Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation.

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

Sex differences in transaortic flow rate and association with all-cause mortality in patients with severe aortic stenosis.

AIMS: It is not known whether transaortic flow rate (FR) in aortic stenosis (AS) differs between men and women, and whether the commonly used cut-off of 200 mL/s is prognostic in females. We aimed to explore sex differences in the determinants of FR, and determine the best sex-specific cut-offs for prediction of all-cause mortality. METHODS AND RESULTS: Between 2010 and 2017, a total of 1564 symptomatic patients (mean age 76 ± 13 years, 51% men) with severe AS were prospectively included. Mean follow-up was 35 ± 22 months. The prevalence of cardiovascular disease was significantly higher in men than women (63% vs. 42%, P < 0.001). Men had higher left ventricular mass and lower left ventricular ejection fraction compared to women (both P < 0.001). Men were more likely to undergo an aortic valve intervention (AVI) (54% vs. 45%, P = 0.001), while the death rates were similar (42.0% in men and 40.6% in women, P = 0.580). A total of 779 (49.8%) patients underwent an AVI in which 145 (18.6%) died. In a multivariate Cox regression analysis, each 10 mL/s decrease in FR was associated with a 7% increase in hazard ratio (HR) for all-cause mortality (HR 1.07; 95% CI 1.03-1.11, P < 0.001). The best cut-off value of FR for prediction of all-cause mortality was 179 mL/s in women and 209 mL/s in men. CONCLUSION: Transaortic FR was lower in women than men. In the group undergoing AVI, lower FR was associated with increased risk of all-cause mortality, and the optimal cut-off for prediction of all-cause mortality was lower in women than men.

Reversible exercise-induced left ventricular dysfunction in symptomatic patients with previous Takotsubo syndrome: insights from stress echocardiography.

AIMS: Takotsubo syndrome (TTS) is usually associated with rapid and spontaneous recovery of left ventricular (LV) function. However, a proportion of patients may have persistent symptoms. This study aimed to determine the haemodynamic and LV contractile responses to exercise in these patients. METHODS AND RESULTS: Thirty symptomatic TTS patients referred for exercise echocardiography, a median of 15 months following the index TTS episode, were matched with 30 controls with normal exercise echocardiography. Beta-blockers were withheld prior to the test. LV volumes, ejection fraction (EF) and wall motion score index (WMSI), were measured at rest and stress. The TTS cohort were Caucasian women with mean age of 64.6 ± 7.4 years and similar coronary risk factor profile and EF to controls. Resting systolic blood pressure (SBP), LV end-diastolic volume, wall stress, and right ventricular fractional area change were higher in TTS patients compared with controls. Stress echo data showed similar exercise time, peak heart rate, and peak SBP in TTS patients vs. controls, but TTS patients had higher LV volumes, lower exercise LVEF (70 ± 10% vs. 78 ± 7%; P = 0.001), ΔLVEF (4 ± 8% vs. 12 ± 5%; P < 0.001), and WMSI (1.4 ± 0.4 vs. 1 ± 0; P < 0.001) compared with controls. Twenty TTS patients had clear exercise-induced wall motion abnormalities, mainly involving the apex or more globally, with a mean ΔLVEF of 1% compared with 12% in controls. Among the other 10 TTS patients, the ΔLVEF was 10%. CONCLUSION: Symptomatic patients with previous TTS have a blunted contractile response to exercise. The therapeutic and prognostic implications of these findings need further investigation.

Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial.

AIMS: Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. METHODS AND RESULTS: We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). CONCLUSION: Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. CLINICAL TRIAL REGISTRATION: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688.

Long-Term Prognostic Value of Simultaneous Assessment of Atherosclerosis and Ischemia in Patients with Suspected Angina: Implications for Routine Use of Carotid Ultrasound during Stress Echocardiography.

BACKGROUND: While the impact of carotid plaque on cardiovascular events is well investigated in asymptomatic epidemiologic studies, the long-term clinical impact of carotid plaque and its burden (CPB) in patients with new-onset suspected stable angina with no history of coronary artery disease beyond stress echocardiography (SE) is not known. We sought to investigate this with a prospective study, where patients were followed up for adverse events. METHODS: Consecutive patients referred for SE underwent simultaneous carotid ultrasonography to assess CPB, defined as the total number of carotid plaques per patient. Stress echocardiography was reported off-line using a 17-segments model and four-point wall thickening scoring. Peak wall thickening scoring index was the sum of scores of each segment divided by 17. RESULTS: Of the 592 patients, 573 (age 59 ± 11, 45% male) had follow-up data. During a mean of 7.2 years, 85 patients had a first major adverse event (all-cause mortality and acute myocardial infarction: 68 had hard events and 17 had unplanned revascularization). On multivariate Cox regression analysis, pretest probability of coronary artery disease (P = .048), peak wall thickening scoring index (P < .0001), and CPB (P < .0001) predicted major adverse events; however, only CPB retained significance for both hard events and hard cardiac events (P = .001 and < .0001, respectively). Major adverse events and hard events were the least in patients with normal SE and absent carotid plaque (annualized event rate: 1.1% and 1.02%, respectively), with a significant increase in normal SE and carotid plaque disease (2.4% and 2.05%, P = .004 and P = .01, respectively). The presence of plaque did not have an impact on these outcomes in an abnormal SE cohort. CONCLUSIONS: In patients with suspected stable angina with no history of cardiovascular disease, carotid atherosclerosis and myocardial ischemia detected by ultrasound provided synergistic information for the long-term prediction of events, but atherosclerosis predicted hard events beyond myocardial ischemia, particularly in patients with a normal SE.

Assessment of Complex Multi-Valve Disease and Prosthetic Valves.

Multivalvular heart disease (MVD) is a highly prevalent condition causing significant morbidity and mortality. The complex haemodynamic interactions between coexisting valve lesions makes the diagnosis and treatment challenging. Current guidelines may not be adequate for managing the varying clinical scenarios of MVD and, therefore, the expertise of a multidisciplinary Heart Valve Team is of paramount importance. The indications for intervention should be based on a global assessment of the consequences of the multiple valve lesions after a careful estimation of the added surgical risk of combined procedures, the long-term risk of morbidity and mortality associated with multiple valve prostheses and the risk of reoperation if less-than-severe valve lesions are left untreated at the time of first evaluation. Echocardiography plays an important role in assessing patients and, as a general rule, an accurate echo diagnosis needs to combine different measurements. The emerging transcatheter valve therapies should be considered an option for high risk patients. More data on the natural history of MVD and the impact of intervention on outcome are required to better define the optimal management strategy.

Activity and outcomes of a cardio-oncology service in the United Kingdom-a five-year experience.

AIMS: Cardio-oncology clinics optimise the cardiovascular status of cancer patients but there is a limited description of their structure, case mix, activity and results. The purpose of this paper is to describe the activity and outcomes of a cardio-oncology service, particularly with respect to supporting optimal cancer treatment and survival. METHODS AND RESULTS: We prospectively studied patients referred to our service from February 2011 to February 2016. New York Heart Association (NYHA) class and parameters of cardiac function were measured at baseline and after optimisation by our service. Up-titration of cardiac treatment, continuation of cancer therapy and mortality were used as outcome measures. Of the 535 patients (55.8% females) referred, rates of cardiotoxicity for anthracyclines, anti-HER2 agents and tyrosine kinase inhibitors were 75.8%, 69.8% and 62.1%, respectively. Patients with left ventricular systolic dysfunction (LVSD) (n =128) were younger, had higher rates of hypertension and previous exposure to chemotherapy/radiotherapy (P < 0.001). At a median follow-up of 360 days, 93.8% of the patients with LVSD showed improvement in left ventricular ejection fraction (45% pre vs. 53% post; P < 0.001) and NYHA class (NYHA III-IV in 22% pre vs. 10% post; P = 0.01). All patients with normal left ventricular ejection fraction and biochemical or functional myocardial toxicity and 88% of patients with LVSD were deemed fit for continuation of cancer therapy after cardiovascular optimisation. CONCLUSIONS: Through the establishment of a cardio-oncology service, it is feasible to achieve high rates of cardiac optimisation and cancer treatment continuation.

Cardio-oncology: the role of advanced echocardiography in cancer patients.

INTRODUCTION: Cardio-oncology is a rapidly growing field aimed at improving the quality of care of cancer patients by preventing and monitoring cardiovascular complications resulting from cancer treatment. Cardiac imaging, and in particular, transthoracic echocardiography, plays an essentialrole in the baseline assessment and serial follow-up of cardio-oncology patients. Areas covered: This review article discusses the role of cardiac imaging with a focus on advanced echocardiography for the detection and management of cancer therapy related cardiovascular complications, in particular, left ventricular dysfunction and heart failure. Expert commentary: While traditional imaging based assessment of left ventricular ejection fraction still has its place in cardiac monitoring, more advanced echocardiographic modalities, in particular, myocardial deformation imaging with speckle tracking strain analysis, show great potential for detecting early signs of cardiotoxicity. Larger studies are needed to determine both the clinical role of strain measurement in influencing initiation of cardioprotective agents and its prognostic value in long term outcome.

Incidental finding of a double orifice mitral valve in an elderly patient: value of 3D imaging.

A rare isolated double orifice mitral valve (DOMV) was diagnosed in a 77-year-old male patient, being assessed for surgical repair of the ascending aorta. This is a rare congenital abnormality, usually discovered as an incidental finding during investigation of other congenital heart defects. This case shows that a detailed assessment of all cardiac structures is necessary, not only in young patients, but also in the elderly population, to minimise the under-diagnosis of such rare anomalies. The use of 3D transthoracic echocardiography (TTE) has an increasingly significant role in establishing the diagnosis and extending the morphological and functional understanding of the anomaly. LEARNING POINTS: Thoroughly assessing all cardiac structures, in accordance with the minimum dataset guidelines for transthoracic echocardiography, ensures not only a comprehensive assessment of the primary indication for the scan, but also improves the detection of concomitant and otherwise unknown lesions. Despite falling under the category of congenital heart defects, several rare anomalies such as DOMV can be present in elderly patients, and the adult echocardiographer should have appropriate knowledge and awareness for detecting these conditions. 3D TTE provides a comprehensive assessment of the morphology of DOMV, over and above the information obtained by 2D imaging.

Effects of renal denervation on vascular remodelling in patients with heart failure and preserved ejection fraction: A randomised control trial.

OBJECTIVE: To assess the effect of renal denervation (RDT) on micro- and macro-vascular function in patients with heart failure with preserved ejection fraction (HFpEF). DESIGN: A prospective, randomised, open-controlled trial with blinded end-point analysis. SETTING: A single-centre London teaching hospital. PARTICIPANTS: Twenty-five patients with HFpEF who were recruited into the RDT-PEF trial. MAIN OUTCOME MEASURES: Macro-vascular: 24-h ambulatory pulse pressure, aorta distensibilty (from cardiac magnetic resonance imaging (CMR), aorta pulse wave velocity (CMR), augmentation index (peripheral tonometry) and renal artery blood flow indices (renal MR). Micro-vascular: endothelial function (peripheral tonometry) and urine microalbuminuria. RESULTS: At baseline, 15 patients were normotensive, 9 were hypertensive and 1 was hypotensive. RDT did not lower any of the blood pressure indices. Though there was evidence of abnormal vascular function at rest, RDT did not affect these at 3 or 12 months follow-up. CONCLUSIONS: RDT did not improve markers of macro- and micro-vascular function.

Simultaneous Assessment of Myocardial Perfusion, Wall Motion, and Deformation during Myocardial Contrast Echocardiography: A Feasibility Study.

AIMS: Ultrasound contrast agents may be used for the assessment of regional wall motion and myocardial perfusion, but are generally considered not suitable for deformation analysis. The aim of our study was to assess the feasibility of deformation imaging on contrast-enhanced images using a novel methodology. METHODS AND RESULTS: We prospectively enrolled 40 patients who underwent stress echocardiography with continuous intravenous infusion of SonoVue for the assessment of myocardial perfusion imaging with flash replenishment technique. We compared longitudinal strain (Lε) values, assessed with a vendor-independent software (2D CPA), on 68 resting contrast-enhanced and 68 resting noncontrast recordings. Strain analysis on contrast recordings was evaluated in the first cardiac cycles after the flash. Tracking of contrast images was deemed feasible in all subjects and in all views. Contrast administration improved image quality and increased the number of segments used for deformation analysis. Lε of noncontrast and contrast-enhanced images were statistically different (-18.8 ± 4.5% and -22.8 ± 5.4%, respectively; P < 0.001), but their correlation was good (ICC 0.65, 95%CI 0.42-0.78). Patients with resting wall-motion abnormalities showed lower Lε values on contrast recordings (-18.6 ± 6.0% vs. -24.2 ± 5.5%, respectively; P < 0.01). Intra-operator and inter-operator reproducibility was good for both noncontrast and contrast images with no statistical differences. CONCLUSIONS: Our study shows that deformation analysis on postflash contrast-enhanced images is feasible and reproducible. Therefore, it would be possible to perform a simultaneous evaluation of wall-motion abnormalities, volumes, ejection fraction, perfusion defects, and cardiac deformation on the same contrast recording.