined the effect of planned HF medication omission for 48 h on weight, echocardiograms, transthoracic bio-impedance, and plasma concentrations of NT-proBNP. Methods and results: Outpatients with stable HF and an LVEF

BACKGROUND: Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously.METHODS: In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (RESULTS: The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P = 0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-cardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively.CONCLUSIONS: In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.).

Aims: To examine the association between fulfilment of performance measures supported by clinical guidelines recommendations and 1-year mortality among patients with incident heart failure (HF) in Denmark.Methods and results: A nationwide population-based follow-up study based on the Danish Heart Failure Registry. All Danish hospital departments caring for patients with HF. We identified 24,308 in-and outpatients diagnosed with HF from 2003 to 2010. Quality of care was defined as receiving the guideline recommended processes of care: use of echocardiography, New-York-Heart-Association -classification, treatment with angiotensin-converting-enzyme inhibitors/angiotensin-II-receptor blocker, betablockers, physical training and patient education.Main outcome measure: 1-year mortality. We used multiple imputation and multivariable Cox Proportional Hazard Regression to compute Hazard Ratios (HRs) for 1-year mortality adjusted for potential confounding factors. Within 1 year, 17.1% of the patients died and the adjusted HRs ranged from 0.61 (95% Confidence Interval ((CI) 0.55-0.67)) for patient education to 0.99 (95% CI 0.90-1.10) for betablocker therapy. The association between meeting more performance measures and 1-year mortality appeared to follow a dose-response pattern: Using 0-25% of fulfilled measures as reference, patients who fulfilled 76- 100% of the performance measures had an adjusted HR of 0.43 (95% CI 0.38-0.48), while the adjusted HR was 0.96 (95% CI 0.86-1.07) for patients who fulfilled between 26-50% of the performance measures.Conclusion: Meeting process performance measures, which reflect care in concordance with clinical guideline recommendations, was associated with substantially lower 1-year mortality among patients with incident HF.

OBJECTIVES: Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on β-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature. METHODS: In 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins. RESULTS: In adjusted analyses, HF1, HF2 and CKD273 (p ≤ 0.024) were higher in BB users than non-users with a similar trend for ACSP75 (p = 0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (p ≥ 0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (p ≤ 0.014). There were no differences in the urinary biomarkers (p ≥ 0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments. CONCLUSIONS: BB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial. ispartof: PLOS ONE vol:13 issue:9 ispartof: location:United States status: published

In patients with bicuspid aortic valve (BAV), beta-blockers (BB) are assumed to slow ascending aorta (AAo) dilation by reducing wall shear stress (WSS) on the aneurysmal segment. The aim of this study was to assess differences in AAo peak velocity and WSS in BAV patients with and without BB therapy. BAV patients receiving BB (BB+, n = 30, age: 47 +/- A 11 years) or not on BB (BB-, n = 30, age: 46 +/- A 13 years) and healthy controls (n = 15, age: 43 +/- A 11 years) underwent 4D flow MRI for the assessment of in vivo aortic 3D blood flow. Peak systolic velocities and 3D WSS were calculated at the anterior and posterior walls of the AAo. Both patient groups had higher maximum and mean WSS relative to the control group (p = 0.001 to p = 0.04). WSS was not reduced in the BB+ group compared to BB- patients in the anterior AAo (maximum: 1.49 +/- A 0.47 vs. 1.38 +/- A 0.49 N/m(2), p = 0.99, mean: 0.76 +/- A 0.2 vs. 0.74 +/- A 0.18 N/m(2), p = 1.00) or posterior AAo (maximum: 1.45 +/- A 0.42 vs. 1.39 +/- A 0.58 N/m(2), p = 1.00; mean: 0.65 +/- A 0.16 vs. 0.63 +/- A 0.16 N/m(2), p = 1.00). AAo peak velocity was elevated in patients compared to controls (p

BACKGROUND: Myriad reports suggest that frequently used prescription drugs alter the viability of breast cancer cells in pre-clinical studies. Routine use of these drugs, therefore, may impact breast cancer prognosis, and could have important implications for public health.METHODS: The Danish Breast Cancer Group (DBCG) clinical database provides high-quality prospectively collected data on breast cancer diagnosis, treatment, and routine follow-up for breast cancer recurrence. Individual-level linkage of DBCG data to other population-based and medical registries in Denmark, including the Danish National Prescription Registry, has facilitated large population-based pharmacoepidemiology studies. A unique advantage of using DBCG data for such studies is the ability to investigate the association of drugs with breast cancer recurrence rather than breast cancer mortality - which may be misclassified - or all-cause mortality. Here we summarize findings from pharmacoepidemiological studies, based on DBCG data, on the association between routinely used prescription drugs and risk of breast cancer recurrence.RESULTS: Our findings suggest that concurrent use of glucocorticoids, ACE inhibitors, aspirin, NSAIDs, selective COX-2 inhibitors, digoxin, and opioids has little impact on breast cancer recurrence. Similarly, patients who use SSRIs concurrently with tamoxifen treatment are not at increased risk of recurrence. In contrast, post-diagnostic use of simvastatin, a lipophilic statin, correlates with a decreased risk of breast cancer recurrence, providing a rationale for a prospective randomized clinical trial investigating simvastatin as an adjuvant therapy for breast cancer.CONCLUSION: As a whole, findings of pharmacoepidemiological studies based on DBCG data provide reassurance to physicians and healthcare personnel who provide supportive care during and after cancer (including prescriptions for comedications) and to breast cancer survivors for whom the risk of breast cancer recurrence is a major concern.

Aims:\ud \ud Pharmacological therapies for heart failure (HF) aim to improve congestion, symptoms, and prognosis. Failing to take medication is a potential cause of worsening HF. Characterizing the effects of short-term medication omission could inform the development of better technologies and strategies to detect and interpret the reasons for worsening HF. We examined the effect of planned HF medication omission for 48 h on weight, echocardiograms, transthoracic bio-impedance, and plasma concentrations of NT-proBNP.\ud Methods and results:\ud \ud Outpatients with stable HF and an LVEF

Objective. To determine the risk in administering β-blockers, contrast-induced nephropathy (CIN) and the trend in X-ray use, during coronary computed tomography angiography (CCTA). Methods. A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60 beats per minute, oral and/or intravenous β-blockers were administered. Using questionnaires, information on the adverse effects of β-blockers was collected from the patients. The levels of s-creatinine and estimated GFR (eGFR) were measured before and after contrast enhanced CCTA. Radiation exposure was compared with the exposure 3 years earlier. Results. There was no significant difference in the symptoms (dizziness, lipothymia and palpitations) between patients with and patients without β-blocker pretreatment. Compared to baseline values, the decrease in s-creatinine was not significant (75.2 vs. 74.6 μmol/L, p = 0.09), while the increase in eGFR was not significant (78 vs. 79 mL/min, p = 0.17). Also, subgroups of patients with hypertension, hypercholesterolemia, diabetes or pre-existing slight impairment in renal function did not develop CIN. The mean radiation exposure decreased from 17.5 to 6.7 mSv, p < 0.0001. Conclusions. In terms of the side effects of β-blockers and contrast media, there were no short term complications to CCTA. Furthermore, the radiation dose has been dramatically diminished over the last three years.

Aim: To describe the prevalence of hypertension in care home residents, its treatment, change in treatment over time, and the achievement of blood pressure (BP) control. Method: The PubMed, Cochrane, Embase, and PsychINFO databases were searched for observational studies involving care home residents with a diagnosis of hypertension. The search was limited to English language articles involving adults and humans published from 1990 onward. Abstracts and titles were reviewed with eligible articles read in full. Bibliographies were examined for further relevant studies. The final selection of studies was then analyzed and appraised. Results: Sixteen articles were identified for analysis, of which half were studies carried out in the United States. The prevalence of hypertension in care home residents was 35% (range 16%e71%); 72% of these were on at least 1 antihypertensive (mean 1.5 antihypertensives per individual), with diuretics being the most common. The prevalence of hypertension in study populations was greater in more recent studies (P ¼ .004). ACEi/ARBs (P ¼ .001) and b-blockers (P ¼ .04) were prescribed more frequently in recent studies, whereas use of calcium-channel blockers and diuretics remained unchanged over time. The number of antihypertensives prescribed per patient was higher (correlation 0.332, P ¼ .009), whereas fewer patients achieved target BP (correlation 0.671, P ¼ .099) in more recent studies. Conclusion: Hypertension is common in care home residents and is commonly treated with antihypertensive drugs, which were prescribed more frequently in more recent studies but with no better BP control. These studies indicate a tendency toward increasing polypharmacy over time, with associated risk of adverse events, without demonstrable benefit in terms of BP control. Copyright 2014 - American Medical Directors

To investigate the association of antihypertensive medications with optic disc structure by blood pressure (BP) level, in nonglaucoma subjects.Cross-sectional, population-based study.A subset of Thessaloniki Eye Study participants was included in this study. Subjects were interviewed for medical history and underwent extensive ophthalmic examination, BP measurement, and optic disc imaging with the Heidelberg retinal tomograph. Subjects treated for hypertension were grouped in the following groups: (1) angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers; (2) beta blockers and/or calcium-channel blockers; (3) diuretics alone or combined with others; and (4) other combinations. Cup size and cup-to-disc (C/D) ratio in the above groups were compared with the untreated group, using regression models. Analyses were rerun for subjects with systolic BP (SBP)140 mm Hg, SBP≥140 mm Hg, diastolic BP (DBP)90 mm Hg, and DBP≥90 mm Hg.Among 232 subjects, 131 were receiving antihypertensive medications. In subjects with DBP90 mm Hg, all medications groups were associated with larger cup size and higher C/D ratio compared with the untreated group. Results were similar in subjects with SBP140 mm Hg, with the exception of the beta blockers and/or calcium-channel blockers group. None of the medications groups were associated with the Heidelberg retinal tomograph parameters in those with DBP≥90 mm Hg or SBP≥140 mm Hg.All classes of antihypertensive medications were associated with larger cup size and higher C/D ratio in subjects with either DBP90 mm Hg or SBP140 mm Hg. These results suggest that there is no specific medication-related effect on optic disc structure, and the associations found are mediated through the hypotensive effect of antihypertensive medications.

The safety of nonselective β-blockers (NSBBs) in advanced cirrhosis has been questioned. We used data from three satavaptan trials to examine whether NSBBs increase mortality in cirrhosis patients with ascites. The trials were conducted in 2006-2008 and included 1198 cirrhosis patients with ascites followed for 1 year. We used Cox regression to compare all-cause mortality and cirrhosis-related mortality between patients who did and those who did not use NSBBs at randomization, controlling for age, gender, Model for End-Stage Liver Disease score, Child-Pugh score, serum sodium, previous variceal bleeding, cirrhosis etiology, and ascites severity. Moreover, we identified clinical events predicting that a patient would stop NSBB treatment. At randomization, the 559 NSBB users were more likely than the 629 nonusers to have a history of variceal bleeding but less likely to have Child-Pugh class C cirrhosis, hyponatremia, or refractory ascites. The 52-week cumulative all-cause mortality was similar in the NSBB user and nonuser groups (23.2% versus 25.3%, adjusted hazard ratio = 0.92, 95% confidence interval 0.72-1.18), and NSBBs also did not increase mortality in the subgroup of patients with refractory ascites (588 patients, adjusted hazard ratio = 1.02, 95% confidence interval 0.74-1.40) or in any other subgroup. Similarly, NSBBs did not increase cirrhosis-related mortality (adjusted hazard ratio = 1.00, 95% confidence interval 0.76-1.31). During follow-up, 29% of initial NSBB users stopped taking NSBBs, and the decision to stop NSBB treatment marked a sharp rise in mortality and coincided with hospitalization, variceal bleeding, bacterial infection, and/or development of hepatorenal syndrome. Conclusion: This large and detailed data set on worldwide nonprotocol use of NSBBs in cirrhosis patients with ascites shows that NSBBs did not increase mortality; the decision to stop NSBB treatment in relation to stressful events may have added to the safety. (Hepatology 2016;63:1968-1976).

SummaryPlaque rupture and subsequent thrombotic occlusion of the coronary artery account for as many as three quarters of myocardial infarctions. The concept of plaque stabilisation emerged about 20 years ago to explain the discrepancy between the reduction of cardiovascular events in patients receiving lipid lowering therapy and the small decrease seen in angiographic evaluation of atherosclerosis. Since then, the concept of a vulnerable plaque has received a lot of attention in basic and clinical research leading to a better understanding of the pathophysiology of the vulnerable plaque and acute coronary syndromes. From pathological and clinical observations, plaques that have recently ruptured have thin fibrous caps, large lipid cores, exhibit outward remodelling and invasion by vasa vasorum. Ruptured plaques are also focally inflamed and this may be a common denominator of the other pathological features. Plaques with similar characteristics, but which have not yet ruptured, are believed to be vulnerable to rupture. Experimental studies strongly support the validity of anti-inflammatory approaches to promote plaque stability. Unfortunately, reliable non-invasive methods for imaging and detection of such plaques are not yet readily available. There is a strong biological basis and supportive clinical evidence that low-density lipoprotein lowering with statins is useful for the stabilisation of vulnerable plaques. There is also some clinical evidence for the usefulness of antiplatelet agents, beta blockers and renin-angiotensin-aldosterone system inhibitors for plaque stabilisation. Determining the causes of plaque rupture and designing diagnostics and interventions to prevent them are urgent priorities for current basic and clinical research in cardiovascular area.

Objectives. The objective of our study was to assess hospital variations in the quality of care delivered to acute myocardial inf- arction (AMI) patients among three Swiss academic medical centres. Design. Cross-sectional study. Setting. Three Swiss university hospitals. Study participants. We selected 1129 eligible patients discharged from these hospitals from 1 January to 31 December 1999, with a primary or secondary diagnosis code (International Classification of Diseases, 10th revision (ICD-10)) of AMI. We abstracted medical records for information on demographic characteristics, risk factors, symptoms, and findings at admission. We also recorded the main ECG and laboratory findings, as well as hospital and discharge management and treatment. We excluded patients transferred to another hospital and who did not meet the clinical definition of AMI. Main outcome measures. Percentage of patients receiving appropriate intervention as defined by six quality of care indicators derived from clinical practical guidelines. Results. Among 577 eligible patients with AMI in this study, the mean (SD) age was 68.2 (13.9), and 65% were male. In the assessment of the quality indicators we excluded patients who were not eligible for the procedure. Among cohorts of 'ideal can- didates' for specific interventions, 64% in hospital A and 73% in hospital C had reperfusion within 12 hours either with throm- bolytics or percutaneous transluminal coronary angioplasty (P = 0.367). Further, in hospitals A, B, and C, respectively 97, 94, and 84% were prescribed aspirin during the initial hospitalization (P = 0.0002), and respectively 68, 91, and 75% received angio- tensin converting enzyme inhibitors at discharge in the case of left ventricular systolic dysfunction (P = 0.003). Conclusions. Our results showed important hospital-to-hospital variations in the quality of care provided to patients with AMI between these three university hospitals.

Hypertension is associated with reduced coronary vasodilatory capacity, possibly caused by structural changes in the coronary resistance vessels. Because vasodilatory treatment may correct abnormal structure better than nonvasodilating treatment, we compared whether long-term angiotensin-converting enzyme (ACE) inhibition has a greater effect on coronary reserve and cardiovascular structure than β-blockade in patients with essential hypertension. Thirty previously untreated hypertensive patients were randomized in a double-blind design to treatment for 1 year with either perindopril (4 to 8 mg per day, n=15) or atenolol (50 to 100 mg per day, n=15) and furthermore compared with normotensive controls. Cardiac output and left ventricular mass were measured with echocardiography and resistance artery structure was determined in vitro. Using positron emission tomography, myocardial perfusion (MP) was determined at rest and during dipyridamole-induced hyperemia while still on medication. Perindopril reduced left ventricular mass by 14±4% ( P P P P P P =NS), but reduced by atenolol (−32±5%, P P

Current clinical guidelines state that only beta-blockers, diuretics, calcium channel antagonists and ACE inhibitors should be used for initial pharmacotherapy for uncomplicated hypertension. On basis of experience, efficacy and costs beta-blockers and diuretics are first choice. However, the importance of the renin-angiotensin-aldosterone-system in the pathophysiology of hypertensive end-organ damage is increasingly recognised nowadays, and modulation of this system may therefore exert favourable effects on cardiovascular and cerebrovascular complications. In the LIFE study, a recently published double-blinded, randomised trial, the angiotensin-II receptor (A-II) antagonist losartan was compared with the beta-blocker atenolol in patients with essential hypertension and left ventricular hypertrophy (LVH). Patients randomised to the A-II antagonist suffered statistically significantly fewer clinical end-points, specifically fewer cerebrovascular accidents, whereas both treatments resulted in a similar decrease in blood pressure. In the subset of diabetic patients, the use of the A-II antagonist yielded an even more favourable outcome. In our opinion, it should now also be permitted to prescribe A-II antagonists as initial pharmacotherapy for patients with uncomplicated essential hypertension. It might be considered to prescribe A-II antagonists as preferred treatment for patients with essential hypertension and known LVH, especially in diabetic patients.

International audience; BACKGROUND: We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy. METHODS: In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years. RESULTS: The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P\textless0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P\textless0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years. CONCLUSIONS: In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

Essential hypertension appears to be more prevalent among blacks than among whites and has an earlier onset in blacks. Many data in this field come from studies in the African-American population. Hypertension-related complications, e.g. ischaemic heart disease, (end stage) renal failure and cerebrovascular disease, are encountered more often among blacks and frequently run a more severe course. Factors that might explain the racial difference in prevalence of hypertension and hypertensive complications include both genetic and environmental variables. Hypertension in blacks is characterized by salt sensitivity, a tendency towards expanded plasma volume and low plasma renin levels. Socioeconomic factors, the higher prevalence of obesity and insulin resistance may contribute to the high prevalence of hypertension in blacks. Aggressive antihypertensive therapy appears mandatory in the black hypertensive, possibly with lower goal blood pressures than the 140/90 mmHg generally recommended. Diuretic monotherapy proves to be the first-line therapy, calcium channel blockers are an attractive alternative. Black patients are frequently less responsive to monotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta-blocking agents. This black/white difference in therapeutic response can, however, be eliminated by addition of a diuretic.

BACKGROUND: An elevated heart rate is an established marker of cardiovascular risk. Previous analyses have suggested that ivabradine, a heart-rate-reducing agent, may improve outcomes in patients with stable coronary artery disease, left ventricular dysfunction, and a heart rate of 70 beats per minute or more.METHODS: We conducted a randomized, double-blind, placebo-controlled trial of ivabradine, added to standard background therapy, in 19,102 patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more (including 12,049 patients with activity-limiting angina [class ≥II on the Canadian Cardiovascular Society scale, which ranges from I to IV, with higher classes indicating greater limitations on physical activity owing to angina]). We randomly assigned patients to placebo or ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction.RESULTS: At 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minute in the ivabradine group versus 70.6±10.1 beats per minute in the placebo group. After a median follow-up of 27.8 months, there was no significant difference between the ivabradine group and the placebo group in the incidence of the primary end point (6.8% and 6.4%, respectively; hazard ratio, 1.08; 95% confidence interval, 0.96 to 1.20; P=0.20), nor were there significant differences in the incidences of death from cardiovascular causes and nonfatal myocardial infarction. Ivabradine was associated with an increase in the incidence of the primary end point among patients with activity-limiting angina but not among those without activity-limiting angina (P=0.02 for interaction). The incidence of bradycardia was higher with ivabradine than with placebo (18.0% vs. 2.3%, PCONCLUSIONS: Among patients who had stable coronary artery disease without clinical heart failure, the addition of ivabradine to standard background therapy to reduce the heart rate did not improve outcomes. (Funded by Servier; SIGNIFY Current Controlled Trials number, ISRCTN61576291.).

Critical limb ischaemia (CLI) is a particularly severe manifestation of lower limb atherosclerosis posing a major threat to both limb and life of affected patients. Besides arterial revascularisation, risk-factor modification and administration of antiplatelet therapy is a major goal in the treatment of CLI patients.Key elements of cardiovascular risk management are smoking cessation and treatment of hyperlipidaemia with dietary modification or statins. Moreover, arterial hypertension and diabetes mellitus should be adequately treated.In CLI patients not suitable for arterial revascularisation or subsequent to unsuccessful revascularisation, parenteral prostanoids may be considered. CLI patients undergoing surgical revascularisation should be treated with beta blockers. At present, neither gene nor stem-cell therapy can be recommended outside clinical trials. Of note, walking exercise is contraindicated in CLI patients due to the risk of worsening pre-existing or causing new ischaemic wounds.CLI patients are oftentimes medically frail and exhibit significant comorbidities. Co-existing coronary heart and carotid as well as renal artery disease should be managed according to current guidelines.Considering the above-mentioned treatment goals, interdisciplinary treatment approaches for CLI patients are warranted.Aim of the present manuscript is to discuss currently existing evidence for both the management of cardiovascular risk factors and treatment of co-existing disease and to deduct specific treatment recommendations.

OBJECTIVES: Despite a broad and efficient pharmacological antihypertensive armamentarium, blood pressure (BP) control is suboptimal and heterogeneous throughout Europe. Recent representative data from Switzerland are limited. The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerland in accordance with current guidelines. The influence of risk factors, target organ damage and medication on BP levels and control was also evaluated.METHODS : A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerland. 281 randomly selected physicians provided data on 5 consecutive hypertensive patients attending their practices for BP follow-up. Data were anonymously collected on demographics, comorbidities and current medication, and BP was recorded. Subsequent modification of pharmacological antihypertensive therapy was assessed.RESULTS : Data from 1376 patients were available. Mean age was 65 +/- 12 years, 53.9% were male subjects. 26.4% had complicated hypertension. Overall, BP control (

The arrhythmogenic effects of endothelin-1 (ET-1) are mediated via ETA-receptors, but the role of ETB-receptors is unclear. We examined the pathophysiologic role of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial infarction (MI). MI was induced by coronary ligation in two animal groups, namely in wild-type (n = 63) and in ETB-receptor-deficient (n = 61) rats. Using a telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour) and phase II (2-24 h) post-MI, with and without prior beta-blockade. Action potential duration at 90% repolarization (APD90) was measured from monophasic epicardial recordings and indices of sympathetic activation were assessed using fast-Fourier analysis of heart rate variability. Serum epinephrine and norepinephrine were measured with radioimmunoassay. MI size was similar in the two groups. There was a marked temporal variation in VT/VF duration; during phase I, it was higher (p = 0.0087) in ETB-deficient (1,519 +/- 421 s) than in wild-type (190 +/- 34 s) rats, but tended (p = 0.086) to be lower in ETB-deficient (4.2 +/- 2.0 s) than in wild-type (27.7 +/- 8.0 s) rats during phase II. Overall, the severity of VT/VF was greater in ETB-deficient rats, evidenced by higher (p = 0.0058) mortality (72.0% vs. 32.1%). There was a temporal variation in heart rate and in the ratio of low- to high-frequency spectra, being higher (

AIMS: To compare the treatment and outcomes of myocardial infarction patients in hospitals with and without catheterization laboratory. METHODS AND RESULTS: The Hellenic Infarction Observation Study was a countrywide registry of acute myocardial infarction, conducted during 2005-2006. The registry enrolled 1840 patients with myocardial infarction from 31 hospitals with a proportional representation of all types of hospitals and of all geographical areas. Out of these patients, 645 (35%) were admitted in 11 hospitals with and 1195 (65%) in 20 hospitals without catheterization laboratory. Patients admitted in hospitals with catheterization laboratory in comparison with patients admitted in hospitals without were younger (66+/-14 vs. 68+/-13, P1 22 vs. 23%). Reperfusion rates for ST-segment elevation myocardial infarction were 67% (43% lytic, 24% primary percutaneous coronary interventions) versus 56% (55% lytic, 1% percutaneous coronary interventions; P

SummaryAcute myocardial infarction is the leading cause of morbidity and mortality in the adult population of developed and developing nations. Although the prompt restoration of antegrade blood flow in the infarct-related coronary artery is the mean therapy for improving survival, reperfusion itself may cause damage to ischaemic myocardial tissue. This event is well known as “reperfusion injury”. Crucial mediators for cardiac damage in the reperfusion phases are oxidative stress, inflammation and leukocyte infiltration. Already approved and novel therapies might directly reduce these inflammatory processes. Treatments modulating chemokine secretion and activity should be considered as very promising approaches to reduce myocardial reperfusion injury.

OBJECTIVES: Hypertensive left ventricular hypertrophy (LVH) is associated with cardiomyocyte hypertrophy and an excess in myocardial collagen. Myocardial fibrosis may cause diastolic dysfunction and heart failure. Circulating levels of the carboxy-terminal propeptide of procollagen type I (PICP), an index of collagen type I synthesis, correlate with the extent of myocardial fibrosis. This study examines myocardial fibrosis in relation to blood pressure, left ventricular mass (LVM), and diastolic function. METHODS: We examined PICP levels in 115 patients with hypertensive LVH, 38 with hypertension but no hypertrophy, and 38 normotensive subjects. Patients with LVH were subsequently randomly assigned to the angiotensin II type 1 receptor blocker irbesartan or the beta1 receptor blocker atenolol for 48 weeks. Diastolic function was evaluated by tissue velocity echocardiography (n=134). We measured basal septal wall velocities of early (Em) and late (Am) diastolic myocardial wall motion, Em velocity deceleration time (E-decm), and isovolumic relaxation time (IVRTm). RESULTS: Compared with the normotensive group, PICP was elevated and left ventricular diastolic function was impaired in the hypertensive groups, with little difference between patients with and without LVH. PICP related to blood pressure, IVRTm, Em, and E/Em, but not to LVM. Irbesartan and atenolol reduced PICP similarly. Only in the irbesartan group did changes in PICP relate to changes in IVRTm, and LVM. CONCLUSION: Myocardial fibrosis and diastolic dysfunction are present in hypertension before LVH develops. The findings with irbesartan suggest a role for angiotensin II in the control of myocardial fibrosis and diastolic function in patients with hypertension with LVH.

BACKGROUND: The objective of our study was to assess hospital-to-hospital variations for the management and treatment of heart failure (HF) patients. METHODS: We performed a cross-sectional study among randomly selected patients with ICD-10 (International Classification of Disease, 10th revision) HF hospitalised in three Swiss university hospitals in 1999. Demographic characteristics, risk factors, symptoms and findings at admission and discharge medications were abstracted. The main outcome measure was the percentage of patients receiving appropriate management and treatment as defined by quality of care indicators derived from evidence-based guidelines. Quality indicators were considered only when they could be applied (no contra-indications). RESULTS: Among 1153 eligible patients with HF the mean age (SD) was 75.3 (12.7), 54.3% were male. Among potential candidates for specific interventions left ventricular function (LVF) was determined in 68.5% of patients; 53.8% received target dose of angiotensin converting enzyme inhibitors (ACEI), 86.0% any dose of angiotensin receptor blockers; 21.9% b-blockers, and 62.1% anticoagulants at discharge. Compared to hospital B (reference), the adjusted odds ratios (OR) (95% CI) for LVF not determined were 3.82 (2.50 to 5.85) in hospital A and 3.25 (1.78 to 5.93) in hospital C. The adjusted OR (95% CI) for not receiving target dose ACEI was 1.76 (0.95 to 3.26) for hospital A and 3.20 (1.34 to 7.65) for hospital C compared to hospital B. CONCLUSIONS: Apparently, important hospital-to-hospital variations in the quality of care given to patients with HF could have existed between three academic medical centers.

Aim: To determine the ocular haemodynamic response to gas perturbations in glaucoma. Methods: Intraocular pressure (IOP), systemic systolic and diastolic blood pressure (SBP and DBP), and retrobulbar blood flow velocities, measured by colour Doppler imaging (CDI), were recorded at two visits. CDI was used to measure peak systolic and end diastolic velocities (PSV and EDV) and resistance index (RI) in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs). At the first visit, measurements were taken at baseline (B1: breathing room air) and during isoxic hypercapnia (end tidal PCO2 increased 15% above baseline) in 16 normal subjects and 12 patients with glaucoma. On another day, measurements were repeated at a second baseline (B2) and during hyperoxia (100% oxygen breathing) for 15 normal subjects and 13 glaucoma patients. Baseline systemic data were compared using paired t tests; REANOVA was performed to compare group differences at baseline and to determine the vessel response to each condition. Fisher’s LSD was used for post hoc comparison. Results: Baseline OA PSV was lower for the glaucoma than for the normal group (p = 0.047); the groups were otherwise similar at baseline. IOP demonstrated no response to hypercapnia, but reduced during hyperoxia for both the normal subjects (p

Current clinical guidelines state that only beta-blockers, diuretics, calcium channel antagonists and ACE inhibitors should be used for initial pharmacotherapy for uncomplicated hypertension. On basis of experience, efficacy and costs beta-blockers and diuretics are first choice. However, the importance of the renin-angiotensin-aldosterone-system in the pathophysiology of hypertensive end-organ damage is increasingly recognised nowadays, and modulation of this system may therefore exert favourable effects on cardiovascular and cerebrovascular complications. In the LIFE study, a recently published double-blinded, randomised trial, the angiotensin-II receptor (A-II) antagonist losartan was compared with the beta-blocker atenolol in patients with essential hypertension and left ventricular hypertrophy (LVH). Patients randomised to the A-II antagonist suffered statistically significantly fewer clinical end-points, specifically fewer cerebrovascular accidents, whereas both treatments resulted in a similar decrease in blood pressure. In the subset of diabetic patients, the use of the A-II antagonist yielded an even more favourable outcome. In our opinion, it should now also be permitted to prescribe A-II antagonists as initial pharmacotherapy for patients with uncomplicated essential hypertension. It might be considered to prescribe A-II antagonists as preferred treatment for patients with essential hypertension and known LVH, especially in diabetic patients.

Secondary prevention of coronary artery disease markedly reduces cardiovascular mortality and non-fatal endpoints. Outpatient care of subjects with coronary artery disease has been assessed in several European countries, but no current data is available for Switzerland. A random sample of office-based physicians across Switzerland recorded current drug prescription of outpatients with coronary artery disease in the years 2000/2001 by means of a mail questionnaire. We assessed treatment frequencies according to different patient characteristics. 565 patients were included (mean age 68 +/- 11 years, 75% male). There was no evidence for differences in drug utilisation among the regions. Drug prescription rates for antithrombotic agents, beta-blockers, ACE-inhibitors/angiotensin receptor blockers and lipid lowering drugs were 91%, 58%, 50% and 63% respectively. Lower treatment rates were observed among patients >70 years and in those without a history of myocardial infarction or coronary revascularisation. Forty-nine percent of the patients had a blood pressure >140/>90, and 60% had lipid readings above the intervention cut-off according to the Swiss recommendations. Among those without a history of myocardial infarction or coronary revascularisation, the respective figures were 60% and 80%. Compared to former surveys evidence based drug prescription has improved in Switzerland. Despite this, therapeutic goals for cholesterol levels and blood pressure are not being reached in a large proportion of patients. A high risk group for under use of evidence based drugs are patients without a history of myocardial infarction or coronary revascularisation.

We analyzed a local database including 468 consecutive patients who underwent elective aortic abdominal surgery over an 8-yr period in a single institution. A new cardioprotective perioperative protocol was introduced in January 1997, and we questioned whether perioperative cardiac outcome could be favorably influenced by the application of a stepwise cardiovascular evaluation based on the American College of Cardiology/American Heart Association guidelines and by the use of antiadrenergic drugs. Clonidine was administered during surgery, and beta-blockers were titrated after surgery to achieve heart rates less than 80 bpm. We compared data of two consecutive 4-yr periods (1993-1996 [control period] versus 1997-2000 [intervention period]). Implementation of American College of Cardiology/American Heart Association guidelines was associated with increased preoperative myocardial scanning (44.3% vs 20.6%; P0.05) and coronary revascularization (7.7% vs 0.8%; P0.05). During the intervention period, there was a significant decrease in the incidence of cardiac complications (from 11.3% to 4.5%) and an increase in event-free survival at 1 yr after surgery (from 91.3% to 98.2%). Multivariate regression analysis showed that the combined administration of clonidine and beta-blockers was associated with a decreased risk of cardiovascular events (odds ratio, 0.3; 95% confidence interval, 0.1-0.8), whereas major bleeding, renal insufficiency, and chronic obstructive pulmonary disease were predictive of cardiac complications. In conclusion, cardiac testing was helpful to identify a small subset of high-risk patients who might benefit from coronary revascularization. Sequential and selective antiadrenergic treatments were associated with improved postoperative cardiac outcome.Implementation of American College of Cardiology/American Heart Association guidelines and use of antiadrenergic drugs were associated with better cardiac outcomes after major vascular surgery.

Whereas intraocular pressure is considered a major risk factor in glaucoma, growing evidence now indicates that ocular ischemia plays a major role too. By virtue of this and because many existing medications are able to interact with vasculature, altering ocular blood flow, it is essential that current and future medications for glaucoma be evaluated for their effect on ocular circulation. The authors review published papers examining the effect of topical and some systemic medications on ocular blood flow, focusing mostly on data from the human eye. The authors provide a comprehensive review on the effect of subclasses of medications (eg, carbonic anhydrase inhibitors, beta-blockers, alpha-adrenergic agonists, and prostaglandin analogues on optic nerve head, and on retinal, choroidal, and retrobulbar circulation. The various claims for enhancements or reduction of ocular circulation within each class of medication are reviewed and evaluated.