The mechanisms mediating kidney injury and repair in humans with atherosclerotic renal artery stenosis (ARAS) remain poorly understood. We hypothesized that the stenotic kidney releases inflammatory mediators and recruits progenitor cells to promote regeneration.
Methods and results
Essential hypertensive (EH) and ARAS patients (n= 24 each) were studied during controlled sodium intake and antihypertensive treatment. Inferior vena cava (IVC) and renal vein (RV) levels of CD34+/KDR+ progenitor cells, cell adhesion molecules, inflammatory biomarkers, progenitor cell homing signals, and pro-angiogenic factors were measured in EH and ARAS, and their gradient and net release compared with systemic levels in matched normotensive controls (n= 24). Blood pressure in ARAS was similar to EH, but the glomerular filtration rate was lower. Renal vein levels of soluble E-Selectin, vascular cell adhesion molecule-1, and several inflammatory markers were higher in the stenotic kidney RV vs. normal and EH RV (P< 0.05), and their net release increased. Similarly, stem-cell homing factor levels increased in the stenotic kidney RV. Systemic CD34+/KDR+ progenitor cell levels were lower in both EH and ARAS and correlated with cytokine levels. Moreover, CD34+/KDR+ progenitor cells developed a negative gradient across the ARAS kidney, suggesting progenitor cell retention. The non-stenotic kidney also showed signs of inflammatory processes, which were more subtle than in the stenotic kidney.
Renal vein blood from post-stenotic human kidneys has multiple markers reflecting active inflammation that portends kidney injury and reduced function. CD34+/KDR+ progenitor cells sequestered within these kidneys may participate in reparative processes. These inflammation-related pathways and limited circulating progenitor cells may serve as novel therapeutic targets to repair the stenotic kidney.
Renovascular hypertension; Progenitor cells; Inflammatory biomarkers; Renal artery stenosis; Cytokines
Current knowledge on the prognosis of metabolically healthy but obese phenotype is limited due to the exclusive use of the body mass index to define obesity and the lack of information on cardiorespiratory fitness. We aimed to test the following hypotheses: (i) metabolically healthy but obese individuals have a higher fitness level than their metabolically abnormal and obese peers; (ii) after accounting for fitness, metabolically healthy but obese phenotype is a benign condition, in terms of cardiovascular disease and mortality.
Methods and results
Fitness was assessed by a maximal exercise test on a treadmill and body fat per cent (BF%) by hydrostatic weighing or skinfolds (obesity = BF% ≥25 or ≥30%, men or women, respectively) in 43 265 adults (24.3% women). Metabolically healthy was considered if meeting 0 or 1 of the criteria for metabolic syndrome. Metabolically healthy but obese participants (46% of the obese subsample) had a better fitness than metabolically abnormal obese participants (P < 0.001). When adjusting for fitness and other confounders, metabolically healthy but obese individuals had lower risk (30–50%, estimated by hazard ratios) of all-cause mortality, non-fatal and fatal cardiovascular disease, and cancer mortality than their metabolically unhealthy obese peers; while no significant differences were observed between metabolically healthy but obese and metabolically healthy normal-fat participants.
(i) Higher fitness should be considered a characteristic of metabolically healthy but obese phenotype. (ii) Once fitness is accounted for, the metabolically healthy but obese phenotype is a benign condition, with a better prognosis for mortality and morbidity than metabolically abnormal obese individuals.
Cardiovascular diseases; Heart diseases; Metabolic syndrome; Mortality; Obesity; Physical fitness
Real-time MRI creates images with superb tissue contrast that may enable radiation-free catheterization. Simple procedures are the first step towards novel interventional procedures. We aim to perform comprehensive transfemoral diagnostic right heart catheterization in an unselected cohort of patients entirely using MRI guidance.
Methods and results
We performed X-ray and MRI-guided transfemoral right heart catheterization in consecutive patients undergoing clinical cardiac catheterization. We sampled both cavae and both pulmonary arteries. We compared success rate, time to perform key steps, and catheter visibility among X-ray and MRI procedures using air-filled or gadolinium-filled balloon-tipped catheters. Sixteen subjects (four with shunt, nine with coronary artery disease, three with other) underwent paired X-ray and MRI catheterization. Complete guidewire-free catheterization was possible in 15 of 16 under both. MRI using gadolinium-filled balloons was at least as successful as X-ray in all procedure steps, more successful than MRI using air-filled balloons, and better than both in entering the left pulmonary artery. Total catheterization time and individual procedure steps required approximately the same amount of time irrespective of image guidance modality. Catheter conspicuity was best under X-ray and next-best using gadolinium-filled MRI balloons.
In this early experience, comprehensive transfemoral right heart catheterization appears feasible using only MRI for imaging guidance. Gadolinium-filled balloon catheters were more conspicuous than air-filled ones. Further workflow and device enhancement are necessary for clinical adoption.
Catheterization; Magnetic resonance imaging; Interventional cardiovascular MRI; Pulmonary artery
As obesity-related cardiovascular mortality, although elevated when compared with normal weight, is lower in females than in males at every body mass index (BMI) level, we aimed to investigate gender-specific differences in left ventricular (LV) hypertrophy in obesity, which themselves have been shown to have varying prognostic value.
Method and results
In total, 741 subjects (female, n = 399) without identifiable cardiovascular risk factors (BMI 15.7–59.2 kg/m2) underwent cardiovascular magnetic resonance (1.5 T) to determine LV mass, end-diastolic volume (EDV, mL), and LV mass/volume ratio (LVM/VR). Across both sexes, there was a strong positive correlation between BMI and LV mass (male r = 0.44, female r = 0.57, both P < 0.001), with males showing a greater LV hypertrophic response (male +2.3 vs. female +1.6 g per BMI point increase, P = 0.001). Concentric hypertrophy was present in both sexes and LVM/VR positively correlated to BMI (male r = 0.45, female r = 0.29, both P < 0.001) on linear regression analysis. However, the degree of concentric hypertrophy was greater in males (male +0.13 vs. female +0.06 LVM/VR increase per BMI point increase, P = 0.001). On the other hand, females showed a greater LV cavity dilatory response (female +1.1 vs. male +0.3 mL per BMI point increase, P < 0.001). Indeed, in contrast to females, where BMI and LV-EDV were positively correlated (r = 0.38, P < 0.001), BMI did not correlate with EDV in men (r = 0.03, P = 0.62).
In the absence of traditional cardiovascular risk factors, obese men show predominantly concentric hypertrophy, whereas obese women exhibit both eccentric and concentric hypertrophy. As concentric hypertrophy is more strongly related to cardiovascular mortality than eccentric hypertrophy, our observations may explain the observed gender difference in obesity-related mortality.
Gender; LV hypertrophy; Obesity; Cardiovascular magnetic resonance imaging
Left atrial (LA) structural and functional abnormalities may be subclinical phenotypes, which identify individuals at increased risk of adverse outcomes.
Methods and results
Maximum LA volume (LAmax) and LA emptying fraction (LAEF) were measured via cardiac magnetic resonance imaging in 1802 participants in the Dallas Heart Study. The associations of LAEF and LAmax indexed to body surface area (LAmax/BSA) with traditional risk factors, natriuretic peptide levels, and left ventricular (LV) structure [end-diastolic volume (EDV) and concentricity0.67 (mass/EDV0.67)] and function (ejection fraction) were assessed using linear regression analysis. The incremental prognostic value of LAmax/BSA and LAEF beyond traditional risk factors, LV ejection fraction, and LV mass was assessed using the Cox proportional-hazards model. Both increasing LAmax/BSA and decreasing LAEF were associated with hypertension and natriuretic peptide levels (P < 0.05 for all). In multivariable analysis, LAmax/BSA was most strongly associated with LV end-diastolic volume/BSA, while LAEF was strongly associated with LV ejection fraction and concentricity0.67. During a median follow-up period of 8.1 years, there were 81 total deaths. Decreasing LAEF [hazard ratio (HR) per 1 standard deviation (SD) (8.0%): 1.56 (1.32–1.87)] but not increasing LAmax/BSA [HR per 1 SD (8.6 mL/m2): 1.14 (0.97–1.34)] was independently associated with mortality. Furthermore, the addition of LAEF to a model adjusting Framingham risk score, diabetes, race, LV mass, and ejection fraction improved the c-statistic (c-statistics: 0.78 vs. 0.77; P < 0.05, respectively), whereas the addition of LAmax/BSA did not (c-statistics: 0.76, P = 0.20).
In the general population, both LAmax/BSA and LAEF are important subclinical phenotypes but LAEF is superior and incremental to LAmax/BSA.
Left atrial volume index; Left atrial systolic function; Population
Considerable excitement and interest have arisen recently concerning the role that acute emotional triggers may play in precipitating a myocardial infarction (MI). Observational studies have found repeatedly that patients report excessive anger, anxiety, sadness, grief, or acute stress immediately prior to onset of MI, and recent meta-analyses summarizing these findings reported strong associations between MI occurrence and many of these acute emotions. However, it is unclear whether and through what mechanisms acute emotional triggers might influence MI, and whether there is any clinical utility in knowing if or how emotions trigger MI. We debate whether emotional triggers matter by reviewing the recent evidence for the association between acute emotional triggers and MI and by describing the potential pathophysiological characteristics and mechanisms underlying this association and the preventive strategies that could be used to mitigate the risk of acute MI. We also examine whether the study of emotional triggers could influence clinical risk management or changes in clinical practice/management. We offer suggestions for research that might shed light on whether emotional triggers could initiate a paradigm shift in preventive cardiology, or whether acute emotional triggers are either intractable catalysts for, or merely an epiphenomenon of, some MIs.
Myocardial infarction; Emotional triggers; Risk factors; Epidemiology
The Surgical Treatment for Ischemic Heart Failure (STICH) trial demonstrated no overall benefit when surgical ventricular reconstruction (SVR) was added to coronary artery bypass grafting (CABG) in patients with ischaemic cardiomyopathy. The present analysis was to determine whether, based on baseline left ventricular (LV) function parameters, any subgroups could be identified that benefited from SVR.
Methods and results
Among the 1000 patients enrolled, Core Lab measures of baseline LV function with adequate quality were obtained in 710 patients using echocardiography, in 352 using cardiovascular magnetic resonance, and in 344 using radionuclide imaging. The relationship between LV end-systolic volume index (ESVI), end-diastolic volume index, ejection fraction (EF), regional wall motion abnormalities, and outcome were first assessed only by echocardiographic measures, and then by 13 algorithms using a different hierarchy of imaging modalities and their quality. The median ESVI and EF were 78.0 (range: 22.8–283.8) mL/m2 and 28.0%, respectively. Hazard ratios comparing the randomized arms by subgroups of LVESVI and LVEF measured by echocardiography found that patients with smaller ventricles (LVESVI <60 mL/m2) and better LVEF (≥33%) may have benefitted by SVR, while those with larger ventricles (LVESVI >90 mL/m2) and lower LVEF (≤25%) did worse with SVR. Algorithms using all three imaging modalities found a weaker relationship between LV global function and the effects of SVR. The extent of regional wall motion abnormality did not influence the effects of SVR.
Subgroup analyses of the STICH trial suggest that patients with less dilated LV and better LVEF may benefit from SVR, while those with larger LV and poorer LVEF may do worse.
Clinical Trial Registration #: NCT00023595.
STICH; Surgical ventricular reconstruction; Coronary disease; Heart failure
There are limited contemporary data on the presentation, management, and outcomes of acute coronary syndrome (ACS) admissions in India. We aimed to develop a prospective registry to address treatment and health systems gaps in the management of ACSs in Kerala, India.
Methods and results
We prospectively collected data on 25 748 consecutive ACS admissions from 2007 to 2009 in 125 hospitals in Kerala. We evaluated data on presentation, management, and in-hospital mortality and major adverse cardiovascular events (MACE). We created random-effects multivariate regression models to evaluate predictors of outcomes while accounting for confounders. Mean (SD) age at presentation was 60 (12) years and did not differ among ACS types [ST-segment myocardial infarction (STEMI) = 37%; non-STEMI = 31%; unstable angina = 32%]. In-hospital anti-platelet use was high (>90%). Thrombolytics were used in 41% of STEMI, 19% of non-STEMI, and 11% of unstable angina admissions. Percutaneous coronary intervention rates were marginally higher in STEMI admissions. Discharge medication rates were variable and generally suboptimal (<80%). In-hospital mortality and MACE rates were highest for STEMI (8.2 and 10.3%, respectively). After adjustment, STEMI diagnosis (vs. unstable angina) [odds ratio (OR) (95% confidence interval = 4.06 (2.36, 7.00)], symptom-to-door time >6 h [OR = 2.29 (1.73, 3.02)], and inappropriate use of thrombolysis [OR = 1.33 (0.92, 1.91)] were associated with higher risk of in-hospital mortality and door-to-needle time <30 min [OR = 0.44 (0.27, 0.72)] was associated with lower mortality. Similar trends were seen for risk of MACE.
These data represent the largest ACS registry in India and demonstrate opportunities for improving ACS care.
Acute coronary syndrome; India; Registry; Outcomes
Drug-induced Torsades de Pointes is a rare, unpredictable, and life-threatening serious adverse event. It can be caused by both cardiac and non-cardiac drugs and has become a major issue in novel drug development and for the regulatory authorities. This review describes the problem, predisposing factors, and the underlying genetic predisposition as it is understood currently. The future potential for pharmacogenomic-guided and personalized prescription to prevent drug-induced Torsades de Pointes is discussed. Database searches utilized reports from www.qtdrugs.org up to January 2012, case reports and articles from www.pubmed.com up to January 2012, and the British National Formulary edition at www.bnf.org.
Torsades de pointes; Serious adverse events; Anti-arrhythmic drugs; Pharmacogenomics; Drug-induced arrhythmia; Acquired long QT syndrome
The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke.
Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden.
Design, setting, and patients
A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed.
During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3–14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22–3.64, P = 0.008).
Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment.
Atrial fibrillation; Anticoagulation; Implantable defibrillator; Pacemaker; Stroke
Interleukin-7 (IL-7) is a master regulator of T-cell development and homoeostasis. Increased IL-7 levels are associated with inflammatory diseases. The aims of this study were to determine whether IL-7 is a biomarker for inflammatory conditions or an active participant in atherogenesis.
Methods and results
Advanced atherosclerotic lesions in Apoe−/− mice were regressed by long-term cholesterol lowering through treatment with a helper-dependent adenovirus expressing apolipoprotein E (n= 6–10). Using this model, gene expression patterns in the aorta were analysed at an early phase of regression by microarray. After stringent statistical analysis, we found that IL-7 expression is significantly reduced in response to lowering of cholesterol (n= 6). To understand the importance of IL-7 down-regulation for atherosclerotic regression, we studied the effects and mechanisms of action of IL-7 on endothelial cells (ECs) in vitro as well as in vivo. Our major findings are: (i) IL-7 up-regulates cell adhesion molecules and monocyte chemoattractant protein-1 in ECs and promotes monocyte adhesion to ECs; (ii) this regulation is mediated by phosphatidylinositol 3-kinase (PI3K)/AKT-dependent and -independent activation of NF-κB; (iii) elevation of plasma IL-7 induces recruitment of monocytes/macrophages to endothelium without affecting plasma cholesterol (n= 5, 6); and (4) lack of IL-7 in bone marrow-derived cells reduces migration of monocytes/macrophages to the lesions (n= 5, 6).
These results suggest that IL-7 inflames endothelium via PI3K/AKT-dependent and -independent activation of NF-κB and recruits monocytes/macrophages to the endothelium, thus playing an active role in atherogenesis.
Atherosclerosis; Cell adhesion molecules; Chemokine; Endothelium
To date, the therapeutic benefit of revascularization vs. medical therapy for stable individuals undergoing invasive coronary angiography (ICA) based upon coronary computed tomographic angiography (CCTA) findings has not been examined.
Methods and results
We examined 15 223 patients without known coronary artery disease (CAD) undergoing CCTA from eight sites and six countries who were followed for median 2.1 years (interquartile range 1.4–3.3 years) for an endpoint of all-cause mortality. Obstructive CAD by CCTA was defined as a ≥50% luminal diameter stenosis in a major coronary artery. Patients were categorized as having high-risk CAD vs. non-high-risk CAD, with the former including patients with at least obstructive two-vessel CAD with proximal left anterior descending artery involvement, three-vessel CAD, and left main CAD. Death occurred in 185 (1.2%) patients. Patients were categorized into two treatment groups: revascularization (n = 1103; 2.2% mortality) and medical therapy (n = 14 120, 1.1% mortality). To account for non-randomized referral to revascularization, we created a propensity score developed by logistic regression to identify variables that influenced the decision to refer to revascularization. Within this model (C index 0.92, χ2 = 1248, P < 0.0001), obstructive CAD was the most influential factor for referral, followed by an interaction of obstructive CAD with pre-test likelihood of CAD (P = 0.0344). Within CCTA CAD groups, rates of revascularization increased from 3.8% for non-high-risk CAD to 51.2% high-risk CAD. In multivariable models, when compared with medical therapy, revascularization was associated with a survival advantage for patients with high-risk CAD [hazards ratio (HR) 0.38, 95% confidence interval 0.18–0.83], with no difference in survival for patients with non-high-risk CAD (HR 3.24, 95% CI 0.76–13.89) (P-value for interaction = 0.03).
In an intermediate-term follow-up, coronary revascularization is associated with a survival benefit in patients with high-risk CAD by CCTA, with no apparent benefit of revascularization in patients with lesser forms of CAD.
Computed tomography; Coronary revascularization; Medical therapy; Coronary artery disease
For the characterization of endothelial progenitor cells (EPCs), commonly the markers CD34 and KDR have been used. CD133+/CD34−/KDR+ cells may represent more immature ‘early’ progenitors. In patients with coronary artery disease (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN), which may mediate vascular calcification and abnormal repair. The aim of this study was to evaluate the expression of OCN+ ‘early’ EPCs in patients with risk factors (RFs) and a history of stable (history of stenting/coronary artery bypass grafting) or unstable CAD (myocardial infarction).
Methods and results
Medical history and blood samples from 282 patients (age 58 ± 16 years) with CAD or at least one RF (mean 2.5 ± 1.5) were analysed. For the analysis of EPC markers (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear cells was performed. Circulating OCN+/CD133+/CD34−/KDR+ cells (median counts [interquartile range] per 100 000 events) were 15 [4–41] in patients with RF (n = 199), 26 [1–136] in those with a history of stable (n = 57), and 246 [105–308] in those with a history of unstable CAD (n = 26; P < 0.001). The association with unstable CAD remained highly significant even after multivariate adjusting for RFs and the different characteristics of the groups. Osteocalcin positive ‘early’ EPCs trend to predict further events [HR for each doubling of the cell number: 1.20 (95% CI: 1.00–1.46), P = 0.06].
Circulating OCN+ ‘early’ EPCs are strongly associated with unstable CAD. Therefore, this particular subset of EPCs could mediate abnormal vascular repair and may help identifying patients with a more unstable phenotype of atherosclerosis.
Coronary artery disease; Arthrosclerosis; Endothelial progenitor cells; Marker; Osteocalcin
The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 µg/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF).
Methods and results
This double-blind, multicentre study randomized 71 AHF patients with pulmonary capillary wedge pressure (PCWP) ≥18 mmHg, systolic blood pressure (BP) ≥115 mmHg, and estimated glomerular filtration rate ≥30 mL/min/1.73 m2 to serelaxin (n = 34) or placebo (n = 37) within 48 h of hospitalization. Co-primary endpoints were peak change from baseline in PCWP and cardiac index (CI) during the first 8 h of infusion. Among 63 patients eligible for haemodynamic analysis (serelaxin, n = 32; placebo, n = 31), those treated with serelaxin had a significantly higher decrease in peak PCWP during the first 8 h of infusion (difference vs. placebo: −2.44 mmHg, P = 0.004). Serelaxin showed no significant effect on the peak change in CI vs. placebo. Among secondary haemodynamic endpoints, a highly significant reduction in pulmonary artery pressure (PAP) was observed throughout the serelaxin infusion (largest difference in mean PAP vs. placebo: −5.17 mmHg at 4 h, P < 0.0001). Right atrial pressure, systemic/pulmonary vascular resistance, and systolic/diastolic BP decreased from baseline with serelaxin vs. placebo and treatment differences reached statistical significance at some time points. Serelaxin administration improved renal function and decreased N-terminal pro-brain natriuretic peptide levels vs. placebo. Treatment with serelaxin was well tolerated with no apparent safety concerns.
The haemodynamic effects of serelaxin observed in the present study provide plausible mechanistic support for improvement in signs and symptoms of congestion observed with this agent in AHF patients.
ClinicalTrials.gov identifier NCT01543854.
Serelaxin; Acute heart failure; Haemodynamics; Clinical trial
Because benefits of cardiac resynchronization therapy (CRT) appear to be less favourable in non-left bundle branch block (LBBB) patients, this prospective longitudinal study tested the hypothesis that QRS morphology and echocardiographic mechanical dyssynchrony were associated with long-term outcome after CRT.
Methods and results
Two-hundred and seventy-eight consecutive New York Heart Association class III and IV CRT patients with QRS ≥120 ms and ejection fraction ≤35% were studied. The pre-specified primary endpoint was death, heart transplant, or left ventricular assist device over 4 years. Dyssynchrony assessed before CRT included interventricular mechanical delay (IVMD) and speckle-tracking radial strain using pre-specified cut-offs for each. Of 254 with baseline quantitative echocardiographic data available, 128 had LBBB, 81 had intraventricular conduction delay (IVCD), and 45 had right bundle branch block (RBBB). Radial dyssynchrony was observed in 85% of the patients with LBBB, 59% with IVCD*, and 40% with RBBB* (*P < 0.01 vs. LBBB). Of 248 (98%) with follow-up, LBBB patients had a significantly more favourable long-term survival than non-LBBB patients. However, non-LBBB patients with dyssynchrony had a more favourable event-free survival than those without dyssynchrony: radial dyssynchrony hazard ratio 2.6, 95% confidence interval (CI) 1.47–4.53 (P = 0.0008) and IVMD hazard ratio 4.9, 95% CI 2.60–9.16 (P = 0.0007). Right bundle branch block patients who lacked dyssynchrony had the least favourable outcome.
Non-LBBB patients with dyssynchrony had a more favourable long-term survival than non-LBBB patients who lacked dyssynchrony. Mechanical dyssynchrony and QRS morphology are associated with outcome following CRT.
Cardiac resynchronization therapy; Heart failure; Conduction disturbance
Far more extensive than the epicardial coronary vasculature that can be visualized angiographically is the coronary microcirculation, which foregoes routine imaging. Probably due to the lack of techniques able to provide tangible evidence of its crucial role, the clinical importance of coronary microvascular dysfunction is not fully appreciated. However, evidence gathered over the last several decades indicates that both functional and structural abnormalities of the coronary microvasculature can lead to myocardial ischaemia, often comparable with that caused by obstructive coronary artery disease. Indeed, a marked increase in coronary microvascular resistance can impair coronary blood flow and trigger angina pectoris, ischaemic ECG shifts, and myocardial perfusion defects, and lead to left ventricular dysfunction in patients who otherwise have patent epicardial coronary arteries. This condition—often referred to as ‘chest pain with normal coronary arteries’ or ‘cardiac syndrome X’—encompasses several pathogenic mechanisms involving the coronary microcirculation. Of importance, coronary microvascular dysfunction can occur in conjunction with several other cardiac disease processes. In this article, we review the pathogenic mechanisms leading to coronary microvascular dysfunction and its diagnostic assessment, as well as the different clinical presentations and prognostic implications of microvascular angina. As such, this review aims to remove at least some of the mystery surrounding the notion of coronary microvascular dysfunction and to show why it represents a true clinical entity.
Cardiac syndrome X; Coronary flow reserve; Microvascular angina; Prognosis
Atrial fibrillation (AF) is the most common sustained arrhythmia. Increased body size has been associated with AF, but the relationship is not well understood. In this study, we examined the effect of increased height on the risk of AF and explore potential mediators and implications for clinical practice.
Methods and results
We examined data from 5860 individuals taking part in the Cardiovascular Health Study, a cohort study of older US adults followed for a median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age-stratified Cox proportional hazards and risk models were used, with focus on the effect of height on both prevalent and incident AF. Among 684 (22.6%) and 568 (27.1%) incident cases in women and men, respectively, greater height was significantly associated with AF risk [hazard ratio (HR)women per 10 cm 1.32, confidence interval (CI) 1.16–1.50, P < 0.0001; HRmen per 10 cm 1.26, CI 1.11–1.44, P < 0.0001]. The association was such that the incremental risk from sex was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32–1.65, without height, and HR 0.94, CI 0.85–1.20, with height included). Inclusion of height in the Framingham model for incident AF improved discrimination. In sequential models, however, we found minimal attenuation of the risk estimates for AF with adjustment for left ventricular (LV) mass and left atrial (LA) dimension. The associations of LA and LV size measurements with AF risk were weakened when indexed to height.
Independent from sex, increased height is significantly associated with the risk of AF.
Atrial fibrillation; Cardiovascular risk factors; Echocardiography; Risk prediction
Current interventional procedures in structural heart disease and cardiac arrhythmias require peri-interventional echocardiographic monitoring and guidance to become as safe, expedient, and well-tolerated for patients as possible. Intracardiac echocardiography (ICE) complements and has in part replaced transoesophageal echocardiography (TEE), including real-time three-dimensional (RT-3D) imaging. The latter is still widely accepted as a method to prepare for and to guide interventional treatments. In contrast to TEE, ICE represents a purely intraprocedural guiding and imaging tool unsuitable for diagnostic purposes. Patients tolerate ICE much better, and the method does not require general anaesthesia. Accurate imaging of the particular pathology, its anatomic features, and spatial relation to the surrounding structures is critical for catheter and wire positioning, device deployment, evaluation of the result, and for ruling out complications. This review describes the peri-interventional role of ICE, outlines current limitations, and points out future implications. Two-dimensional ICE has become a suitable guiding tool for a variety of percutaneous treatments in patients who are conscious or under monitored anaesthesia care, whereas RT-3DICE is still undergoing clinical testing. Continuous TEE monitoring under general anaesthesia remains a widely accepted alternative.
Intracardiac echocardiography; Structural heart disease; Peri-interventional imaging; Guiding tools
Catheter ablation (CA) is a highly effective therapy for the treatment of paroxysmal atrial fibrillation (AF) when compared with antiarrhythmic drug therapy (ADT). No randomized studies have compared the two strategies in persistent AF. The present randomized trial aimed to compare the effectiveness of CA vs. ADT in treating persistent AF.
Methods and results
Patients with persistent AF were randomly assigned to CA or ADT (excluding patients with long-standing persistent AF). Primary endpoint at 12-month follow-up was defined as any episode of AF or atrial flutter lasting >24 h that occurred after a 3-month blanking period. Secondary endpoints were any atrial tachyarrhythmia lasting >30 s, hospitalization, and electrical cardioversion. In total, 146 patients were included (aged 55 ± 9 years, 77% male). The ADT group received class Ic (43.8%) or class III drugs (56.3%). In an intention-to-treat analysis, 69 of 98 patients (70.4%) in the CA group and 21 of 48 patients (43.7%) in the ADT group were free of the primary endpoint (P = 0.002), implying an absolute risk difference of 26.6% (95% CI 10.0–43.3) in favour of CA. The proportion of patients free of any recurrence (>30 s) was higher in the CA group than in the ADT group (60.2 vs. 29.2%; P < 0.001) and cardioversion was less frequent (34.7 vs. 50%, respectively; P = 0.018).
Catheter ablation is superior to medical therapy for the maintenance of sinus rhythm in patients with persistent AF at 12-month follow-up.
Clinical Trial Registration Information
Atrial fibrillation; Catheter ablation; Antiarrhythmic drug; Atrial flutter; Clinical trial
The evolution of reperfusion therapy in acute myocardial infarction and acute ischaemic stroke has many similarities: thrombolysis is superior to placebo, intra-arterial thrombolysis is not superior to intravenous (i.v.), facilitated intervention is of questionable value, and direct mechanical recanalization without thrombolysis is proven (myocardial infarction) or promising (stroke) to be superior to thrombolysis—but only when started with no or minimal delay. However, there are also substantial differences. Direct catheter-based thrombectomy in acute ischaemic stroke is more difficult than primary angioplasty (in ST-elevation myocardial infarction [STEMI]) in many ways: complex pre-intervention diagnostic workup, shorter time window for clinically effective reperfusion, need for an emergent multidisciplinary approach from the first medical contact, vessel tortuosity, vessel fragility, no evidence available about dosage and combination of peri-procedural antithrombotic drugs, risk of intracranial bleeding, unclear respective roles of thrombolysis and mechanical intervention, lower number of suitable patients, and thus longer learning curves of the staff. Thus, starting acute stroke interventional programme requires a lot of learning, discipline, and humility. Randomized trials comparing different reperfusion strategies provided similar results in acute ischaemic stroke as in STEMI. Thus, it might be expected that also a future randomized trial comparing direct (primary) catheter-based thrombectomy vs. i.v. thrombolysis could show superiority of the mechanical intervention if it would be initiated without delay. Such randomized trial is needed to define the role of mechanical intervention alone in acute stroke treatment.
Myocardial infarction; Acute stroke; Reperfusion; Thrombolysis; Primary angioplasty; Catheter intervention; Thrombectomy
To assess the impact of relief of pulmonary stenosis (PS) and pulmonary regurgitation (PR) by percutaneous pulmonary valve implantation (PPVI) on biventricular function during exercise stress.
Methods and results
Seventeen patients, who underwent PPVI for PS or PR, were included. Magnetic resonance imaging was performed at rest and during supine exercise stress pre- and within 1-month post-PPVI, using a radial k − t SENSE real-time sequence. In patients with PS (n = 9), there was no reserve in right ventricular (RV) ejection fraction (EF) in response to exercise prior to PPVI (48.2 ± 12.1% at rest vs. 48.4 ± 14.8% during exercise, P = 0.87). Post-PPVI, reserve in RVEF in response to exercise was re-established (53.4 ± 15.0% at rest vs. 59.6 ± 17.3% during exercise, P = 0.003) with improvement in left ventricular stroke volume (LVSV) (45.4 ± 6.2 mL/m2 at rest vs. 52.8 ± 8.8 mL/m2 during exercise, P = 0.001). In patients with PR prior to PPVI (n = 8), LVSV during exercise increased (43.0 ± 8.5 vs. 54.3 ± 6.6 mL/m2, P < 0.001) due to reduction in PR fraction during exercise (29.2 ± 5.2 vs. 13.6 ± 6.1%, P < 0.001). After PPVI, LVSV increased from rest to exercise (48.4 ± 8.8 vs. 57.2 ± 8.1 mL/m2, P < 0.001) due to improved RVEF (45.5 ± 8.3 vs. 50.4 ± 6.9%, P = 0.001). There was a significantly higher increase in LVSV at exercise from pre- to post-PPVI in PS patients than in PR patients (ΔLVSV 8.2 ± 4.1 vs. Δ2.9 ± 4.1 mL/m2, P = 0.01). The reduction in the RV outflow tract gradient correlated significantly with the improvement in LVSV during exercise (r = −0.73, P < 0.001).
Percutaneous pulmonary valve implantation in patients with PS leads to restoration of reserve in RVEF during exercise stress. In patients with PR, SV augmentation improves only mildly post-PPVI. Improvement in SV augmentation during exercise stress after PPVI is dependent mainly on afterload reduction.
Exercise physiology; Right ventricular outflow tract dysfunction; Percutaneous pulmonary valve implantation; Congenital heart disease; Exercise stress magnetic resonance imaging