Yun Yun Go

Echocardiographic reference ranges for normal left ventricular 2D strain: results from the EACVI NORRE study

AimsnTo obtain the normal ranges for 2D echocardiographic (2DE) measurements of left ventricular (LV) strain from a large group of healthy volunteers accounting for age and gender.nnnMethods and resultsnA total of 549 (mean age: 45.6u2009±u200913.3u2009years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. 2DE data sets have been analysed with a vendor-independent software package allowing homogeneous measurements irrespective of the echocardiographic equipment used to acquire the data sets. The lowest expected values of LV strains and twist calculated asu2009±u20091.96 standard deviations from the mean were -16.7% in men and -17.8% in women for longitudinal strain, -22.3% and -23.6% for circumferential strain, 20.6% and 21.5% for radial strain, and 2.2 degrees and 1.9 degrees for twist, respectively. In multivariable analysis, longitudinal strain decreased with age whereas the opposite occurred with circumferential and radial strain. Male gender was associated with lower strain for longitudinal, circumferential, and radial strain. Inter-vendor differences were observed for circumferential and radial strain despite the use of vendor-independent software. Importantly, no intervendor differences were noted in longitudinal strain.nnnConclusionnThe NORRE study provides contemporary, applicable 2D echocardiographic reference ranges for LV longitudinal, radial, and circumferential strain. Our data highlight the importance of age- and gender-specific reference values for LV strain.

Echocardiographic reference ranges for normal left atrial function parameters: results from the EACVI NORRE study

AimsnTo obtain the normal ranges for echocardiographic measurements of left atrial (LA) function from a large group of healthy volunteers accounting for age and gender.nnnMethods and resultsnA total of 371 (median age 45u2009years) healthy subjects were enrolled at 22 collaborating institutions collaborating in the Normal Reference Ranges for Echocardiography (NORRE) study of the European Association of Cardiovascular Imaging (EACVI). Left atrial data sets were analysed with a vendor-independent software (VIS) package allowing homogeneous measurements irrespective of the echocardiographic equipment used to acquire data sets. The lowest expected values of LA function were 26.1%, 48.7%, and 41.4% for left atrial strain (LAS), 2D left atrial emptying fraction (LAEF), and 3D LAEF (reservoir function); 7.7%, 24.2%, and -0.53/s for LAS-active, LAEF-active, and LA strain rate during LA contraction (SRa) (pump function) and 12.0% and 21.6% for LAS-passive and LAEF-passive (conduit function). Left atrial reservoir and conduit function were decreased with age while pump function was increased. All indices of reservoir function and all LA strains had no difference in both gender and vendor. However, inter-vendor differences were observed in LA SRa despite the use of VIS.nnnConclusionnThe NORRE study provides contemporary, applicable echocardiographic reference ranges for LA function. Our data highlight the importance of age-specific reference values for LA functions.

Secondary tricuspid regurgitation in patients with left ventricular systolic dysfunction: cause for concern or innocent bystander?

Secondary (functional) tricuspid regurgitation (TR) has long been neglected and regarded not so much as a genuine problem, but as a surrogate of a more fundamental condition. TR was deemed clinically insignificant, a result of collateral damage from other underlying conditions, often left-sided valvular lesions, pulmonary hypertension, or atrial fibrillation. This school of thought has influenced the management of secondary TR for a long time, which was largely conservative with diuretic therapy or with TR expected to improve following treatment of the culprit conditions. Surgical intervention for TR was at best scarce, even for severe TR. If tricuspid valve surgeries were performed, they were often carried out during concomitant left-sided valve surgery or when other indications for open heart surgery were present. In the USA, an estimated 1.5 million of the adult population were affected by moderate to severe TR. However, according to data from the Society of Thoracic Surgeon (STS), 5000 isolated tricuspid valve surgeries were performed each year in the USA, reflecting the vast unmet clinical needs in the management of TR. As our understanding of the natural history of TR has improved in recent years, the tricuspid valve has finally been receiving the attention that it deserves. Indeed, as the surgical techniques improve and the momentum of percutaneous tricuspid intervention gathers, the tricuspid valve has been garnering increasing interest from interventionists, cardiac imagers, heart failure specialists, and cardiac surgeons alike. Despite the attention from the cardiac community, long-term outcome studies on TR are still scarce. In addition, the prognostication of patients with TR is often muddled by the heterogeneity of TR aetiologies or confounded by the presence of left-sided valve diseases, most notably mitral regurgitation or stenosis. These gaps in the literature form the major impetus for the study by Topilsky et al. in the current issue of the European Heart Journal, where the authors studied the specific risk attached to TR in the presence of left ventricular (LV) systolic dysfunction. In order to separate the wheat from the chaff, the authors selected only patients with secondary TR and reduced LV ejection fraction (EF <50%). Importantly, the study patients had no other significant valvular heart disease, defined as organic valve lesions of moderate or higher severity, neither did they have organic or primary TR, congenital causes of TR, or any previous valve surgery. The stringent selection criteria positioned the authors’ work well at isolating the impact of secondary TR on long-term outcome. The authors studied a fair number, albeit a historical cohort, of consecutive patients enrolled in the Mayo Clinic prospective TR registry from 1995 to 2005. Clinical outcomes up to 5 years, which included all-cause death, new onset of atrial fibrillation (AF), or heart failure admission, were reported. Quantitative assessment of TR using the proximal isovelocity surface area (PISA) method to calculate effective regurgitant orifice area (EROA) was performed for all patients. Severe TR was defined as an EROA >_0.4 cm. Right ventricular function was evaluated qualitatively and by indexes of myocardial performance (right ventricular index of myocardial performance or myocardial performance index). Based on the EROAs, the study population was divided into cases, denoted by patients with mild to severe TR and controls, which included patients with trivial TR. Clinical presentation and outcomes were compared between the case and control groups. To correct for potential confounders, the authors matched the groups by age, gender, EF, year of diagnosis, co-morbidity index, and TR peak velocity. At least mild–moderate to severe isolated TR was independently associated with excess mortality and cardiac events, warranting heightened attention to TR grading (Take home figure). Patients with mild–moderate TR had higher NYHA class, signs of right heart failure, liver dysfunction, and right ventricular enlargement on

The Right Heart-Pulmonary Circulation Unit and Left Heart Valve Disease

Valvular heart disease (VHD) is frequently accompanied by pulmonary hypertension (PH). In asymptomatic patients, PH is rare, although the exact prevalence is unknown and mainly stems from the severity of the VHD and the presence of diastolic dysfunction. PH can also be depicted during exercise echocardiography. PH either at rest or during exercise is also a powerful determinant of outcome and is independently associated with reduced survival, regardless of the severity of the underlying valvular pathology. Therefore, because PH is a marker of poor prognosis, assessment of PH in VHD is crucial for risk stratification and management of patients with VHD.

Transthoracic Ultrasound Imaging of the Descending Thoracic Aorta: Could We, Should We, and Would We?

As we enter the era of multimodality imaging, we are presented with a barrage of imaging modalities, which at times offer comparable or even overlapping clinical solutions. Technological advancements have also brought new life to established imaging modalities such as ultrasound. Recent studies have shown that 4D contrast enhanced ultrasound could possibly assess fenestrated endovascular aneurysm in the future, while 3D ultrasound has been shown to accurately diagnose endoleaks and assess abdominal aortic aneurysm diameter. Whether we can capitalise on the various imaging modalities depends on a good understanding of the pros and cons of each modality, as well as sound clinical judgement. Ultrasound retains its appeal in the era of multimodality imaging because of its relatively low cost, easy availability, and safety. However, when it comes to diagnosing thoracic aortic pathology, its widespread use has been hampered by limitations such as poor far field resolution and difficult imaging windows because of patient’s body habitus, presence of lung tissue, or ribs. Consequently, imaging modalities such as computed tomographic angiography and magnetic resonance angiography, which offer multiplanar reconstruction, comprehensive coverage, superior image quality and ability to depict fine details, such as thrombus formation, aortic dissection entry site, or endoleaks, are becoming increasingly commonplace in routine clinical practice. Published guidelines on multimodality imaging of the thoracic aorta, for example the European Association of Cardiovascular Imaging/American Society of Echocardiography Guidelines published in 2015 and the latest Clinical Practice Guidelines by the European Society of Vascular Surgery (ESVS) published in 2017, provided similar recommendations on the topic of thoracic aortic imaging. Both guidelines acknowledge the use of transthoracic echocardiography (TTE) as a useful tool for evaluating the aortic root, ascending aorta, and aortic arch in patients with good acoustic windows. However, TTE is deemed less useful for evaluating the descending aorta as TTE cannot reliably evaluate the entire thoracic aorta in patients with suspected aortic disease. Currently, multidetector computed tomographic (CT) angiography is the first line diagnostic modality for descending aorta pathology (Class I, Level of evidence C), while transoesophageal echocardiography (TOE) is considered the second line imaging modality when CT is unavailable, contraindicated, or inconclusive (Class IIa, Level of evidence C). In the work by D’abate et al., the authors examined the feasibility of transthoracic ultrasound for imaging the descending thoracic aorta using a dedicated protocol. The study

Age and ejection fraction modify the impact of atrial fibrillation on acute heart failure outcomes

Atrial fibrillation (AF) and heart failure (HF) often coexist, share common predisposing factors and perpetuate one another.1 It has been suggested that the association of AF with HF may be modified by other clinical factors such as age, sex, left ventricular ejection fraction (LVEF), diabetes, or prior myocardial infarction (MI).2,3 However, this has not been systematically assessed in a large unselected population of HF patients across the entire LVEF spectrum. The aim of our study was to identify clinical factors that modify the effects of AF and assess the impact on a composite outcome of all-cause mortality or HF readmission in a cohort of HF patients with a view towards improving risk stratification of AF patients. We studied consecutive patients admitted for acute decompensated HF in the National Cardiac Centre and the largest tertiary hospital in Singapore from 1 January 2008 to 31 December 2013. The diagnosis of acute HF was based on the 10th version of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) code on discharge. Patients were enrolled and followed up as part of the nationwide Singapore Cardiac Data Bank.3 We focused our investigation on index HF admissions. The presence of AF was determined by either a documented history of AF/atrial flutter on admission or electrocardiogram showing AF/atrial flutter. We used the guideline definitions of LVEF ≥50% as HF with preserved LVEF (HFpEF), LVEF 40–49% as HF with midrange LVEF (HFmrEF), and LVEF <40% as HF with reduced LVEF (HFrEF). Mortality data were obtained from the National Registry of Diseases Office (NRDO). The study endpoint was all-cause mortality or HF admission up to 31 December 2014. Cox regression analysis was used to test for interaction effects of AF status (AF vs. no AF) with age, sex, LVEF, diabetes, and prior MI relative to study outcome after adjusting for sex, hypertension, diabetes, prior HF, chronic obstructive pulmonary disease/asthma, systolic blood pressure, serum sodium, serum creatinine, and haemoglobin. Age and LVEF were identified as statistically significant effect modifiers of AF on all-cause mortality or HF readmission, resulting in five subgroup analyses: age subgroups of <60 and ≥60 years, and LVEF subgroups of HFpEF, HFmrEF, and HFrEF. Hazard ratios (HRs) for AF vs. no AF were estimated in each of the five subgroup analyses. HRs were adjusted for sex, hypertension, diabetes, prior myocardial infarction, prior HF, chronic obstructive pulmonary disease/asthma, systolic blood pressure, serum sodium, serum creatinine, haemoglobin, LVEF (in age subgroups), and age (in LVEF subgroups). In addition, Kaplan–Meier survival curves were obtained for each of the five subgroups and compared using the log-rank test. Of a total of 6304 patients with HF (mean age 69±13 years; 54% men; 46% with HFrEF, 12% with HFmrEF, 42% with HFpEF; 49.6% diabetic; 25.9% with history of MI), 31% (n= 1942) had AF. Across LVEF groups, patients with AF were older and more likely to have a history of stroke but less likely to have diabetes or prior MI compared with patients without AF. Over a mean followup of 1.9 years, there were 4010 outcome events (1589 all-cause mortality, 2421 HF readmission). After adjustment for confounders, AF was found to be an independent risk factor for all-cause mortality or HF readmission [adjusted HR 1.15, 95% confidence interval (CI) 1.07–1.23, P< 0.001]. Interaction effects of AF with age (P= 0.015) and LVEF (P= 0.020) on all-cause mortality or HF readmission were statistically significant, whereas the effects of sex, diabetes, and prior MI were not. Risk of all-cause mortality or HF readmission due to AF was significantly higher in patients aged ≥60 years (HR 1.19, 95% CI 1.11–1.28, P< 0.001) (Figure 1B) and those with HFpEF (HR 1.22, 95% CI 1.09–1.35, P< 0.001) (Figure 1C) compared with patients with no AF, but not in patients aged <60 years (Figure 1A), or those with HFmrEF or HFrEF (Figure 1D and E). Our study indicates that AF is an independent predictor of increased risk of all-cause mortality or HF readmission in HF patients and extends prior knowledge by highlighting the modifying effects of age and LVEF on the association of AF with HF outcome. We identified specific subgroups of patients, those ≥60 years of age and patients with HFpEF for whom AF was independently associated with higher risk of all-cause mortality or HF readmission. Our findings concur with those of Eapen et al. who showed that LVEF interacts with a patient’s rhythm.2 In that study, AF was associated with increased 30-day mortality compared with sinus rhythm in patients with HFpEF. In patients with HFrEF, rhythm state did not make a difference in 30-day mortality. Furthermore, there was no interaction between LVEF and rhythm state on readmission rate. However, the follow-up period was only 30 days in that study compared with a median of 1.9 years in our study. A recent report from the GREAT Registry showed that, compared with other precipitating factors, AF as a precipitant of acute HF was associated with reduced risk of 90-day all-cause mortality. A possible explanation for the difference in findings with the present study could be that, in the present study, the AF group includes all patients with documented AF at admission, regardless of whether AF was considered responsible for the acute decompensation or not.4 This study has a few limitations. Our data were prospectively captured, but retrospectively analysed. We did not have information regarding the type of AF, i.e. permanent, persistent, or paroxysmal, or development of new AF during follow-up. Strengths of our study include the relatively large number of patients and the robust mortality data. Singapore has adopted an island-wide electronic medical system that makes it possible to obtain high quality health records and mortality data using the public health informatics infrastructure. In conclusion, age and LVEF modify AF prognosis in patients hospitalized for HF. The risk of all-cause mortality or HF readmission is increased in older patients and those with HFpEF in the presence of AF. Whether more aggressive treatment strategies would improve outcomes in these higher-risk patients warrants further investigation. Conflict of interest: C.S.P.L reports grants from National Medical Research Council of Singapore, non-financial support from Boston Scientific, non-financial support from Bayer, non-financial support from Thermofisher, non-financial support from Medtronic, nonfinancial support from Vifor Pharma, Bayer, Novartis, Takeda, Merck, Astra Zeneca, Janssen Research & Development, LLC, Menarini, Boehringer Ingelheim, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, Roche, Amgen, outside the submitted work. C.S.P.L. has a patent PCT/SG2016/050217 pending. All other authors have no conflicts of interest to declare.

Management of Asymptomatic Severe Degenerative Mitral Regurgitation

ABSTRACT The decision for surgery in the management of asymptomatic severe degenerative mitral regurgitation (MR) is about doing the right thing at the right time and place. European and American guidelines have provided us with guidance on surgical indications, albeit with different levels of recommendations. However, the timing for surgery especially in asymptomatic patients not meeting Class I indications for intervention, i.e. no evidence of left ventricular dysfunction is still avidly debated. In this review, we will present the literature on the indications and timing of surgical intervention in asymptomatic severe MR, covering guidelines from both societies. We will also touch on the emerging role of other imaging techniques, biomarkers and exercise stress testing. Finally, we will present arguments for and against both management strategies, i.e. early surgery and watchful waiting. To summarize, the management of patients with asymptomatic severe degenerative MR should be a joint decision between all members of the Heart Team and tailored according to the availability of surgical expertise, patient’s surgical risk and patient’s wishes.

Exercise Testing in Mitral Regurgitation

Mitral regurgitation (MR) is the second most common valvular heart disease referred for corrective surgery. Diagnostic and management dilemmas are not uncommon when dealing with MR patients. Exercise testing plays an important role in sorting out some of these clinical challenges. In primary asymptomatic MR, exercise testing allows symptom assessment, confident link of symptoms to valve disease severity, safe deferral of surgery for the next 1-year in patients with preserved exercise capacity, insights into the mechanism of exercise-induced dyspnea and helps in individual risk stratification. Moreover, exercise testing in the form of exercise stress echocardiography is also useful in the evaluation of patients with secondary ischemic MR for risk stratification as well as for the detection of patients with moderate ischemic MR in whom mitral valve repair at the time of surgical revascularization may add benefit.

Exercise Doppler echocardiography for the diagnosis of pulmonary hypertension: renewed interest and evolving roles

Exercise-induced pulmonary hypertension (PHT) was defined historically as an increase of >30 mmHg in the mean pulmonary artery pressure (MPAP) during exercise in patients who otherwise had a normal MPAP at rest (1). This concept was adopted for almost two decades before it was dropped from the diagnostic criteria of PHT in 2008 following the 4th World Symposium on PHT due to the ambiguity in the ncut-off values for abnormality (2). In recent years, however, the tide might have turned. New and improved definitions for exercise PHT have been proposed and validated in a variety of patient cohorts, generating interest and bringing exercise PHT back into the limelight (3,4). As the latest iteration of the World Symposium on PHT in Nice approaches, this paper by van Riel et al. is both timely and relevant.

What Does 3D Echocardiography Add to 2D Echocardiography in the Assessment of Mitral Regurgitation

Purpose of ReviewThe purpose of this review was to elucidate the additional value of 3D echocardiography for the assessment of mitral regurgitation (MR) compared to standard 2D echocardiography.Recent Findings3D echocardiography provides key information, aetiology, degenerative mitral valve disease vs. secondary MR, causes and mechanism, severity by measurements of effective regurgitant orifice area and regurgitant volume; likelihood of reparability and assessment of pre- and intra-mitral valve transcatheter procedures.Summary3D echocardiography as a promising method for assessment of MR is useful and crucial for research, clinical practice and patient management in all heart valve team members.