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.

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.

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.).

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.

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.

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.

Effect of stent thrombosis on the risk-benefit balance of drug-eluting stents and bare metal stents.

INTRODUCTION AND OBJECTIVES: To determine the difference in the risk of stent thrombosis between drug-eluting stents (DES) and bare-metal stents (BMS) and to assess the clinical implications. METHODS: A retrospective analysis of two cohorts of patients treated at our center with either > or =1 paclitaxeleluting stents (PES) (n=430) or > or =1 BMSs (n=1230) during 2003-2004 was carried out using propensity score methods to compare the adjusted risks of stent thrombosis, instent restenosis, cardiovascular death, acute myocardial infarction (AMI), and target-lesion revascularization with the two stent types. RESULTS: After a median follow-up of 46 months, there was a higher risk of stent thrombosis in PESs (hazard ratio [HR]=3; 95% confidence interval [CI], 1.2-7.1] though the risk of in-stent restenosis was lower (HR=0.3; 95% CI, 0.2-0.7]. There was no difference in the risk of cardiovascular death, AMI or target-lesion revascularization. With PESs, the risks of target-lesion revascularization (HR=0.33; 95% CI, 0.2-0.7) and in-stent restenosis (HR=0.32; 95% CI, 0.2-0.7) were reduced during the first year of follow-up. After this time, the risks of target-lesion revascularization (HR=1.8; 95% CI, 1-3.2) and very late stent thrombosis (HR=12.8; 95% CI, 3-55.1) both increased. CONCLUSIONS: Our findings indicate that the balance of risks and benefits of PESs compared with BMSs is different in the early and late periods after stent implantation. The greatly increased risk of very late stent thrombosis in PESs could cancel out the clinical benefits associated with the reduction in in-stent restenosis observed in PESs relative to BMSs.

Statin therapy and contrast-induced nephropathy after primary angioplasty.

A recent study suggested that statin therapy may prevent contrast-induced nephropathy (CIN) following primary angioplasty. Our aim was to assess the effect of statins in this setting in a larger population. We evaluated 589 consecutive patients with acute myocardial infarction who underwent primary angioplasty at our institution. Contrast-induced nephropathy was defined as an increase in serum creatinine by > or =0.5 mg/dL within 72 h following the procedure. Overall, 69 patients (11.9%) developed CIN. The incidence of CIN in the group on statins was 15.9%, as compared with 10.8% in the group not taking statins (p=0.2). Thus, we did not observe a protective effect of statin therapy on CIN development after primary angioplasty.

[Transradial approach to coronary angiography and angioplasty: initial experience and learning curve]. / Coronariografía y angioplastia coronaria por vía radial: experiencia incial curva de aprendizaje.

INTRODUCTION: The transradial approach has emerged as an attractive alternative to the femoral approach for coronary angiography and interventions. We describe our experience with the transradial approach and analyze the influence of the learning curve. PATIENTS AND METHODS: The transradial approach was attempted in patients with a good radial pulse and normal Allen test. When feasible and clinically indicated, we attempted ad hoc intervention. We divided the study population into two groups: Group A (the first 200 cases) and B (all other patients). We compared the radial group with a matched femoral control group. RESULTS: We attempted the transradial approach in 526 patients (77.6% male; age 63.5 +/- 11.51), and obtained a success rate of 93.7%. We found differences between group A and B in the success rate (91.0 vs 95.4%, p = 0,04), duration of procedure [23 (16-29) vs. 19 (15-24) minutes; p < 0.001], and fluoroscopy time [6.4 (4.2-10) vs. 5.0 (3.0-7.7) minutes; p < 0,001]. At 24 h of follow-up, we found small hematomas in 9.4%, bleeding in 4.9%, and radial artery obstruction in 2.8%, with no cases of arteriovenous fistula, pseudoaneurysm, or need for vascular surgery. We attempted intervention in 169 patients with 258 lesions, achieving angiographic success in 96.1%. We found no differences in the characteristics of the lesions and patients, or in the angiographic success rate of the radial and femoral PTCA groups. CONCLUSIONS: The transradial approach is a safe and effective alternative to femoral catheterization. There is a significant learning curve associated with the successful performance of transradial procedures.