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Heartbeat: Renin-angiotensin system blockade for prevention of cardiovascular disease

2017-08-15T02:57:26-07:00

Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) medications both target the renin–angiotensin system (RAS) and both are recommended in treatment of several types of cardiovascular disease (CVD). However, the optimal choice between these 2 groups of medications for prevention of CVD is not well established. Potier and colleagues1 compared the relative effectiveness of ACEIs versus ARBs for prevention of adverse outcomes in over 40 thousand patients at high cardiovascular risk enrolled in the observational Reduction of Atherothrombosis for Continued Health (REACH) registry. This international registry includes adults over age 45 years with known CVD or with at least 3 risk factors for atherosclerosis; the current analysis includes only those subjects taking an ACEI or ARB at baseline who had 4-year follow-up data. Medical therapy was provided by individual physician practices for standard indications. Baseline conditions included a history of hypertension (91%), heart failure (16%), atrial fibrillation/flutter...




Ensuring adherence to therapy with anticoagulation in patients with atrial fibrillation

2017-08-15T02:57:27-07:00

Atrial fibrillation (AF) is a significant burden for healthcare systems due to increased morbidity and mortality rates. It is a major cause of ischaemic stroke, which is considered one of the most serious and disabling complications of AF. Stroke prevention with oral anticoagulation (OAC) by vitamin K antagonists (VKA) or non-vitamin K antagonists (NOAC) is therefore a significant component of AF management. Both VKAs and NOACs are effective for the prevention of stroke in AF; however, stringent adherence to the recommended treatment regimen is crucial, both from a prescriber’s and a patient’s perspective. Worldwide, stroke prevention in AF is suboptimal, with poor adherence to international guideline recommendations.1 Poor adherence is a major barrier to effective stroke prevention, reflected in inadequate time in therapeutic range (TTR) with VKA treatment. A proposed advantage of NOAC therapy is the lack of requirement for routine blood monitoring for therapeutic levels. However,...




Angiotensin-converting enzyme inhibitors versus receptor blockers: is one better than the other for cardiovascular prevention?

2017-08-15T02:57:27-07:00

Inhibition of the renin–angiotensin system (RAS) is currently considered as an established strategy for cardiovascular prevention, and indeed, RAS inhibitors are widely used in patients with cardiovascular disease or those at high risk of cardiovascular events. ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are two major classes of RAS inhibitors. There remain two important controversies regarding the effects of RAS inhibitors; one question is whether RAS inhibitors have anti-atherosclerotic effects beyond lowering blood pressure. Accumulated evidence demonstrates that the benefit of RAS inhibition is most prominent in patients with heart failure or those who have suffered from myocardial infarction (MI), suggesting that RAS inhibitors prevent cardiovascular events and improve outcomes in patients with cardiac injury and/or dysfunction. However, less evidence is available about cardiovascular risk reduction by RAS inhibitors independent of their blood pressure lowering effects in patients with arteriosclerotic diseases or those at a high risk but...




Declining incidence and prevalence of Eisenmenger syndrome in the developed world: a triumph of modern medicine

2017-08-15T02:57:27-07:00

In 1897, Dr Victor Eisenmenger described a 32-year-old man with a history of cyanosis and progressive exertional breathlessness since childhood. The patient developed heart failure in his 30s and, thereafter, died suddenly following massive haemoptysis. His postmortem showed a large ventricular septal defect (VSD). However, the haemodynamic and pathophysiological significance of large intracardiac defects remained unclear until the advent of cardiac catheterisation. It was not until the late 1950s, when Paul Wood in his seminal work elegantly described the flow and pressure overload to the pulmonary circulation caused by large cardiac defects, resulting in a gradual increase in pulmonary vascular resistance and, over time, shunt reversal leading to cyanosis. Paul Wood also recognised that Eisenmenger syndrome (ES) may develop in patients with an isolated, large VSD and also in those with a large patent ductus arteriosus, atrioventricular septal defect or even an isolated atrial septal defect.1

In ES,...




Efficacy and safety of the subcutaneous implantable cardioverter defibrillator: a systematic review

2017-08-15T02:57:27-07:00

Background

Subcutaneous implantable cardioverter defibrillators (S-ICDs) are considered an alternative to conventional transvenous ICDs (TV-ICDs) in patients not requiring pacing.

Methods

We searched MEDLINE and EMBASE for studies evaluating efficacy and safety outcomes in S-ICD patients. Outcomes were pooled across studies.

Results

Sixteen studies were included with 5380 participants (mean age range 33–56 years). Short-term follow-up data were available for 1670 subjects. The most common complication was pocket infection, affecting 2.7%. Other complications included delayed wound healing (0.6%) and wound discomfort (0.8%). 3.8% of S-ICDs were explanted, most commonly for pocket infection. Mortality rates in hospital (0.4%) and during follow-up (3.4% from 12 studies reporting) were low. Incidence of ventricular arrhythmia varied from 0% to 12%. Overall shock efficacy exceeded 96%. Inappropriate shocks affected 4.3% and was most commonly caused by T-wave oversensing.

Conclusions

Although long-term randomised data are lacking, observational data suggest similar shock efficacy and short-term complication rates between the S-ICD and TV-ICD.




Contemporary natural history of bicuspid aortic valve disease: a systematic review

2017-08-15T02:57:27-07:00

We performed a systematic review of the current state of the literature regarding the natural history and outcomes of bicuspid aortic valve (BAV). PubMed and the reference lists of the included articles were searched for relevant studies reporting on longitudinal follow-up of BAV cohorts (mean follow-up ≥2 years). Studies limited to patients undergoing surgical interventions were excluded. 13 studies (11 502 patients with 2–16 years of follow-up) met the inclusion criteria. There was a bimodal age distribution (30–40 vs ≥50 years), with a 3:1 male to female ratio. Complications included moderate to severe aortic regurgitation (prevalence 13%–30%), moderate to severe aortic stenosis (12%–37%), infective endocarditis (2%–5%) and aortic dilatation (20%–40%). Aortic dissection or rupture was rare, occurring in 38 patients (0.4%, 27/6446 in native BAV and 11/2232 in post). With current aggressive surveillance and prophylactic surgical interventions, survival in three out of four studies was similar to that of a matched general population. In this systematic review, valvular dysfunction warranting surgical intervention in patients with BAV were common, aortic dissection was rare and, with the current management approach, survival was similar to that of the general population.




Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation

2017-08-15T02:57:27-07:00

Objective

Dabigatran and rivaroxaban are novel oral anticoagulants (NOACs) approved for stroke prevention in atrial fibrillation (AF). Although NOACs are more convenient than warfarin, their lack of monitoring may predispose patients to non-persistence. Limited information is available on NOAC non-persistence rates and related clinical outcomes in clinical practice.

Methods

We conducted a retrospective cohort study using administrative data from Ontario, Canada, from January 1998 to March 2014 of patients with AF who were dispensed dabigatran or rivaroxaban. Non-persistence was defined as a gap in dabigatran or rivaroxaban prescriptions ≥14 days. A multivariable Cox proportional hazards model was used to estimate the primary composite outcome of stroke, transient ischaemic attack (TIA) and mortality associated with non-persistence.

Results

The cohort consisted of 15 857 dabigatran (age 80.7±6.7 year) and 10 119 rivaroxaban users (age 77.0±7.1 year) with women comprising 52% of each medication group. At 6 months, 36.4% of patients were non-persistent to dabigatran, while 31.9% of patients were non-persistent to rivaroxaban. Stroke/TIA/death was significantly higher for those non-persistent to dabigatran (HR 1.76 (95% CI 1.60 to 1.94); p<0.0001) or rivaroxaban (HR 1.89 (95% CI 1.64 to 2.19); p<0.0001) compared with those who were persistent. Risk of stroke/TIA was markedly higher in non-persistent patients to dabigatran (HR 3.75 (95% CI 2.59 to 5.43); p<0.0001) and rivaroxaban (HR 6.25 (95% CI 3.37 to 11.58); p<0.0001) than those persistent.

Conclusions

NOAC non-persistence rates are high in clinical practice, with approximately one in three patients becoming non-persistent to dabigatran or rivaroxaban within 6 months after drug initiation. Non-persistence with either dabigatran or rivaroxaban is significantly associated with worse clinical outcomes of stroke/TIA/death.




Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high vascular risk

2017-08-15T02:57:27-07:00

Objective

ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely prescribed in patients with high cardiovascular (CV) risk. However, whether both classes have equivalent effectiveness to prevent CV events remains unclear. The aim of this study was to compare the incidence of major CV events between ACEI and ARB users.

Methods

The Reduction of Atherothrombosis for Continued Health registry is an observational study who enrolled 69 055 individuals with high CV risk. Among them, 40 625 patients (ACEIs 67.9% and ARBs 32.1%) were included. Main outcome was rates of CV mortality, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for CV disease at 4 years.

Results

In a propensity score-adjusted cohort, the incidence of the primary outcome was lower in patients on ARBs compared with ACEIs (29.2% vs 33.4%; adjusted HR 0.90; 95% CI 0.86 to 0.95; p<0.001). Similar results were observed for CV (6.9% vs 8.2%; HR 0.83; 95% CI 0.75 to 0.93; p=0.001) and all-cause mortality (11.6% vs 12.6%; HR 0.89; 95% CI 0.82 to 0.97; p=0.005). Analyses using propensity score matching yielded similar results. History of diabetes or estimated glomerular filtration rate did not affect the results. ARB use was associated with lower rates of all-cause mortality in secondary prevention but not in primary prevention patients (p-value for interaction=0.03).

Conclusion

ARB use appears to be associated with 10% lower rates of CV events compared with ACEIs, especially in patients with established CV disease. Our results suggest that ARBs may provide superior protection against CV events than ACEIs in high-risk patients in real-world practice.




Association of 6-year waist circumference gain and incident hypertension

2017-08-15T02:57:27-07:00

Objective

The risk of incident hypertension with gain in waist circumference (WC) has not been fully addressed among Chinese adults.

Methods

A total of 10 265 non-hypertensive participants ≥18 years old who underwent health examinations in rural China were recruited in 2007–2008 and followed up in 2013–2014. Participants were classified by gender according to categories of per cent WC gain at follow-up: ≤–2.5%, –2.5% to 2.5%, 2.5% to 5% and >5%. Relative risk (RR) and 95% CI values for effect of WC gain on the incident hypertension were calculated by using modified Poisson regression models.

Results

During 6 years of follow-up, we identified 2027 hypertension cases (1213 women). From baseline to follow-up, the prevalence of abdominal obesity increased from 21.1% to 29.6% for men and 49.8% to 61.9% for women. As compared with participants who were not abdominally obese at both baseline and follow-up, both genders who were abdominally obese at follow-up showed greater risk of hypertension regardless of abdominal obesity status at baseline. Compared with the reference group of –2.5% to 2.5% change in WC, with >5% WC gain, risk of incident hypertension was increased for men (RR=1.34, 95% CI 1.15 to 1.57) and women (RR=1.28, 95% CI 1.10 to 1.50). The hypertension risk decreased for men with WC loss ≥2.5% (RR=0.81, 95% CI 0.67 to 0.98).

Conclusions

Abdominal obesity is seriously prevalent in China. The risk of hypertension increased significantly with increasing WC for both genders in a rural Chinese population.




Epidemiological changes in Eisenmenger syndrome in the Nordic region in 1977-2012

2017-08-15T02:57:27-07:00

Objective

Improved diagnostic tools, timely closure of the shunt and a better understanding of the complexity of Eisenmenger syndrome (ES) have led to improved care and treatment in tertiary centres. These may have decreased the incidence of ES and improved survival of patients with ES, although evidence is still lacking. The aim of this study was to investigate temporal changes in incidence, prevalence and mortality in patients with ES for 35 years in the Nordic region.

Methods

This was a retrospective population-based study including 714 patients with ES. Survival analysis was performed based on all-cause mortality and accounting for immortal time bias.

Results

The incidence of ES decreased from 2.5/million inhabitants/year in 1977 to 0.2/million inhabitants/year in 2012. Correspondingly, prevalence decreased from 24.6 to 11.9/million inhabitants. The median survival was 38.4 years, with 20-year, 40-year and 60-year survival of 72.5%, 48.4%, and 21.3%, respectively. Complex lesions and Down syndrome were independently associated with worse survival (HR 2.2, p<0.001 and HR 1.8, p<0.001, respectively). Age at death increased from 27.7 years in the period from 1977 to 1992, to 46.3 years from July 2006 to 2012 (p<0.001).

Conclusions

The incidence and prevalence of ES in the Nordic region have decreased markedly during the last decades. Furthermore, the median age at death increased throughout the study period, indicating prolonged life expectancy in the ES population. However, increasing age represents decreased incidence, rather than improved survival. Nonetheless, longevity with ES is still shorter than in the background population.




Regional left ventricular function does not predict survival in ischaemic cardiomyopathy after cardiac surgery

2017-08-15T02:57:27-07:00

Objectives

To define the prognostic contribution of global and regional left ventricular (LV) function measurements in patients with ischaemic cardiomyopathy randomised to coronary artery bypass graft surgery (CABG) with (n=501) or without (n=499) surgical ventricular reconstruction (SVR).

Methods

Novel multivariable methods to analyse global and regional LV systolic function were used to better formulate prediction models for long-term mortality following CABG with or without SVR in the entire cohort of 1000 randomised SVR hypothesis patients. Key clinical variables were included in the analysis. Regional function was classified according to the discreteness of anteroapical hypokinesia and akinesia into those most likely to benefit from SVR, those least likely and those felt to have intermediate likelihood of benefit from SVR.

Results

The most prognostic clinical variables identified in multivariable models include creatinine, LV end-systolic volume index (ESVI), age and NYHA (New York Heart Association) class. Addition of LV ejection fraction, LV end-diastolic volume index and regional function assessment did not contribute additional power to the model. Subgroup analysis based on regional function did not identify a cohort in which SVR improved mortality.

Conclusions

ESVI is the single parameter of LV function most predictive of mortality in patients with LV systolic dysfunction following CABG with or without SVR in multivariable models that include all key clinical and LV systolic function parameters. Assessment of regional cardiac function does not enhance prediction of mortality nor identify a subgroup for which SVR improves mortality. These results do not support elective addition of LV reconstruction surgery in patients undergoing CABG.

Trial registration number

NCT00023595.




Cancer antigen-125 plasma level as a biomarker of new-onset atrial fibrillation in postmenopausal women

2017-08-15T02:57:27-07:00

Objective

Plasma cancer antigen (CA)-125 is a tumour marker recently shown to be associated with systolic heart failure and new-onset atrial fibrillation (AF) after myocardial infarction. However, no reports have described the relationship between CA-125 and new-onset AF in healthy postmenopausal women. The aim of the present study was to evaluate the relationship between CA-125 and new-onset AF in postmenopausal women.

Methods

Between 2005 and 2015, 2086 women, including 1012 postmenopausal women, visited our hospital for annual health check-ups. We excluded patients with systolic dysfunction, chronic inflammatory disease, chronic obstructive pulmonary disease, histories of AF or neoplastic diseases. A total of 746 postmenopausal women underwent thorough physical examinations, including those for biomarkers such as brain natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP) and CA-125.

Results

During the 10-year observation period, AF was documented in 31 participants (4.2%). The mean age of participants developing AF (75±6 years) was higher than that of those without AF (68±8 years). Participants developing AF showed significantly higher CA-125 (11.4±6.3 U/mL) and hs-CRP (0.10±0.11 mg/dL) levels than did those without AF (7.7±3.2 U/mL, p<0.01; 0.07±0.08 mg/dL, p<0.05). Cox regression analyses revealed ageing (HR 1.3; 95% CI 1.08 to 1.57; p<0.01) and plasma CA-125 levels (HR 1.29; 95% CI 1.10 to 1.51; p=0.02) as independent predictors of AF.

Conclusions

High CA-125 levels might be associated with new-onset AF in healthy postmenopausal women.




Arrhythmia risk and {beta}-blocker therapy in pregnant women with long QT syndrome

2017-08-15T02:57:27-07:00

Background

Pregnancy is one of the biggest concerns for women with long QT syndrome (LQTS).

Objectives

This study investigated pregnancy-related arrhythmic risk and the efficacy and safety of β-blocker therapy for lethal ventricular arrhythmias in pregnant women with LQTS (LQT-P) and their babies.

Methods

136 pregnancies in 76 LQT-P (29±5 years old; 22 LQT1, 36 LQT2, one LQT3, and 17 genotype-unknown) were enrolled. We retrospectively analysed their clinical and electrophysiological characteristics and pregnancy outcomes in the presence (BB group: n=42) or absence of β-blocker therapy (non-BB group: n=94).

Results

All of the BB group had been diagnosed with LQTS with previous events, whereas 65% of the non-BB group had not been diagnosed at pregnancy. Pregnancy increased heart rate in the non-BB group; however, no significant difference was observed in QT and Tpeak–Tend intervals between the two groups. In the BB group, only two events occurred at postpartum, whereas 12 events occurred in the non-BB group during pregnancy (n=6) or postpartum period (n=6). The frequency of spontaneous abortion did not differ between the two groups. Fetal growth rate and proportion of infants with congenital malformation were similar between the two groups, but premature delivery and low birthweight infants were more common in those taking BB (OR 4.79, 95% CI 1.51 to 15.21 and OR 3.25, 95% CI 1.17 to 9.09, respectively).

Conclusions

Early diagnosis and β-blocker therapy for high-risk patients with LQTS are important for prevention of cardiac events during pregnancy and the postpartum period, and β-blocker therapy may be tolerated for babies in LQT-P cases.




Acute arrhythmias in adults with congenital heart disease

2017-08-15T02:57:27-07:00

Learning objectives

  • Recognise important ECG characteristics of common arrhythmias in adults with congenital heart disease (CHD).

  • Identify salient differences in clinical presentation of acute arrhythmia in this group.

  • Develop a management approach to the patient with CHD with acute arrhythmia.

  • Introduction

    Before the advent of central shunts and cardiopulmonary bypass, the natural history studies characterising mortality in those with complex congenital heart disease (CHD) described dismal long-term outcome statistics with few reaching adulthood.1 Subsequent to these innovations—and coupled with outstanding advances in surgical techniques and cardiological care—the practising community has witnessed the emergence of a new population of survivors. Mortality has dropped profoundly; yet with the improved longevity, most of the patients with CHD with moderate/severely complex lesions (table 1) remain at high risk for recurrent haemodynamic issues.2 Yet, the most frequent cause for hospitalisation is arrhythmia,...




    Cardiovascular highlights from non-cardiology journals

    2017-08-15T02:57:27-07:00

    Bleeding versus thromboembolic protection in atrial fibrillation and coronary stent procedures

    Five to 8% of people undergoing percutaneous coronary intervention (PCI) also have atrial fibrillation (AF). The optimal antiplatelet / anticoagulant regimen in these individuals remains unclear as stroke and stent thrombosis prevention need to be balanced against the risks of major bleeding. The PIONEER AF-PCI trial randomised 2124 patients with AF who had undergone PCI to 1 of 3 arms: 15 mg rivaroxaban + a P2Y12 inhibitor alone for 12 months, 2.5 mg of twice daily rivaroxaban + a P2Y12 inhibitor and aspirin (DAPT) for 1, 6 or 12 months or warfarin + DAPT for 1, 6 or 12 months. The predominant P2Y12 inhibitor was clopidogrel (approx. 90%). The primary endpoint was clinically significant bleeding while efficacy - both myocardial infarction and stroke were secondary end-points. Both rivaroxaban arms demonstrated significant reductions in major bleeding relative to the warfarin...




    Dyspnoea on exertion in a 53-year-old woman

    2017-08-15T02:57:27-07:00

    Clinical introduction

    A 53-year-old woman with no previous medical history complained of easy fatigue over the last 6 months. She had a positive family history for coronary artery disease but no other risk factors. On physical examination, a 3/6 pansystolic murmur was heard over the apex, and the lung auscultation was unremarkable. Her ECG showed a left anterior fascicular block, with poor R wave progression in the anterior leads (see online ). A subsequent echocardiogram revealed a slightly dilated for the patient’s body surface area (BSA) (1.73 m2) left ventricle (55/35 mm), with preserved systolic function and a moderate functional mitral regurgitation. The estimated pulmonary artery pressure was 45 mm Hg. During treadmill radionuclide scintigraphy, her exercise tolerance was normal, with good inotropic response, and 96% oxygen saturation at rest and at peak exercise. A 2 mm ST segment depression was noted at peak effort, which persisted well into recovery (see online ). The scintigraphy scan showed extensive reversible anteroapical wall ischaemia (see online ). At this point she was referred to us for right and left heart catheterisation. Intracardiac pressures and saturations were: right atrium (RA)RA=3 mm Hg, right ventricle (RV)=26/3 mm Hg, Pulmonary artery (PA)=26/10/mean 16 mm Hg, pulmonary capillary wedge pressure (PCWP)=11 mm Hg, left ventricle (LV)=110/10 mm Hg, Aorta (Ao)=110/60/mean 80 mm Hg, Superior vena cava saturation (SVCsat)=62%, RAsat=62%, PAsat=78%, Aosat=96% and estimated pulmonary to systematic flow ratio (Qp/Qs)=1.8. Her coronary angiography and CT angiography are shown in figure 1A,B.

    Figure 1

    Coronary and CT angiograms.

    Question

    What is the most likely diagnosis?

  • Right coronary fistula to right ventricle

  • Kawasaki disease with fistula

  • Anomalous origin of the left coronary artery from the pulmonary artery

  • Persistent truncus arteriosus