Persistence with long-term PCSK9 inhibitor treatment and its effectiveness in familial hypercholesterolaemia: data from the SAFEHEART study.

AIMS: Most heterozygous familial hypercholesterolaemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9is) to reach current low-density lipoprotein cholesterol (LDL-C) goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life (QoL) of PCSK9i in FH patients in clinical practice setting. METHODS AND RESULTS: Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL [interquartile range (IQR), 123-177], 3.8 mmol/L (IQR 3.2-4.6). After a median follow up of 3.7 years (IQR 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR 43-88), 1.6 mmol/L (IQR 1.1-2.23); 61 mg/dL (IQR 44-82), 1.6 mmol/L (IQR 1.1-2.1); 57.6% (IQR 39.5-69); and 58% (IQR 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77 and 48% of patients, respectively, at the last follow-up visit (P < 0.001). Mean QoL score increased slightly in the first year and remained stable. CONCLUSION: Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02693548.

Multivariate analysis for coronary heart disease in heterozygote familial hypercholesterolemia patients.

AIM: rs599839 polymorphism has been related with low levels of cholesterol and reduced coronary heart disease (CHD). METHODS: We investigated the frequency of this polymorphism in patients with heterozygous familial hypercholesterolemia (HeFH) in the Spanish familial hypercholesterolemia cohort, 230 with and 202 without CHD. Results & discussion: A lower G-allele prevalence was observed in HeFH patients with CHD with respect to controls, 35 versus 45%, respectively (p = 0.029), suggesting a protective effect. However, it was found that there was no association between rs599839 alleles and CHD in the multivariate analysis. CONCLUSION: The frequency of the protective G-allele of the rs599839 polymorphism was lower in HeFH patients with CHD compared with those HeFH patients without CHD. However, its role in HeFH may be masked by very high levels of cholesterol.

Tricuspid annular plane systolic excursion inaccuracy to assess right ventricular function in patients with previous tricuspid annulopasty.

OBJETIVES: The clinical and prognostic usefulness of tricuspid annular plane systolic excursion (TAPSE) is well established. However, the ability of TAPSE to assess right ventricular (RV) function in patients with previous tricuspid valve annulopasty is controversial. This study examined the TAPSE suitability in patients with previous tricuspid valve annuloplasty using right ventricular fractional area change (RVFAC) as reference method. METHODS: We retrospectively analyzed 53 patients who underwent tricuspid valve annuloplasty at our hospital between 2013 and 2016. TAPSE and RVFAC were obtained in preoperative and postoperative periods using standard methodology. RESULTS: Mean age was 68±12years and 34 patients (64.1%) were women. TAPSE decreased significantly after surgery in comparison with pre-surgical values (17±4.2 Vs 12.9±4.1mm, p<0.001). On the contrary, RVFAC did not change significantly after surgery (37±9.2 Vs 36.2.9, p=0.25). The correlation between RVFAC and TAPSE was better in the preoperative (r=0.63, p<0.0001) than in the postoperative period (r=0.38, P=0.005). Good intra- and interobserver agreement for TAPSE and RVFAC was obtained, with intraclass correlation coefficients of 0.97 and 0.92 for TAPSE; and 0.90 and 0.85 for RVFAC, respectively. CONCLUSIONS: These findings suggest that TAPSE is not suitable after tricuspid valve annuloplasty and it leads to an underestimation of RV systolic function. It seems to be appropriate to rely on echocardiographic parameters of global RV function such as RVFAC in this context.

Efficacy and learning curve of a hand-held echocardiography device in an oncology outpatient clinic: Expanding the use of echoscopic heart examination beyond cardiology.

Certain chemotherapy drugs for breast cancer may induce cardiotoxicity and these patients should be echocardiographically monitored. The performance of a focused echocardiographic evaluation (echoscopy) at the patient's location by a non-cardiologist appears to be feasible. The aim of the present study was to assess the accuracy of echoscopy performed by medical oncologists in an outpatient clinic using hand-held echocardiography devices. The study cohort comprised consecutive unselected patients who attended an oncology outpatient clinic. Two medical oncologists attended a one-week training period, which included theoretical and practical teaching by an expert cardiologist. Every subject underwent two echo examinations. The first examination was performed by an oncologist using a hand-held echo device and the second was performed by a cardiologist using a 'premium' device. Out of the 101 enrolled patients, 32 were men (31.7%) and the mean age was 56.03±16.88 years. There was a good global agreement [intra-class correlation coefficient (ICC): 0.65 for left ventricular ejection fraction (LVEF)]. When the results were analyzed depending on the period of time when the echo studies were performed, a clear and short learning curve was observed: LVEF started at ICC=0.58 and increased to 0.66 and 0.77 in the second and third period, respectively. There were extremely few clinically significant differences and a learning curve was also evident. In conclusion, cardiac echoscopy performed by an oncologist with a hand-held device may lead to a similar clinical management as a study performed by an expert cardiologist with a 'premium' system in patients under chemotherapy following a short training period.

Medium-term echocardiographic follow-up of systolic and diastolic left ventricular abnormalities after surgical treatment of subacute rupture.

Subacute rupture of the left ventricular free wall is a complication that occurs during the acute phase of a myocardial infarction. The subacute presentation makes surgical management possible. However, it is not known whether either pericardial manipulation or the use of pericardial patches influences left ventricular function over the medium term. Our aim was to monitor changes in left ventricular function and the development of constrictive pericarditis over the medium term in patients who had been treated surgically for subacute rupture of the left ventricle. Eleven patients with subacute rupture underwent surgery, of whom six were followed up over the medium term. A modest improvement in left ventricular systolic function was observed and there was no evidence of constrictive pericarditis. In conclusion, the surgical approach appears to be safe over the medium term and had no influence on left ventricular function. Nor did it lead to the development of constrictive pericarditis.

Chronic mitral regurgitation: a pilot study to assess preoperative left ventricular contractile function using speckle-tracking echocardiography.

BACKGROUND: The development of postoperative left ventricular (LV) dysfunction is a frequent complication in patients with chronic severe mitral regurgitation (MR) and implies a poor prognosis. The aim of this study was to evaluate the predictive value of preoperative regional LV contractile function assessment using two-dimensional echocardiography-based speckle-tracking analysis in patients with chronic severe MR. METHODS: Thirty-eight consecutive patients with chronic severe MR scheduled for mitral valve replacement were prospectively enrolled. Preoperative two-dimensional echocardiography-based speckle-tracking analysis at the level of the interventricular septum (IVS) was carried out, and strain and strain rate values were obtained. LV dP/dt and Doppler tissue imaging-derived strain and strain rate measurements were also obtained. LV volumes and LV ejection fraction (LVEF) were defined using three-dimensional echocardiography. RESULTS: Preoperative speckle tracking-derived longitudinal strain and strain rate values at the level of the IVS strongly predicted a postoperative LVEF decrease of >10%. Their predictive values were greater than those obtained for preoperative LV volumes and LVEF, LV dP/dt, and Doppler tissue imaging-derived strain and strain rate. The best discriminant parameter to detect a postoperative LVEF reduction of >10% with speckle tracking was a longitudinal strain rate at the level of the mid IVS < -0.80 s(-1) (area under the receiver operating characteristic curve, 0.88; sensitivity, 60%; specificity, 96.5%; positive predictive value, 90%; negative predictive value, 82.35%). CONCLUSIONS: IVS longitudinal speckle tracking-derived strain rate allows the accurate detection of early abnormalities in LV contractile function. It is a powerful predictor of early postoperative LVEF decreases in patients with chronic severe MR. Furthermore, speckle-tracking technology is more accurate than other methods. This new tool might assist clinicians in the optimal timing of surgery in patients with chronic severe MR.

Calcified right ventricular thrombus and antiphospholipid syndrome.

Antiphospholipid syndrome has been associated with venous and arterial thrombotic events but intracardiac thrombosis is rare. We describe a case about a 30-year-old woman, admitted with a 6-month history of arthralgia, fatigue, and intermittent fever. Subsequent investigation revealed the presence of a large and calcified mass in the right ventricular outflow tract attached to the subvalvular tricuspid apparatus. Cardiac surgery was performed and histological examination demonstrated it to be composed entirely of calcified thrombus. Screening laboratory evaluation for hypercoagulable states confirmed the diagnosis of antiphospholipid syndrome.

Left atrial myxoma prolapsing through the foramen ovale.

Very few cases have been reported of left atrial myxoma prolapsing through foramen ovale into the right atrium. This is the case of a 32-year-old woman with exertional dyspnoea and with an echocardiogram that showed a large myxoma protruding in both atriums.

Infective endocarditis: mid-term prognosis in patients with good in-hospital outcome.

BACKGROUND AND AIM OF THE STUDY: The study aim was to analyze the mid-term prognosis of infective endocarditis (IE) in patients managed with medical therapy during the in-hospital phase and who had a good initial outcome. Comparison was made with the prognosis of patients treated surgically during this period. METHODS: A total of 151 patients diagnosed with IE was studied, and in-hospital outcome, clinical characteristics and mid-term follow up data were analyzed. The main end-point was a composite of death and need for surgical repair. RESULTS: Among 151 patients, 84 (56%) underwent surgery or died during the in-hospital phase, while 67 patients (44%) received medical treatment and were discharged clinically stable with a final diagnosis of healed infective endocarditis. A better baseline profile was seen in the medically treated group, but outcome in this group showed extensive mid-term morbidity/mortality. In total, 52.2% of patients underwent surgery to correct complications and 60% died as a consequence of the disease. The event-free survival rate was 20% at five years. CONCLUSION: Despite a favorable in-hospital clinical course and successful medical treatment, patients with IE are at risk of late complications that result in a need for surgical repair, or in death. A close follow up should be made in order to treat late complications.

Impact of echocardiography in the short- and long-term prognosis of patients with infective endocarditis and negative blood cultures.

BACKGROUND AND AIM OF THE STUDY: Higher morbidity and mortality have been attributed to patients suffering endocarditis but with negative blood cultures. The study aim was to determine whether, in the present era of routine echocardiography, patients with negative-culture endocarditis had a worse short- and long-term outcome, and whether outcomes in patients with true negative and aborted positive blood cultures were different. METHODS: When endocarditis was clinically suspected, an early (<24 h) echocardiographic examination was performed in all patients, regardless of blood culture results. In total, 151 patients diagnosed with infective endocarditis (IE) comprised the study group. Among these patients, 40 (26%) had negative blood cultures, and 28 of this subgroup (70%) had received previous antibiotic therapy. Short- and long-term features and prognosis were compared between both groups. The combined main end-point was death or need for surgical repair. RESULTS: Similar anatomic and clinical characteristics were present among those patients with positive and negative cultures. In addition, mortality and need for surgery with regard to short- and long-term follow up of both groups was similar. There were no significant differences between patients with true- or aborted-negative cultures in terms of short- and long-term prognosis. CONCLUSION: No differences in short- and long-term prognosis were seen among patients with IE and positive versus negative blood cultures. The prognosis was also similar between those with true negative culture versus aborted negative cultures. Early echocardiography in patients with clinically suspected IE may have changed the outcome in patients with negative cultures.

Negative predictive value of dipyridamole vs. dobutamine stress echocardiography in the long-term follow-up of patients undergoing major vascular surgery.

INTRODUCTION: Perioperative cardiovascular complications are a significant cause of post-surgical morbidity and mortality in patients undergoing major vascular surgery (MVS). Dobutamine stress echocardiography is the most important method of detecting coronary artery disease in these patients. Although dipyridamole stress echocardiography (SE-DIP) and dobutamine stress echo (SE-DOB) have demonstrated similar negative predictive value (NPV) in the early postoperative period in patients undergoing MVS, there are few data concerning the negative predictive value of SE-DIP in the long-term follow-up of this subgroup of patients. OBJECTIVE: Our aim was to compare the long-term NPV of these two types of stress echocardiography and to compare it with perioperative NPV, based on the working assumption that they are similar. PATIENTS AND METHODS: A retrospective study was made of 157 patients based on preoperative evaluations for vascular surgery between February 1997 and February 2000. Clinical history and the results of consecutive stress exams were analyzed. We excluded patients with a positive stress echo and those that performed dobutamine stress echo which was considered inconclusive since they did not reach 85% of the maximum heart rate for their age. Therefore, 110 patients were included, 29 (26.4%) with dobutamine and 81 (73.6%) dipyridamole-atropine. The patients were followed after surgery for a period of 2.2 +/- 1 years. Cardiac events were defined as cardiac death, nonfatal acute myocardial infarction and hospitalization for unstable angina. The cumulative probability of event-free survival was compared. RESULTS: The patients' mean age was 65 +/- 10 years, and 108 (98.1%) were men. After 2.2 +/- 1 years of follow-up, 7 cardiac events occurred in the group with negative SE-DIP (8.6%) and 3 in patients with negative SE-DOB (10.3%). There were no statistically significant differences between the two groups concerning event-free survival (3.7 +/- 0.2 vs. 3.5 +/- 0.2 years for SE-DIP and SE-DOB respectively; p = 0.91). Negative predictive values for SE for perioperative and long-term cardiac events were 97.3% and 90.9% respectively. CONCLUSIONS: SE-DIP is a good alternative to SE-DOB in the preoperative evaluation of patients undergoing MVS, with the NPV of SE-DIP being similar to SE-DOB in the perioperative period and in long-term follow-up.