Subclinical Myocardial Fibrosis in Systemic Lupus Erythematosus as Assessed by Pulse-Cancellation Echocardiography: A Pilot Study.

The aim of this study was to examine whether scar imaging echocardiography with ultrasound multi-pulse scheme (eSCAR) can detect subclinical myocardial involvement in systemic lupus erythematosus (SLE). We consecutively recruited SLE patients and controls matched for age, sex, and cardiovascular risk factors. Participants with cardiac symptoms or a prior history of heart disease were excluded. All participants underwent eSCAR and speckle tracking echocardiography (STE) with global longitudinal strain (GLS) assessment. SLE patients were assessed for disease activity and were followed up for 12 months. Myocardial scars by eSCAR were observed in 19% of SLE patients, almost exclusively localized at the inferoseptal myocardial segments, and in none of the controls. GLS was significantly lower in most myocardial segments of SLE patients compared with the controls, especially in the inferoseptal segments. eSCAR-positive SLE patients received a higher cumulative and current dose of prednisone, and had significantly higher levels of anti-dsDNA antibodies (p = 0.037). eSCAR-positive patients were at higher risk of having SLE flares over follow-up (hazard ratio: 4.91; 95% CI 1.43-16.83; p = 0.0001). We identified inferoseptal myocardial scars by eSCAR in about one-fifth of SLE patients. Subclinical myocardial involvement was associated with glucocorticoid use and anti-dsDNA antibodies.

Novel Approaches in Cardiac Imaging for Non-invasive Assessment of Left Heart Myocardial Fibrosis.

In the past, the identification of myocardial fibrosis was only possible through invasive histologic assessment. Although endomyocardial biopsy remains the gold standard, recent advances in cardiac imaging techniques have enabled non-invasive tissue characterization of the myocardium, which has also provided valuable insights into specific disease processes. The diagnostic accuracy, incremental yield and prognostic value of speckle tracking echocardiography, late gadolinium enhancement and parametric mapping modules by cardiac magnetic resonance and cardiac computed tomography have been validated against tissue samples and tested in broad patient populations, overall providing relevant clinical information to the cardiologist. This review describes the patterns of left ventricular and left atrial fibrosis, and their characterization by advanced echocardiography, cardiac magnetic resonance and cardiac computed tomography, allowing for clinical applications in sudden cardiac death and management of atrial fibrillation.

Hyperventilation-induced heart rate response as a potential marker for cardiovascular disease.

An increase of heart rate to physical or mental stress reflects the ability of the autonomous nervous system and the heart to respond adequately. Hyperventilation is a user-controlled breathing maneuver that has a significant impact on coronary function and hemodynamics. Thus, we aimed to investigate if the heart rate response to hyperventilation (HRRHV) can provide clinically useful information. A pooled analysis of the HRRHV after 60 s of hyperventilation was conducted in 282 participants including healthy controls; patients with heart failure (HF); coronary artery disease (CAD); a combination of both; or patients suspected of CAD but with a normal angiogram. Hyperventilation significantly increased heart rate in all groups, although healthy controls aged 55 years and older (15 ± 9 bpm) had a larger HRRHV than each of the disease groups (HF: 6 ± 6, CAD: 8 ± 8, CAD+/HF+: 6 ± 4, and CAD-/HF-: 8 ± 6 bpm, p < 0.001). No significant differences were found between disease groups. The HRRHV may serve as an easily measurable additional marker of cardiovascular health. Future studies should test its diagnostic potential as a simple, inexpensive pre-screening test to improve patient selection for other diagnostic exams.

Comparison of the biodegradable polymer everolimus-eluting stent with contemporary drug-eluting stents: A systematic review and meta-analysis.

AIMS: Despite similar efficacy and safety profile in pilot studies, bioresorbable polymer drug-eluting stents (BP-DES) could have potential benefit over latest generation durable polymer (DP)-DES by facilitating vessel healing, therefore reducing inflammation and neoatherosclerosis leading to enhanced clinical safety. Therefore, we sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of everolimus-eluting BP-DES (BP-EES) to second-generation DP-DES. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to examine the safety and efficacy of BP-EES in patients treated for coronary artery disease. We searched PubMed, Scopus, and the Cochrane Library through February 2018 for RCTs that included outcome data on BP-EES. We identified four eligible studies, which included a total of 4631 patients. Three studies reported a follow-up of one year and one study of five years. The BP-EES group, included 2315 patients and the DP-DES group included 2316 patients (1143 treated with DP-EES and 1173 treated with zotarolimus eluting DP-DES). Patient's characteristics were comparable between the two groups except for higher prevalence of prior MI in the DP-DES group (25.7 vs 22.5%, respectively, p = 0.001). Procedural characteristics were comparable among groups except for slightly longer lesions in the BP-EES group compared to the DP-DES group (mean 15.1 vs 14.9 mm, p = 0.04). No significant differences were observed for cardiac mortality (p = 0.72), occurrence of MI (p = 0.64), any TLR (p = 0.93), ST (p = 0.85) or major adverse cardiac events (p = 0.43). CONCLUSION: Overall, based on the available data BP-EES had similar one-year outcomes to contemporary DP-DES. Whether these devices could enhance clinical safety remains to be evaluated at longer follow-up.

Usefulness of Left Atrial Remodeling in Predicting CardiacToxicity During Trastuzumab Therapy for Breast Cancer.

Trastuzumab is a key therapy for patients with human epidermal growth factor receptor 2 positive breast cancer (BC). However, it may cause left ventricular dysfunction, resulting in withdrawal of therapy. Left atrium (LA) enlargement has proven to cue subclinical ventricular dysfunction in various clinical setting. Aim of the study was to investigate the association between LA volume index (LAVI) change over time and the development of Cancer Therapeutics Related Cardiac Dysfunction (CTRCD). Consecutive human epidermal growth factor receptor 2 positive BC patients were retrospectively included. Transthoracic echocardiography was performed before starting Trastuzumab and at every 3 up to 12 months. LA volume was measured using the modified Simpson's rule and indexed for body surface area. Ninety patients formed the study population. All patients had a complete 12 months follow-up. Mean baseline LAVI was 27 ± 8 ml/m2 and it was dilated (≥34 ml/m2) in 10 patients (11%). During follow-up, CTRCD occurred in 19 (21%) patients and there was modest LAVI enlargement, with a mean increase of 3 ± 2 ml/m2 (p = 0.0002 vs. baseline). LAVI dilation was significantly higher in patients with CTRCD (average increase at the time of CTRCD vs. baseline: 7 ± 6 ml/m2, p = 0.008), versus patients without CTRCD (average increase at 12 months of follow-up 2±1, p = 0.02), p for comparison = 0.004. LAVI dilatation over time predicted CTRCD independently from baseline LAVI values and the presence of systemic arterial hypertension (OR for 5 ml/m2 dilation was 1.56 [95%CI 1.09 to 2.37], p = 0.01). Trastuzumab related CTRCD is associated with significant LAVI morphological remodeling in BC patients.

Left atrial volume in patients with HER2-positive breast cancer: One step further to predict trastuzumab-related cardiotoxicity.

BACKGROUND: Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities. HYPOTHESIS: Baseline LA volume enlargement might predict TZ-related LV dysfunction. METHODS: HER2-positive breast cancer patients receiving TZ and undergoing transthoracic echocardiography at baseline and at follow-up every 3 months were retrospectively recruited. One-hundred sixty-two patients formed the study population. RESULTS: Baseline LAVI was dilated in 14 patients (8.6%). Mean follow-up was 14 ± 4 months. Cardiotoxicity occurred in 24 patients (14.8%). LAVI was an independent predictor of TZ-induced LV dysfunction in a clinical model, after adjustment for age and hypertension (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.03-1.82, P = 0.03); and in a hemodynamic model, including ventricular sizes and systolic blood pressure level (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.01-1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased progressively, in parallel with LAVI values. CONCLUSIONS: Baseline LA dilatation emerges as a condition associated with the development of cardiotoxicity in HER2-positive breast cancer patients treated with TZ.

Caseous calcification of the mitral annulus: a rare entity confirmed by cardiovascular magnetic resonance imaging.

Caseous calcification of the mitral annulus (CCMA) is a rare variant of mitral annulus calcification which presents as a semilunar echodense mass with smooth borders and central areas of echolucency. It is an under-recognized benign entity and can be misdiagnosed for a number of pathologies including tumors, abscesses and thrombi. We present a representative CCMA case and highlight its typical appearance on magnetic resonance imaging.

Drug eluting balloon for the treatment of patients with coronary artery disease: Current perspectives.

Despite the improvement of outcomes after the introduction of bare metal and drug eluting stents for the treatment of CAD, certain type of patients have still an increased risk of stent failure. An alternative is represented by drug-eluting balloons (DEB). This innovation could give potential benefits in particular for the in-stent restenosis (ISR) and the de-novo lesions. In the first setting DEB have shown results superior to those with plain-balloon angioplasty and similar to those with first generation DES. Their performance seems to be more evident in BMS-ISR than in DES-ISR, showing a reliable effectiveness in those cases of recalcitrant ISR or when dual antiplatelet therapy is not indicated. In the context of de-novo lesions the use of DEB as unique strategy results more safe and feasible than a strategy with combined BMS implantation. The results are comparable to DES in lesions limited to small coronary vessels. Other particular scenarios, like bifurcations, acute myocardial infarction and diffuse disease, have been approached with DEB resulting in very heterogeneous outcomes. At present, given the high efficacy of last generation DESs, DEBs should be considered where clinical and angiographic conditions require the avoidance of stent implantation.

Optimizing the role of transthoracic echocardiography to improve the cardiovascular risk stratification: the dream of subclinical coronary artery disease detection.

Detecting coronary artery disease at a subclinical level has always been a challenging task for cardiologists. Various non-invasive echocardiographic approaches such as measurements of left ventricular hypertrophy, diastolic function, left atrial enlargement, valve sclerosis and calcification, epicardial fat thickness, and pulse wave velocity have been proposed to integrate the available risk-charts. The present review is a collection of evidence that supports the role of the above mentioned features in cardiac risk stratification, summarizing the state of the art in non-invasive echocardiographic coronary risk assessment. Each parameter is presented with its strengths and weaknesses, aiming to trace the future directions for the development of a reliable non-invasive approach.

A New Method to Evaluate Atrial Hemodynamic and Quantify Mitral Regurgitation using Cardiovascular Magnetic Resonance: The Pulmonary Venous Flow Approach.

Pulmonary venous flow (PVF) provides incremental information on left ventricular (LV) diastolic function, and can support the diagnosis of severe mitral regurgitation (MR). The suggestion has been made to combine the left atrial filling volume (LA Fill) and PVF for estimating the mitral regurgitant volume, but echocardiographic PVF evaluation is known to have many limitations. The present case report includes an example of how to assess PVF using cardiovascular magnetic resonance, and a new method is proposed for quantification of the mitral regurgitant volume.

Left ventricular end-diastolic volume as early indicator of trastuzumab-related cardiotoxicity in HER2+ breast cancer patients: results from a single-center retrospective study.

BACKGROUND: Adjuvant trastuzumab therapy increases survival rates in patients with early HER2-positive breast cancer, although it can be potentially cardiotoxic. The aim of this study was to evaluate the prevalence of left ventricular (LV) systolic dysfunction; and the relationship between the presence of cardiovascular risk factors, cardiac therapy and/or echocardiographic parameters of systolic function at baseline and the development of cardiotoxicity in such patients. METHODS: A total of 227 patients were retrospectively reviewed. Cardiotoxicity was defined as a decrease in LV ejection fraction (EF) below 50% or an absolute decrease of >10 points below the baseline value or any indication of heart failure. Each patient underwent echocardiography at baseline and at follow-up every three months. RESULTS: The prevalence of cardiotoxicity was 17.6% (15.4% asymptomatic, 2.2% symptomatic). Patients developing LV dysfunction presented hypertension (P=0.041) and diabetes (P=0.01) and used cardiac therapy at baseline more frequently. Smoke habit, age >50 and use of angiotensin-converting enzyme (ACE)-inhibitors, were independent predictors of cardiac damage. Furthermore, patients with LV dysfunction showed baseline LV end-diastolic volume (EDV) higher than those who did not and baseline EDV (OR=1.02; 95% CI: 1.00-1.04; P=0.027) independently predicted cardiotoxicity with 58 mL/m2 as best cut-off point (AUC=0.65, 95% CI: 0.55-0.75]). CONCLUSIONS: The prevalence of trastuzumab-related cardiotoxicity in patients with HER2-positive early breast cancer is relatively frequent, although asymptomatic in most cases. Baseline EDV resulted as independent predictor of cardiotoxicity suggesting that EDV may be more reliable than LVEF to identify patients at higher risk of developing cardiac damage.

Prognosis and disease progression in patients under 50 years old undergoing PCI: the CRAGS (Coronary aRtery diseAse in younG adultS) study.

OBJECTIVE: Young patients undergoing percutaneous coronary intervention (PCI) are generally considered at low procedural risk, but the potentially aggressive nature of coronary artery disease and long expectancy of life expose them to a high risk of recurrent coronary events. The extent and determinants of disease progression in this patient subset remain largely unknown. The aim of the present study was to evaluate general risk factors for late outcomes among patients ≤50 years old who underwent PCI. METHODS: Coronary aRtery diseAse in younG adults (CRAGS) is a multicenter European retrospective registry that enrolled 1617 patients (age ≤50 years) who underwent PCI over the years 2002-2012. The median follow-up was 3.0 years. RESULTS: The majority of patients were smokers who were nevertheless prescribed adequate secondary prevention medication, including statins, aspirin, beta blockers and/or ACE inhibitors/AT blockers. At 5 years, survival was 97.8%, while freedom from major adverse cardiac and cerebrovascular events was 74.1%, from repeat revascularization 77.8% and from myocardial infarction 89.9%. Altogether 13.5% of patients exhibited disease progression that indicated a need for repeat revascularization. Other indications for repeat revascularization were restenosis (7.1%) and stent thrombosis (2.1%) at the 5-year follow-up. Independent post-PCI predictors of disease progression were multivessel disease, diabetes and hypertension. CONCLUSION: PCI is associated with excellent survival in patients ≤50 years old. Nevertheless, despite guideline-adherent medication, every eighth patient underwent repeat revascularization due to disease progression diagnosed at the median follow-up of three years, underscoring the need for more effective secondary prevention than currently available.

Comparison of 30-day and 5-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients aged≤50 years (the Coronary aRtery diseAse in younG adultS Study).

Data on the outcome of young patients after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are scarce. Data on 2,209 consecutive patients aged≤50 years who underwent CABG or PCI were retrospectively collected from 15 European institutions. PCI and CABG had similar 30-day mortality rates (0.8% vs 1.4%, p=0.27), late survival (at 5 years, 97.8% vs 94.9%, p=0.082), and freedom from stroke (at 5 years, 98.0% and 98.0%, p=0.731). PCI was associated with significantly lower freedom from major adverse cardiac and cerebrovascular events (at 5 years, 73.9% vs 85.0%, p<0.0001), repeat revascularization (at 5 years, 77.6% vs 92.5%, p<0.0001), and myocardial infarction (at 5 years, 89.9% vs 96.6%, p<0.0001) compared with CABG. These findings were confirmed in propensity score-adjusted and matched analyses. Freedom from major adverse cardiac and cerebrovascular events after PCI was particularly low in diabetics (at 5 years, 58.0% vs 75.9%, p<0.0001) and in patients with multivessel disease (at 5 years, 63.6% vs 85.1%, p<0.0001). PCI in patients with ST elevation myocardial infarction was associated with significantly better 5-year survival (97.5% vs 88.8%, p=0.001), which was driven by its lower 30-day mortality rate (1.5% vs 6.0%, p=0.017). In conclusion, patients aged≤50 years have an excellent immediate outcome after either PCI or CABG with similar long-term survival when used according to the current clinical practice. PCI was associated with significantly lower freedom from myocardial infarction and repeat revascularization.

Basic data from 176 studies on the immediate outcome after aortic valve replacement with or without coronary artery bypass surgery.

OBJECTIVE: The aim of this study was to summarize the immediate outcome after aortic valve replacement (AVR) with or without coronary artery bypass grafting (CABG). DESIGN: Systematic review and meta-analysis. SETTING: University hospitals. PARTICIPANTS: Participants were 683,286 patients who underwent AVR with or without CABG. Patients undergoing other major cardiac procedures were excluded from this analysis. INTERVENTIONS: AVR with or without CABG. MEASUREMENTS AND MAIN RESULTS: Operative mortality after AVR with or without concomitant CABG was 4.3%, stroke 2.1%, pacemaker implantation 5.9%, and dialysis 2.2%. After isolated AVR, operative mortality was 3.3%, stroke 1.7%, pacemaker implantation 3.3%, and dialysis 1.6%. Mortality was increased among very elderly (< 60 years: 3.3%, 60-69 years: 2.7%, 70-79 years: 3.8%,≥ 80 years: 6.1%, p < 0.001). Prevalence of minimally invasive AVR (mini-AVR) was associated with significantly lower operative mortality (p = 0.039, 46 studies). Mini-AVR only tended toward lower mortality when included in meta-regression analysis as a dichotomous variable (mini-AVR 4,367 patients: 2.3%, 95% CI 1.8-2.9% v full sternotomy 11,076 patients: 3.5%, 95% CI 28-4.1%, p = 0.088). Operative mortality after AVR plus CABG was 5.5% (versus isolated AVR: p < 0.001), stroke 3.0%, pacemaker implantation 3.9%, and dialysis 5.6%. Mortality was high in all age strata, particularly among very elderly (mean age < 70 years: 4.8%, mean age 70-79 years: 4.7%; mean age ≥ 80 years: 8.4%, p = 0.002). CONCLUSIONS: Isolated AVR is associated with low mortality and morbidity. Coronary artery disease requiring concomitant CABG increases the operative mortality. Patients requiring AVR and CABG should be the main target of less-invasive treatment strategies.

Pooled estimates of immediate and late outcome of mitral valve surgery in octogenarians: a meta-analysis and meta-regression.

OBJECTIVE: The authors evaluated the outcome of patients≥80 years undergoing mitral valve (MV) surgery. DESIGN: Systematic review of the literature and meta-analysis. SETTING: None. PARTICIPANTS: None. INTERVENTIONS: None. MAIN RESULTS: Twenty-four studies reporting on 5,572 patients ≥80 years of age who underwent MV surgery were included in this analysis. Pooled proportion of operative mortality was 15.0% (95% confidence interval [CI] 11.9-18.1), stroke was 3.9% (95% CI 2.6-5.2), and dialysis was 2.7% (95% CI 0.5-4.9). Early date of study (p = 0.014), increased age (p = 0.006), MV replacement (p = 0.008), procedure other than isolated MV surgery (p = 0.010), MV surgery associated with coronary artery surgery (p = 0.029), aortic cross-clamping time (p<0.001), and cardiopulmonary bypass time (p<0.001) were associated significantly with increased operative mortality. MV repair had lower operative mortality compared with MV replacement (7.3% v 14.2%, relative risk 0.573, 95% CI 0.342-0.962). Random-effects metaregression showed that prolonged aortic cross-clamping time (p = 0.005) was the only determinant of increased operative mortality, even when adjusted (p<0.001) for date of study (p = 0.004). Operative mortality was significantly higher in studies reporting a mean cross-clamp time >90 minutes (17.0% v 7.4%, p<0.001). Survival rates at 1, 3, and 5 years were 76.1%, 67.7%, and 56.5%, respectively. CONCLUSIONS: MV surgery in patients ≥80 years of age is associated with operative mortality, which has decreased significantly during recent years. Prolonged aortic cross-clamp time is a major determinant of operative mortality. MV repair may achieve better results than MV replacement in the very elderly. Five-year survival of these patients is good and justifies surgical treatment of MV diseases in octogenarians.