Diagnostic Challenges in Aortic Stenosis.

Aortic stenosis (AS) is the most prevalent degenerative valvular disease in western countries. Transthoracic echocardiography (TTE) is considered, nowadays, to be the main imaging technique for the work-up of AS due to high availability, safety, low cost, and excellent capacity to evaluate aortic valve (AV) morphology and function. Despite the diagnosis of AS being considered straightforward for a very long time, based on high gradients and reduced aortic valve area (AVA), many patients with AS represent a real dilemma for cardiologist. On the one hand, the acoustic window may be inadequate and the TTE limited in some cases. On the other hand, a growing body of evidence shows that patients with low gradients (due to systolic dysfunction, concentric hypertrophy or coexistence of another valve disease such as mitral stenosis or regurgitation) may develop severe AS (low-flow low-gradient severe AS) with a similar or even worse prognosis. The use of complementary imaging techniques such as transesophageal echocardiography (TEE), multidetector computed tomography (MDTC), or cardiac magnetic resonance (CMR) plays a key role in such scenarios. The aim of this review is to summarize the diagnostic challenges associated with patients with AS and the advantages of a comprehensive multimodality cardiac imaging (MCI) approach to reach a precise grading of the disease, a crucial factor to warrant an adequate management of patients.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

Incidence, predictors and prognostic impact of intracranial bleeding within the first year after an acute coronary syndrome in patients treated with percutaneous coronary intervention.

BACKGROUND: The rate of intracranial haemorrhage after an acute coronary syndrome has been studied in detail in the era of thrombolysis; however, in the contemporary era of percutaneous coronary intervention, most of the data have been derived from clinical trials. With this background, we aim to analyse the incidence, timing, predictors and prognostic impact of post-discharge intracranial haemorrhage in patients with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS: We analysed data from the BleeMACS registry (patients discharged for acute coronary syndrome and undergoing percutaneous coronary intervention from Europe, Asia and America, 2003-2014). Analyses were conducted using a competing risk framework. Uni and multivariate predictors of intracranial haemorrhage were assessed using the Fine-Gray proportional hazards regression analysis. The endpoint was 1-year post-discharge intracranial haemorrhage. RESULTS: Of 11,136 patients, 30 presented with intracranial haemorrhage during the first year (0.27%). The median time to intracranial haemorrhage was 150 days (interquartile range 55.7-319.5). The fatality rate of intracranial haemorrhage was very high (30%). After multivariate analysis, only age (subhazard ratio 1.05, 95% confidence interval 1.01-1.07) and prior stroke/transient ischaemic attack (hazard ratio 3.29, 95% confidence interval 1.36-8.00) were independently associated with a higher risk of intracranial haemorrhage. Hypertension showed a trend to associate with higher intracranial haemorrhage rate. The combination of older age (⩾75 years), prior stroke/transient ischaemic attack, and/or hypertension allowed us to identify most of the patients with intracranial haemorrhage (86.7%). The annual rate of intracranial haemorrhage was 0.1% in patients with no risk factors, 0.2% in those with one factor, 0.6% in those with two factors and 1.3% in those with three factors. CONCLUSION: The incidence of intracranial haemorrhage in the first year after an acute coronary syndrome treated with percutaneous coronary intervention is low. Advanced age, previous stroke/transient ischaemic attack, and hypertension are the main predictors of increased intracranial haemorrhage risk.

Risk of cancer after an acute coronary syndrome according to the type of P2Y12 inhibitor.

INTRODUCTION: There are conflicting clinical and laboratory data about the effect of dual antiplatelet therapy (DAPT) on cancer incidence, including analysis suggesting an increased cancer risk. This study aims to analyze if there are differences in the incidence of cancer according to the type of P2Y12 inhibitor prescribed (clopidogrel, prasugrel, or ticagrelor), among a population of acute coronary syndrome (ACS) survivors treated with DAPT. MATERIAL AND METHODS: A retrospective study was conducted among 4229 consecutive ACS patients discharged from a tertiary hospital with DAPT from 2010 to 2016. Cox regression, propensity score, and survival-time inverse probability analysis were done. RESULTS: A total of 311 were diagnosed of cancer during a median follow-up of 46.2 months. The cumulative incidence function (CIF) of cancer (per 100 patients/year) was 2.2 for clopidogrel, 1.6 for prasugrel, and 0.3 for ticagrelor. After multivariate analysis, we have found that ticagrelor resulted associated with lower cancer risk than clopidogrel (sHR 0.20: 95% CI 0.05-0.84; p = 0.028), without differences between prasugrel and clopidogrel. After propensity score matching, ticagrelor was also associated with lower incidence of cancer than clopidogrel/prasugrel (sHR 0.22; 95% CI 0.05-0.90; p = 0.036), regardless of DAPT duration. CONCLUSION: DAPT with ticagrelor could be associated with lower follow-up cancer incidence than DAPT with clopidogrel or prasugrel after an ACS.

Renin-Angiotensin System Blockade and Risk of Heart Failure After Myocardial Infarction Based on Left Ventricular Ejection Fraction: A Retrospective Cohort Study.

INTRODUCTION: The goal of this study was to determine the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and follow-up heart failure (HF) according to left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI). METHODS: This cohort study used a retrospective registry of 8169 consecutive patients discharged with a diagnosis of AMI from two university hospitals in Spain between 2010 and 2016. We used a multivariable competing risk analysis, survival-time inverse probability weighting (IPW) propensity score adjusting, and propensity score matching (PSM) to investigate the association between ACEI/ARB treatment and follow-up HF. RESULTS: During the follow-up (3.3 ± 2.2 years), 1296 patients were admitted for HF (5.2 per 100 person-years). ACEI/ARB use was not associated with fewer follow-up HF admissions in patients with LVEF > 40% (univariate analysis: sub-hazard ratio [sHR] 1.10; 95% confidence interval [CI] 0.95-1.27; p = 0.197; IPW adjusting analysis: sHR 1.11; 95% CI 0.95-1.29; p = 0.192; PSM analysis: sHR 1.12; 95% CI 0.92-1.36; p = 0.248). However, ACEI/ARB use was associated with a significant reduction in HF admission rates in patients with LVEF ≤ 40% (univariate analysis: HR 0.70; 95% CI 0.56-0.88; p = 0.003; IPW adjusting analysis: HR 0.64; 95% CI 0.50-0.83; p = 0.001; PSM analysis: HR 0.65; 95% CI 0.46-0.92; p = 0.014). CONCLUSION: Among hospitalized survivors of AMI, the use of ACEIs/ARBs was associated with a lower risk of follow-up HF in patients with LVEF ≤ 40% but not in those with LVEF > 40%. Further prospective studies are needed to confirm our results.

Coronary Artery Dominance and Long-term Prognosis in Patients With ST-segment Elevation Myocardial Infarction Treated With Primary Angioplasty.

INTRODUCTION AND OBJECTIVES: The long-term prognostic significance of coronary artery dominance pattern in patients with ST-segment elevation myocardial infarction is poorly characterized. We investigated the prognosis of such patients according to whether they had right dominance, left dominance, or codominance. METHODS: This was a retrospective study of 767 patients, who were admitted to hospital between 2007 and 2012 with ST-segment elevation myocardial infarction and treated with primary percutaneous coronary intervention. We determined the effect of the coronary dominance pattern on all-cause mortality and readmission for infarction, adjusting for mortality as a competing event. RESULTS: A total of 80.9% of patients had right coronary dominance, and 8.6% had left coronary dominance. Over 40.8 months' [interquartile range, 21.9-58.3 months] follow-up, 118 (15.4%) deaths were recorded, of which 39 (5.1%) were in hospital. Mortality for right dominance, left dominance, and codominance was 7.1%, 36.4%, and 13.8% (P ˂ .001), respectively. Cause of death was cardiovascular in 7.1%, 21.2%, and 2.4%. On Cox multivariate analysis, left dominance was significantly associated with mortality (hazard ratio = 1.76; P = .02). Taking "coronary dominance" into account in prediction of risk of death improved the discrimination and calibration capacity of GRACE (Global Registry of Acute Coronary Events) scoring. At follow-up, 9.3% (71 patients) had reinfarction. On multivariate analysis, left dominance was an independent predictor of reinfarction (subhazard ratio = 2.06; P = .01). CONCLUSIONS: In ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, left coronary artery dominance confers a higher risk of death and reinfarction than right coronary artery dominance, and should be included in prognostic stratification.

Prognostic Benefit of Beta-blockers After Acute Coronary Syndrome With Preserved Systolic Function. Still Relevant Today?

INTRODUCTION AND OBJECTIVES: The scientific evidence for using beta-blockers after acute coronary syndrome stems from studies conducted in the days before coronary revascularization and in patients with ventricular dysfunction. The aim of this study was to analyze the current long-term prognostic benefit of beta-blockers in patients with acute coronary syndrome and preserved left ventricular ejection fraction. METHODS: We conducted a retrospective cohort study of 3236 patients with acute coronary syndrome and left ventricular ejection fraction ≥ 50%. We performed a propensity-matched analysis to draw up two groups of 555 patients paired according to whether or not they had been treated with beta-blockers. The prognostic value of beta-blockers to predict mortality during follow-up was analyzed using Cox regression. RESULTS: During the follow-up (median, 5.2 years), 506 patients (15.6%) died. Patients treated with beta-blockers (n=2277 [70.4%]) had a lower mortality rate (11.6% vs 25.2%; P<.001). After propensity score matching, we found that mortality during follow-up was still lower in the beta-blocker group (14.4% vs 18.9%; P=.020). Therefore, this treatment was an independent protective factor after adjusting for confounding variables in the multivariate Cox regression analysis (hazard ratio=0.64; 95% confidence interval, 0.48-0.87; P=.004). CONCLUSIONS: Beta-blocker treatment in patients with acute coronary syndrome and preserved left ventricular ejection fraction is associated with lower long-term mortality.

Long-term Prognosis of Patients With Non-ST-segment Elevation Acute Myocardial Infarction and Coronary Arteries Without Significant Stenosis.

INTRODUCTION AND OBJECTIVES: There is debate regarding the prognostic significance of the absence of significant coronary lesions in patients with non-ST-segment elevation acute myocardial infarction. We investigated long-term prognosis in a contemporary cohort of these patients. METHODS: Retrospective observational study of 5203 patients with acute coronary syndrome. Propensity score matching was used to create 2 groups of 367 patients with non-ST-segment elevation acute myocardial infarction matched by the absence or presence of significant coronary lesions. In the matched cohort, we determined the impact of the absence of significant coronary lesions on mortality or readmission for acute coronary syndrome for 4.8 (2.6) years after discharge. RESULTS: Mortality or readmission for acute coronary syndrome was lower among patients without significant lesions (26.4% vs 32.7%; P = .09). Mortality in both groups was 19.1%. In contrast, patients without significant lesions had a lower incidence of readmission for acute coronary syndrome (2.0/100 vs 3.9/100 person-years; P = .003). The incidence of mortality or readmission for acute coronary syndrome was similar in patients without significant lesions and those with significant 1-vessel disease (26.4% vs 27.5%; P = .19), but lower than that in patients with 2-vessel disease (37.8%; P = .007) and 3-vessel disease or left main coronary artery disease (41.1%; P = .002). CONCLUSIONS: Patients with non-ST-segment elevation acute myocardial infarction and coronary arteries without significant lesions have similar long-term mortality but lower readmission rates for acute coronary syndrome than patients with significant lesions. Mortality or readmission for acute coronary syndrome is similar in patients without significant lesions and patients with 1-vessel disease, but lower than in patients with disease in 2 or more vessels.

Risk stratification for the development of heart failure after acute coronary syndrome at the time of hospital discharge: Predictive ability of GRACE risk score.

BACKGROUND: Despite encouraging declines in the incidence of heart failure (HF) complicating acute coronary syndrome (ACS), it remains a common problem with high mortality. Being able to identify patients at high risk of HF after ACS would have great clinical and economic impact. With this study, we assessed the usefulness of the GRACE score to predict HF after an ACS. METHODS: We studied 4137 consecutive patients discharged with diagnosis of ACS. We analyzed HF incidence, timing, and association with the follow-up mortality. Cox proportional hazards modeling was performed to assess the accuracy of the GRACE risk score to predict HF admissions in follow-up (median 3.1 years). RESULTS: A total of 433 patients (10.5%) developed HF. GRACE score was an independent predictor of HF after ACS [hazard ratio (HR) 1.02, 95% confidence interval (CI): 1.01-1.03, p<0.001]. A risk gradient for the development of HF with GRACE risk score was shown: high- and moderate-GRACE risk groups have been linked to a sixfold and twofold increased risk of HF. This risk gradient was maintained in patients with and without prior history of HF, in ST elevation myocardial infarction and non-ST elevation myocardial infarction groups, and in patients with depressed and preserved left ventricular ejection fraction. The development of HF was associated with high mortality (54.5% vs 13.4%; HR=4.48; 95% CI: 3.84-5.24; p<0.001). After adjusting for GRACE risk score, HF development resulted as an independent predictor of mortality. CONCLUSION: GRACE risk score has been shown to provide clinically relevant stratification of follow-up HF admission risk at the time of hospital discharge in patients with ACS.

Is 6-month GRACE risk score a useful tool to predict stroke after an acute coronary syndrome?

OBJECTIVES: The risk of stroke after an acute coronary syndrome (ACS) has increased. The aim of this study was to do a comparative validation of the 6-month GRACE (Global Registry of Acute Coronary Events) risk score and CH2DS2VASc risk score to predict the risk of post-ACS ischaemic stroke. METHODS: This was a retrospective study carried out in a single centre with 4229 patients with ACS discharged between 2004 and 2010 (66.9±12.8 years, 27.9% women, 64.2% underwent percutaneous coronary intervention). The primary end point is the occurrence of an ischaemic stroke during follow-up (median 4.6 years, IQR 2.7-7.1 years). RESULTS: 184 (4.4%) patients developed an ischaemic stroke; 153 (83.2%) had sinus rhythm and 31 (16.9%) had atrial fibrillation. Patients with stroke were older, with higher rates of hypertension, diabetes, previous stroke and previous coronary artery disease. The HR for CHA2DS2VASc was 1.36 (95% CI, 1.27 to 1.48, p<0.001) and for GRACE, HR was 1.02(95% CI, 1.01 to 1.03, p<0.001). Both risk scores show adequate discriminative ability (c-index 0.63±0.02 and 0.60±0.02 for CHA2DS2VASc and GRACE, respectively). In the reclassification method there was no difference (Net Reclassification Improvement 1.98%, p=0.69). Comparing moderate-risk/high-risk patients with low-risk patients, both risk scores showed very high negative predictive value (98.5% for CHA2DS2VASc, 98.1% for GRACE). The sensitivity of CHA2DS2VASc score was higher than the GRACE risk score (95.1% vs 87.0%), whereas specificity was lower (14.4% vs 30.2%). CONCLUSIONS: The 6-month GRACE model is a clinical risk score that facilitates the identification of individual patients who are at high risk of ischaemic stroke after ACS discharge.

Usefulness of the QRS-T angle to improve long-term risk stratification of patients with acute myocardial infarction and depressed left ventricular ejection fraction.

In light of the low cost, the widespread availability of the electrocardiogram, and the increasing economic burden of the health-related problems, we aimed to analyze the prognostic value of automatic frontal QRS-T angle to predict mortality in patients with left ventricular (LV) systolic dysfunction after acute myocardial infarction (AMI). About 467 consecutive patients discharged with diagnosis of AMI and with LV ejection fraction ≤40% were followed during 3.9 years (2.1 to 5.9). From them, 217 patients (47.5%) died. The frontal QRS-T angle was higher in patients who died (116.6±52.8 vs 77.9±55.1, respectively, p<0.001). The QRS-T angle value of 90° was the most accurate to predict all-cause cardiac death. After multivariate analysis, frontal QRS-T angle remained as an excellent predictor of all-cause and cardiac deaths, increasing the mortality 6% per each 10°. For the global mortality, the hazard ratio for a QRS-T angle>90° was 2.180 (1.558 to 3.050), and for the combined end point of cardiac death and appropriate implantable cardioverter defribrillator therapy, it was 2.385 (1.570 to 3.623). This independent predictive value was maintained even after adjusting by bundle brunch block, ST-elevation AMI, and its localization. In conclusion, a wide automatic frontal QRS-T angle (>90°) is a good discriminator of long-term mortality in patients with LV systolic dysfunction after an AMI. The ability to easily measure it from a standard 12-lead electrocardiogram together with its prognostic value makes the frontal QRS-T angle an attractive tool to help clinicians to improve risk stratification of those patients.