Polypill Strategy in Secondary Cardiovascular Prevention.

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

Efficacy and safety of transcatheter valve-in-valve replacement for Mitroflow bioprosthetic valve dysfunction.

OBJECTIVES: Bioprostheses with pericardial leaflets mounted externally on the stent pose a high risk for valve-in-valve (ViV) procedures. This study analyzed the efficacy and safety of ViV procedures for treating structural valve deterioration (SVD) in Mitroflow bioprostheses. METHODS: Between January 2012 and August 2017, 11 patients (mean age 80.3 ± 5.6 years) were treated for SVD of Mitroflow bioprostheses with transcatheter ViV procedures (six transapical [TA] and five transfemoral [TF]) using balloon expandable bioprostheses. RESULTS: All patients but one were in NYHA class III-IV. Mean STS PROM, euroSCORE I, and euroSCORE II were 8 ± 6.5%, 27.8 ± 11.5%, and 12 ± 5.9%, respectively. Two patients had a "porcelain aorta." The size of implanted valves were 23 mm in 10 cases and 26 mm in one case. One patient suffered a coronary occlusion during a TF approach. The mean volume of contrast used in TF implants was 163 ± 69.8 mL. No contrast media were used in TA procedures. There was one in-hospital death (10%). At 1 year of follow-up, peak and mean aortic gradients were 25.5 ± 5.8 mmHg and 15.5 ± 5.7 mmHg, respectively. One patient had mild paravalvular regurgitation. Cumulative survival was 90.9% at 1 year, 70.7% at 2 years, and 53% at 3 years. CONCLUSIONS: ViV procedures with balloon-expandable aortic valves provide good hemodynamic and clinical mid-term results for treating patients with a degenerated Mitroflow aortic bioprosthesis. Special care must be taken in small aortic roots, when the stented valve is in the supra-annular position to avoid coronary ostial obstruction.

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Introduction and objectives: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Methods: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Results: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Conclusion: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

[Survival impact of previous statin therapy in patients hospitalized with COVID-19]. / Impacto del tratamiento previo con estatinas sobre la supervivencia de los pacientes hospitalizados con COVID-19.

INTRODUCTION: Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital. METHODS: We conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days. RESULTS: We studied 1122 hospitalized patients with COVID-19, whose median age was 71years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76; 95%CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32; 95%CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45; 95%CI: 0.28-0.73). CONCLUSIONS: Our study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease.

Survival impact of previous statin therapy in patients hospitalized with COVID-19.

Introduction: Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital. Methods: We conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days. Results: We studied 1122 hospitalized patients with COVID-19, whose median age was 71 years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76; 95% CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32; 95% CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45; 95% CI: 0.28-0.73). Conclusions: Our study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease.

Introducción: El tratamiento con estatinas podría presentar un efecto pronóstico beneficioso en pacientes con COVID-19, dadas sus propiedades inmunomoduladoras, antiinflamatorias y estabilizadoras de la placa de ateroma. Nuestro propósito fue analizar esta hipótesis tomando como base el registro de COVID-19 de un hospital universitario español. Métodos: Realizamos un estudio observacional y retrospectivo en el que se incluyeron los pacientes hospitalizados con COVID-19 diagnosticado mediante PCR entre marzo de 2020 y octubre de 2020 en un centro. Mediante regresión logística, diseñamos una puntuación de propensión para estimar la probabilidad de que un paciente recibiese tratamiento con estatinas antes del ingreso. Comparamos la supervivencia de los pacientes con y sin tratamiento con estatinas mediante la regresión de Cox ponderada por la inversa de la probabilidad de recibir el tratamiento (IPT). La mediana de seguimiento fue de 406 días. Resultados: Estudiamos 1.122 pacientes hospitalizados con COVID-19, cuya mediana de edad era de 71 años y de los cuales 488 (43,5%) eran mujeres. 451 (40,2%) pacientes recibían estatinas antes del ingreso. En el análisis de supervivencia ponderado por la IPT, el tratamiento previo con estatinas se asoció a una reducción significativa de la mortalidad (HR: 0,76; IC 95%: 0,59­0,97). El mayor beneficio del tratamiento previo con estatinas se observó en los subgrupos de pacientes con enfermedad arterial coronaria (HR: 0,32; IC 95%: 0,18­0,56) y enfermedad arterial extracardiaca (HR: 0,45; IC 95%: 0,28­0,73). Conclusiones: Nuestro estudio mostró una asociación significativa entre el tratamiento previo con estatinas y una menor mortalidad en pacientes hospitalizados con COVID-19. El beneficio pronóstico observado fue mayor en los pacientes con enfermedad aterosclerótica coronaria o extracardiaca previa.

Soluble HLA-G levels in heart transplant recipients: Dynamics and correlation with clinical outcomes.

PURPOSE: To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes. METHODS: Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years. RESULTS: Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population. CONCLUSIONS: Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.

Additive prognostic and diagnostic value of diastolic exercise parameters in patients referred for exercise echocardiography.

AIMS: Exercise echocardiography (ExE) may evaluate left ventricular (LV) systolic and diastolic function. We aimed to assess the value of diastolic parameters at exercise [early LV inflow velocity to early tissue Doppler annulus velocity (E/e')] in patients with normal or abnormal resting diastolic function (DF) referred for a clinically indicated ExE. METHODS AND RESULTS: LV systolic and DF according to ASE/EACVI guidelines and mitral regurgitation (MR) were evaluated at rest in 772 patients (age 67 ± 12 years) with preserved LV ejection fraction (LVEF ≥ 50%). We assessed regional/global LV systolic function at peak exercise, while MR and E/e' where evaluated in the immediate post-exercise period. Abnormal ExE was defined as ischaemia or fixed wall motion abnormalities, and raised E/e' values as >15 at rest and at exercise (e' at the septal level). Patients were grouped as complaining or not of dyspnoea. Events were overall mortality, myocardial infarction, admission for unstable angina or cardiac failure, and coronary revascularization. DF was abnormal at rest in 221 patients (29%) and indeterminate in 77 (10%), with similar percentages in patients with and without dyspnoea. Exercise E/e' >15 was found in 37% of patients with abnormal DF, 21% with indeterminate DF, and 6% with normal DF (P < 0.001). Patients with abnormal ExE had more often abnormal resting DF (39% vs. 25%, P = 0.001) and exercise E/e' >15 (25% vs. 13%, P < 0.001) than those with normal ExE. During a median follow-up of 1.68 years, there were 132 events. Independent predictors included peak exercise LVEF [hazard ratio (HR) = 0.93, 95% confidence interval (CI) = 0.91-0.94, P < 0.001], and exercise E/e' (HR= 1.04, 95% CI = 1.01-1.07, P = 0.01). Neither resting E/e' values nor resting abnormal DF by ASE/EACVI guidelines, were independent predictors. Annualized event-rates were 43.2% in patients with (+) ExE plus (+) exercise E/e', 23.8% in those with (+) ExE and (-) exercise E/e', 7.9% in (-) ExE and (+) exercise E/e', and 3.6% with both variables normal. CONCLUSIONS: The results of diastolic dysfunction at rest and at exercise were similar between patients with or without dyspnoea referred for ExE, but they were associated with abnormal ExE. Exercise E/e' reclassified 21% of patients with indeterminate DF and further predicted outcome on top of ExE results.

Real world comparison of spironolactone and eplerenone in patients with heart failure.

AIMS: In the absence of previous direct comparative studies, we aimed to evaluate the effectiveness of spironolactone and eplerenone in patients with heart failure and reduced ejection fraction (HFrEF) in a real-world clinical setting. METHODS: Using Fine-Gray´s competing risk regression, we compared the clinical outcomes of 293 patients with chronic HF and left ventricular ejection fraction <40% treated with eplerenone and 293 propensity-score matched individuals treated with spironolactone. Study subjects were selected from a prospective cohort of 1404 ambulatory patients with HFrEF seen since 2010 to 2019 in a single specialized HF clinic, among which 992 received a mineralocorticoid receptor antagonist at baseline. Median follow-up was 3.95 years. RESULTS: No statistically significant differences between patients treated with eplerenone versus spironolactone were observed with regard to the risk of the primary composite end-point cardiovascular death or HF hospitalization (HR 0.95; 95% CI 0.73-1.23; p= 0.677). However, eplerenone use was associated to lower cardiovascular mortality (HR 0.55; 95% CI 0.35-0.85; p= 0.008) and lower all-cause mortality (HR 0.67; 95% CI 0.47-0.95; p= 0.027). The incidence of drug suspension due to side effects (HR 0.58, 95% CI 0.40-0.85; p= 0.005) and drug suspension due to any reason (HR 0.70, 95% CI 0.51-0.97; p= 0.033) were lower among patients treated with eplerenone. CONCLUSIONS: In this observational, real-world, propensity-score matched study of patients with HFrEF, eplerenone was associated to lower cardiovascular mortality and lower all-cause mortality than spironolactone.

Cancer in patients with heart failure: Incidence, risk factors and prognostic impact.

AIMS: To assess the incidence of cancer diagnosis and cancer-related mortality in patients with heart failure (HF). METHODS: Observational study based in a prospective cohort of patients with HF referred to a specialized Spanish clinic between 2010 and 2019. The observed incidence of malignancies (excluding non-melanoma skin cancer) was compared to that expected for the general Spanish population according to the Global Cancer Observatory. RESULTS: We studied 1909 consecutive patients with HF. Over a median follow-up of 4.07 years, 165 new cases of malignancy were diagnosed. Observed age-standardized incidence rates of cancer were 861 (95% CI 618.4-2159.4) cases per 100,000 patients-years in men and 728.5 (95% CI 451.1-4308.7) cases per 100,000 patients-years in women; while age-standardized incidence rates of cancer expected for the general Spanish population were 479.4 cases per 100,000 patients-years in men (risk ratio = 1.80) and 295.5 cases per 100,000 patients-years in women (risk ratio = 2.46). Both a history of pre-existing malignancy at baseline and the development of new malignancies during follow-up were associated with reduced survival. Observed age-standardized cancer-related mortality was 344.1 (95% CI 202.1-1675) deaths per 100,000 patient-years in men and 217.0 (95% CI 32.8-3949.3) deaths per 100,000 patient-years in women; while age-standardized cancer-related mortality expected for the general Spanish population was 201.4 deaths per 100,000 patients-years in men (risk ratio = 1.71) and 96.2 deaths per 100,000 patients-years in women (risk ratio = 2.26). CONCLUSION: Patients with HF showed higher incidence rates of cancer diagnosis and cancer-related mortality than those expected for the general population.

Balloon-expanding transcatheter aortic valve implantation for degenerated Mitroflow bioprostheses: clinical and echocardiographic long-term outcomes.

OBJECTIVES: This study aims to analyse the risks associated with valve-in-valve procedures for treating structural valve deterioration in Mitroflow bioprostheses, as well as to determine the impact of the original Mitroflow size on the patients' long-term outcomes. METHODS: Between January 2012 and September 2019, 21 patients (61.9% males; mean age 82.4 ± 5.4 years) were treated for Mitroflow deterioration with valve-in-valve procedures (12 transapical and 9 transfemoral). RESULTS: Mean EuroSCORE I and EuroSCORE II were 28.2% ± 13.6% and 10.5% ± 6.1%, respectively. Six patients presented an indexed aortic root diameter <14 mm/m2 and 7 patients a diameter of sinus of Valsalva <30 mm. Implanted transcatheter valve sizes were 20 mm in 6 cases, 23 mm in 14 cases and 26 mm in 1 patient. A Valve Academic Research Consortium-2 complication occurred in 23.8% of cases, including 3 coronary occlusions. In-hospital mortality was 9.5%. The 20 mm transcatheter valves presented significantly higher postoperative peak and mean aortic gradients than other sizes (54.1 ± 11.3 mmHg vs 29.9 ± 9.6 mmHg, P = 0.003; and 29.3 ± 7.7 mmHg vs 17.4 ± 5.9 mmHg, P = 0.015, respectively). There were 12 cases of patient-prosthesis mismatch (57.1%) and 3 cases (14.3%) of severe patient-prosthesis mismatch. Cumulative survival was 85.7% ± 7.6% at 1 year, 74.3% ± 10% at 2 years and 37.1% ± 14.1% at 5 years. CONCLUSIONS: Valve-in-valve procedures with balloon-expandable transcatheter valves associate a high risk of coronary occlusion in patients with indexed aortic root diameter <14 mm/m2 and low coronary ostia <12 mm. Valve-in valve procedures with 20 mm balloon-expandable transcatheter valves in ≤21 mm Mitroflow bioprosthesis leave significant residual transvalvular gradients that might obscure patients' long-term outcomes.

Light chain and transthyretin cardiac amyloidosis: Clinical characteristics, natural history and prognostic factors. / Amiloidosis cardíaca por cadenas ligeras y por transtirretina: características clínicas, historia natural y predictores pronósticos.

INTRODUCTION AND OBJECTIVES: Light-chain amyloidosis (AL-CA) and transthyretin amyloidosis (ATTR-CA) are the most common types of cardiac amyloidosis (CA). We sought to study the clinical characteristics and prognosis of both diseases. METHODS: We conducted a single-centre, retrospective review of all patients diagnosed with CA between 1998 and 2018. Clinical characteristics, complementary tests, survival and other adverse clinical events were studied. RESULTS: We identified 105 patients with CA, 65 ATTR-CA and 40 AL-CA. Mean age was 74.4 years; 24.8% were women. In both groups, heart failure was the most frequent clinical presentation (55.2%). The most prevalent electrocardiographic findings were the pseudoinfarct pattern (68.5%) and a Sokolow-Lyon index < 1.5 mV (67.7%), with no differences between the two subtypes of CA. One-year, 3-year, and 5-year survival was 43.3%, 40.4% and 35.4%, respectively, in AC-AL patients, and 85.1%, 57.3% and 31.4% in AC-ATTR patients (p = 0.004). AL-CA subtype (HR 3.41; 95% CI 1.45-8.06; p = 0.005), previous admission for heart failure (HR 4.25; 95% CI 1.63-11.09; p = 0.003) and a NYHA class III-IV (HR 2.76; 95% CI; 1.09-7.03; p = 0.033) were independent predictors of mortality, while beta-blocker therapy was associated with longer survival (HR 0.23; 95% CI 0.09-0.59; p = 0.002). CONCLUSIONS: Differences exist between the clinical presentation of AL-CA and ATTR-CA patients. Both diseases, particularly AL-CA, are associated with poor life prognosis.

Abnormal exercise echocardiography plus abnormal E/e' ratio at exercise portends worse outcome in patients with dyspnea.

BACKGROUND: The role of exercise echocardiography (ExE) for the assessment of patients with dyspnea is promising. We aimed to analyze the clinical characteristics and outcome of patients with this condition referred for ExE. METHODS: A total of 505 patients (66 ± 11 years, 57% women) referred for evaluation of dyspnea were considered. Mitral regurgitation, ratio of early left ventricular inflow wave to early diastolic annulus wave (E/e'), and wall motion abnormalities (WMAs) were measured at rest and at exercise. Considered events were overall mortality, non-fatal myocardial infarction, late revascularization, and admission for heart failure. RESULTS: Ischemia was observed in 102 patients (20%), whereas WMAs were already present at rest in 55 patients (11%). A percent achieved of predicted metabolic equivalents >100% was found for most of the patients (70%). During a median follow-up of 3.50 years, 66 patients had events (annualized event rate 3.5%). An E/e' value of 13 at post-exercise was the best cut-off value to predict events. After adjustment by clinical and ExE variables, the combination of an abnormal ExE and E/e' values at post-exercise ≥13 was an independent predictor of events (hazard ratio = 3.67, 95% confidence interval = 2.11-6.38, p < 0.001). The worse outcome corresponded to patients with abnormal ExE and raised E/e' values at post-exercise (annualized event rate 17.2%). Patients with normal E/e' values at post-exercise had better outcome irrespective of the ExE results (annualized event rate 2.2% with normal ExE and 2.9% with abnormal ExE), whereas patients with high E/e' values at post-exercise but normal ExE results were at intermediate risk (annualized event rate 5.0%). CONCLUSIONS: Despite favorable ExE results, event rate remains high among patients with dyspnea referred for ExE, which may have a role to predict outcome in this setting. Patients with both raised E/e' values at post-exercise and abnormal ExE results are at the highest event risk.

Value of the coronary artery disease consortium rule in patients with acute chest pain and negative troponins referred for exercise stress testing.

OBJECTIVE: To assess the value of the pretest probability (PTP) of coronary artery disease (CAD) for predicting stress testing results and coronary events in patients with acute chest pain and negative troponins. PATIENTS AND METHODS: A total of 3527 patients without a history of CAD referred to our chest pain unit with suspected acute coronary syndromes, nondiagnostic ECGs, and negative troponin levels underwent exercise stress testing. PTP was estimated with the CAD consortium prediction rule, and was categorized as low (<15%), low-intermediate (15-65%), intermediate-high (66-85%), and high (>85%). The endpoints were the presence of signs of inducible myocardial ischemia on stress testing and the occurrence of coronary events within 6 months. RESULTS: The probability of exercise-induced myocardial ischemia was 2.6, 12.6, 42.9, and 82.1% in patients with low, low-intermediate, intermediate-high, and high PTP, respectively (Ptrend<0.001). The cumulative rate of coronary events within 6 months was also significantly lower in patients with low PTP of CAD (0.8%) than in those with low-intermediate (6.9%), intermediate-high (32.5%), or high PTP (66.7%) (Ptrend<0.001). Per 10% increment in PTP of CAD, the adjusted odds ratios for inducible myocardial ischemia and coronary events within 6 months were, respectively, 1.71 (95% confidence interval: 1.61-1.85) and 1.87 (95% confidence interval: 1.74-2.01). CONCLUSION: PTP was associated strongly with the likelihood of exercise-induced myocardial ischemia and coronary events in patients with suspected acute coronary syndromes and negative troponins. The yield of stress testing in the subset of patients with low PTP was very low.

Late graft failure in heart transplant recipients: incidence, risk factors and clinical outcomes.

AIM: To analyse the incidence, risk factors and clinical outcomes of late graft failure after heart transplantation. METHODS AND RESULTS: We conducted an observational, single-centre study based on 547 patients who underwent cardiac transplantation from 1991 to 2014 and who survived the in-hospital postoperative period. Late graft failure was defined as the first hospitalization due to this condition after discharge. Over a mean follow-up of 8.4 ± 6 years, 178 (32.5%) patients were hospitalized due to late graft failure [incidence rate: 3.6 cases per 100 patient-years, 95% confidence interval (CI) 3.1-4.2]. Pre-transplant diabetes, higher pre-transplant transpulmonary pressure gradient and lower donor-recipient weight ratio were independently associated with higher risk of graft failure. Cardiac allograft vasculopathy, cellular rejection grade ≥1R, and antibody-mediated rejection grade ≥1 were detected in 50.6%, 44.9% and 19.2% patients, respectively, admitted due to graft failure. Left ventricular ejection fraction was ≥50% in 60.1% of these patients. Re-transplant free survival 1, 5, 10 and 15 years after the diagnosis of late graft failure was 72.2%, 38.4%, 18.4%, and 7.5%, respectively; the incidence rate of re-hospitalization due to decompensated heart failure was 40.9 episodes per 100 patient-years (95% CI 36.6-46.1). The need for inotropes, the presence of cardiac allograft vasculopathy, higher creatinine serum levels, lower ejection fraction and lower sodium serum levels were independent predictors of worse outcomes. CONCLUSIONS: Late graft failure is frequent after heart transplantation, as it is associated with poor outcomes. Rejection and cardiac allograft vasculopathy are the most frequent underlying causes.

Left ventricular torsion and circumferential strain responses to exercise in patients with ischemic coronary artery disease.

LV torsion during exercise in patients with coronary artery disease (CAD) is not well known. Circumferential strain (CS) and left ventricular (LV) torsion (Tor) have not been evaluated during ischemia in these patients. We aimed to assess the effect of ischemia during exercise echocardiography (ExE) on CS and Tor. We studied a group of 73 patients with true positive ExE results (Ischemic group: ischemia plus an abnormal coronary angiogram) and a matched control group of 66 patients with negative ExE and either normal coronary angiography or low post-test probability of CAD. Basal rotation (Rot) and apical rotation and basal and apical CS were studied by speckle tracking at rest and exercise. Apical CS and apical and basal Rot values were similar between groups at rest, except basal CS which was already worse in the ischemic group. At exercise, all rotational and CS parameters were impaired in the ischemic in comparison with the control group (basal CS: -18 ± 5 vs. -25 ± 7 %, p < 0.001; apical CS: -31 ± 11 vs. - 43 ± 9 %, p < 0.001; time to basal CS: 52 ± 6 vs. 48 ± 7 %, p = 0.001; time to apical CS: 55 ± 7 vs. 49 ± 6 %, p < 0.001; basal rotation: -0.7 ± 6.5° vs. -6.2 ± 8.5°, p < 0.001; LV twist 13.0 ± 10.4° vs.19.7 ± 11.5°, p < 0.001; LV-Tor 1.9 ± 1.6°/cm vs. 2.8 ± 1.7˚/cm, p = 0.001) with the exception of apical rotation which was similar (12.3 ± 7.4° vs. 13.4 ± 7.7°, p = NS). Basal and apical CS and basal rotation impair during exercise-induced ischemia. LV-Tor decreases with ischemia due to worsening of basal rotation, whereas apical rotation does not impair, suggesting the existence of an apical compensatory mechanism.

Outcome by Exercise Echocardiography in Patients with Low Pretest Probability of Coronary Artery Disease.

BACKGROUND: Recommendations for testing in patients with low pretest probability of coronary artery disease differ in guidelines from no testing at all to different tests. The aim of this study was to assess the value of exercise echocardiography (ExE) to define outcome in this population. METHODS: A retrospective analysis was conducted of 1,436 patients with low pretest probability of coronary artery disease (<15%) who underwent initial ExE. Overall mortality, major adverse cardiac events (MACEs), defined as cardiac death or nonfatal myocardial infarction, and revascularization during follow-up, were assessed. Ischemia (development of new wall motion abnormalities with exercise) and fixed wall motion abnormalities were measured. RESULTS: The mean age was 50 ± 12 years. Resting wall motion abnormalities were seen in 13 patients (0.9%) and ischemia in 108 (7.5%). During follow-up, 38 patients died, 10 of cardiac death (annualized death rate, 0.39%); 20 patients had MACEs (annualized MACE rate, 0.21%); and 48 patients (29 with ischemia) underwent revascularization (annualized revascularization rate, 0.51%). The number and percentage of MACEs in the abnormal and normal ExE groups were similar (two [1.7%] vs 18 [1.4%], P = .70), as was the annualized MACE rate (0.31% vs 0.21%, P = .50). Peak left ventricular ejection fraction exhibited a nonsignificant trend for predicting MACEs (P = .11). The number of studies needed to detect an abnormal finding was 12.6 and to detect a patient with extensive ischemia was 26.1. CONCLUSIONS: ExE offers limited prognostic information in patients with low pretest probability of coronary artery disease. The small number of abnormal findings on ExE and low event rates and the large number of studies needed to detect an abnormal finding limit further the value of imaging in this population.

Toxoplasma Gondii Serostatus in Heart Transplant Recipients: Is It an Independent Prognostic Factor?

INTRODUCTION AND OBJECTIVES: To assess the potential association between recipient Toxoplasma gondii serostatus and outcomes after heart transplant (HT). METHODS: We conducted a retrospective single-center study of 657 HT recipients from 1991 to 2015. Survival and the incidence of adverse clinical events of T. gondii-seropositive (n = 481) vs T. gondii-seronegative (n = 176) recipients were compared by means of 2 different multivariable Cox regression models. Model 1 included solely age and sex, and model 2 included other potential confounders. RESULTS: Over a median follow-up of 2903 days (interquartile range: 898-4757), 250 seropositive recipients (52%) and 72 seronegative recipients (41%) died. Univariable analysis showed increased posttransplant mortality among T. gondii-seropositive recipients (hazard ratio [HR] = 1.31; 95% confidence interval [95%CI], 1,00-1.70). After multivariable adjustment, the statistical significance of this association was lost (model 1: HR = 1.09; 95%CI, 0.83-1.43; model 2:HR = 1.12; 95%CI, 0.85-1.47). Recipient T. gondii seropositivity was independently associated with an increased risk of acute rejection (model 1: HR = 1.36; 95%CI, 1.06-1.74; model 2: HR = 1.29; 95%CI, 1.01-1.66). Multivariable models showed no statistically significant impact of recipient T. gondii serostatus on the incidence of infection, malignancy, coronary allograft vasculopathy, or the composite outcome of cardiac death or retransplant. No significant association was found between donor-recipient T. gondii serostatus matching and posttransplant outcome. CONCLUSIONS: In this study, recipient T. gondii serostatus was not an independent predictor of long-term post-HT outcome.