Incremental prognostic value of lung ultrasound on contemporary heart failure risk scores.

Introduction: Over the last decades, several scores have been developed to aid clinicians in assessing prognosis in patients with heart failure (HF) based on clinical data, medications and, ultimately, biomarkers. Lung ultrasound (LUS) has emerged as a promising prognostic tool for patients when assessed at discharge after a HF hospitalization. We hypothesized that contemporary HF risk scores can be improved upon by the inclusion of the number of B-lines detected by LUS at discharge to predict death, urgent visit, or HF readmission at 6- month follow-up. Methods: We evaluated the discrimination improvement of adding the number of B-lines to 4 contemporary HF risk scores (Get with the Guidelines -GWTG-, MAGGIC, Redin-SCORE, and BCN Bio-HF) by comparing the change in the area under the receiver operating curve (AUC), the net reclassification index (NRI), and the integrated discrimination improvement (IDI). The population of the study was constituted by the 123 patients enrolled in the LUS-HF trial, adjusting the analyses by the intervention. Results: The AUC of the GWTG score increased from 0.682 to 0.789 (p = 0.02), resulting in a NRI of 0.608 and an IDI of 0.136 (p < 0.05). Similar results were observed when adding the number of B-lines to the MAGGIC score, with an AUC that increased from 0.705 to 0.787 (p < 0.05). This increase translated into a NRI of 0.608 and an IDI of 0.038 (p < 0.05). Regarding Redin-SCORE at 1-month and 1-year, the AUC increased from 0.714 to 0.773 and from 0.681 to 0.757, although it did not reach statistical significance (p = 0.08 and p = 0.06 respectively). Both IDI and NRI were significantly improved (0.093 and 0.509 in the 1-month score, p < 0.05; 0.056 and 0.111 in the 1-year score, p < 0.05). Lastly, the AUC for the BCN Bio-HF score increased from 0.733 to 0.772, which was statistically non-significant, with a NRI value of 0.363 (p = 0.06) and an IDI of 0.092 (p < 0.05). Conclusion: Adding the results of LUS evaluated at discharge improved the predictive value of most of the contemporary HF risk scores. As it is a simple, fast, and non-invasive test it may be recommended to assess prognosis at discharge in HF patients.

Indications, Complications, and Outcomes of Cardiac Surgery After Heart Transplantation: Results From the Cash Study.

Background: Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports. Methods: We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate. Results: Data were available from 19 centers in North America (n = 7), South America (n = 1), and Europe (n = 11), with a total of 110 patients. A median of 3 (IQR 2-8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (n = 62), coronary artery disease (CAD) (n = 16), constrictive pericarditis (n = 17), aortic pathology (n = 13), and myxoma (n = 2). The median age at CASH was 57.7 (47.8-63.1) years, with a median time from transplant to CASH of 4.4 (1-9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8-14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively. Conclusion: Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure.

The Benefits of Early versus Late Therapeutic Intervention in Fabry Disease.

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants of the GLA gene. Heterozygous female patients may show much more variability in clinical manifestations, ranging from asymptomatic to full-blown disease. Because of this heterogeneous clinical picture in women, the diagnosis of FD has typically been delayed for more than a decade, and the optimal time to initiate treatment remains controversial. Case Presentation. Here, we present two unrelated female patients diagnosed with FD harbouring the same pathogenic GLA variant. We discuss the implications of initiating specific therapy at different stages of the disease, with and without organ involvement (early versus late therapeutic intervention). Conclusions: These clinical cases suggest that initiating specific treatment at an earlier age in women with FD may prevent organ involvement and associated clinical events.

A Simple Score to Identify Super-Responders to Sacubitril/Valsartan in Ambulatory Patients With Heart Failure.

INTRODUCTION: Sacubitril/valsartan (SV) promotes cardiac remodeling and improves prognosis in patients with heart failure (HF). However, the response to the drug may vary between patients and its implementation in daily clinical practice has been slower than expected. Our objective was to develop a score predicting the super-response to SV in HF outpatients. METHODS: This is a retrospective analysis of 185 consecutive patients prescribed SV from two tertiary hospitals between September 2016 and February 2018. Super-responder was defined as a patient taking the drug and (i) without HF admissions, death, or heart transplant, and (ii) with a ≥50% reduction in NT-proBNP levels and/or an increase of ≥10 points in LVEF in a 12-month follow-up period after starting SV. Clinical, echocardiographic, ECG, and biochemical variables were used in a logistic regression analysis to construct a score for super-response to SV which was internally validated using bootstrap method. RESULTS: Out of 185 patients, 65 (35%) fulfilled the super-responder criteria. Predictors for super-response to SV were absence of both previous aldosterone antagonist and diuretic treatment, NYHA I-II class, female gender, previous 1-year HF admission, and sinus rhythm. An integrating score distinguished a low- (<25%), intermediate- (∼46%), and high-probability (>80%) for 1-year super-response to SV. The AUC for the model was 0.72 (95%CI: 0.64-0.80), remaining consistent after internal validation. CONCLUSION: One-third of our patients presented a super-response to SV. We propose an easy-to-calculate score to predict super-response to SV after 1-year initiation based on variables that are currently assessed in clinical practice.

Interdisciplinary Mobile Health Model to Improve Clinical Care After Heart Transplantation: Implementation Strategy Study.

BACKGROUND: Solid organ transplantation could be the only life-saving treatment for end-stage heart failure. Nevertheless, multimorbidity and polypharmacy remain major problems after heart transplant. A technology-based behavioral intervention model was established to improve clinical practice in a heart transplant outpatient setting. To support the new strategy, the mHeart app, a mobile health (mHealth) tool, was developed for use by patients and providers. OBJECTIVE: The primary objective of this study was to describe the implementation of the mHeart model and to outline the main facilitators identified when conceiving an mHealth approach. The secondary objectives were to evaluate the barriers, benefits, and willingness to use mHealth services reported by heart transplant recipients and cardiology providers. METHODS: This was an implementation strategy study directed by a multidisciplinary cardiology team conducted in four stages: design of the model and the software, development of the mHeart tool, interoperability among systems, and quality and security requirements. A mixed methods study design was applied combining a literature review, several surveys, interviews, and focus groups. The approach involved merging engineering and behavioral theory science. Participants were chronic-stage heart transplant recipients, patient associations, health providers, stakeholders, and diverse experts from the legal, data protection, and interoperability fields. RESULTS: An interdisciplinary and patient-centered process was applied to obtain a comprehensive care model. The heart transplant recipients (N=135) included in the study confirmed they had access to smartphones (132/135, 97.7%) and were willing to use the mHeart system (132/135, 97.7%). Based on stakeholder agreement (>75%, N=26), the major priorities identified of the mHealth approach were to improve therapy management, patient empowerment, and patient-provider interactions. Stakeholder agreement on the barriers to implementing the system was weak (<75%). Establishing the new model posed several challenges to the multidisciplinary team in charge. The main factors that needed to be overcome were ensuring data confidentiality, reducing workload, minimizing the digital divide, and increasing interoperability. Experts from various fields, scientific societies, and patient associations were essential to meet the quality requirements and the model scalability. CONCLUSIONS: The mHeart model will be applicable in distinct clinical and research contexts, and may inspire other cardiology health providers to create innovative ways to deal with therapeutic complexity and multimorbidity through health care systems. Professionals and patients are willing to use such innovative mHealth programs. The facilitators and key strategies described were needed for success in the implementation of the new holistic theory-based mHealth strategy.

Prevalence and prognostic impact of subclinical pulmonary congestion at discharge in patients with acute heart failure.

AIMS: Residual pulmonary congestion at hospital discharge can worsen the outcomes in patients with heart failure (HF) and can be detected by lung ultrasound (LUS). The aim of this study was to analyse the prevalence of subclinical pulmonary congestion at discharge and its impact on prognosis in patients admitted for acute HF. METHODS AND RESULTS: This is a post-hoc analysis of the LUS-HF trial. LUS was performed by the investigators in eight chest zones with a pocket device. Physical exam was subsequently performed by the treating physicians. Primary outcome was a combined endpoint of rehospitalization, unexpected visit for HF worsening or death at 6- month follow-up. Subclinical pulmonary congestion at discharge was defined as the presence of ≥5 B-lines in LUS in absence of rales in the auscultation employing the area under the ROC curve. At discharge, 100 patients (81%) did not show clinical signs of pulmonary congestion. Of these, 41 had ≥5 B-lines. Independent factors related with the presence of subclinical pulmonary congestion were anaemia, higher New York Heart Association (NYHA) class, and N terminal pro brain natriuretic peptide (NT-proBNP). After adjusting by propensity score analysis including age, renal insufficiency, atrial fibrillation, NYHA class, NT-proBNP levels, clinical congestion, and the trial intervention, the presence of subclinical pulmonary congestion at discharge was a risk factor for the occurrence of the primary outcome (hazard ratio 2.63; 95% confidence interval: 1.08-6.41; P = 0.033). CONCLUSIONS: Up to 40% of patients considered 'dry' according to pulmonary auscultation presents subclinical congestion at hospital discharge that can be detected by LUS and implies a worse prognosis at 6- month follow-up. Comorbidities, high values of natriuretic peptides, and higher NYHA class are the factors related with its presence.

A Mobile App (mHeart) to Detect Medication Nonadherence in the Heart Transplant Population: Validation Study.

BACKGROUND: Medication nonadherence in heart transplant recipients (HTxR) is related to graft loss and death. mHeart is a mobile app that uses electronic patient-reported outcome measures (ePROMs) to identify and manage medication nonadherence in the outpatient heart transplant (HTx) population. OBJECTIVE: The study primarily aimed to validate mHeart to measure medication nonadherence in early stage HTxR by assessing the psychometric properties of ePROMs. The secondary aims were to (1) measure patient satisfaction with the mHeart tool and its usability and (2) explore the impact of a theory-based treatment on medication nonadherence rates to determine its scalability to larger research. METHODS: A prospective study was conducted in the outpatient clinic of a tertiary hospital. All consecutive early stage HTxR (<1.5 years from HTx) were included. The ePROM psychometric properties assessed were validity, reliability, responsiveness, interpretability, and burden. ePROMs comprised the 4-item Morisky-Green-Levine questionnaire and an adapted version of the Haynes-Sackett questionnaire. The Simplified Medication Adherence Questionnaire (SMAQ) was also applied on-site. Three consecutive medication nonadherence assessments were performed by a transplant pharmacist. To improve medication nonadherence, theory-based interventions were delivered in a 1-month period. Patient satisfaction was assessed by a semiquantitative Web-based survey at the end of the study. RESULTS: We included 31 early stage HTxR (age: mean 54 years, SD 12 years), and 71% (22/31) of them were men. The HTxR were taking a mean 13 (SD 4; range 7-18) drugs per day. A total of 42% (13/31) of patients were unaware of the consequences of medication nonadherence, and 39% (12/31) of patients were nonadherent to immunosuppressive treatment. The content validity measure showed excellent levels of expert panel agreement for the Haynes-Sacket (14/14, 100%) and Morisky-Green-Levine (13/14, 93%) questionnaires. SMAQ and Morisky-Green-Levine ePROMs showed similar measurement domains (convergent validity, phi=0.6, P<.001), which, as expected, differed from Haynes-Sackett ePROMs (divergent validity, phi=0.3, P=.12). Reliability assessment revealed a very strong association between ePROM and on-site PROMs (phi>0.7, P<.001). Reproducibility was moderate (Haynes-Sackett κ=0.6, P<.002) or poor (Morisky-Green-Levine κ=0.3, P=.11) because of unexpected improved medication adherence rates during the test-retest period. According to responsiveness, the theory-based multifaceted intervention program improved medication nonadherence by 16% to 26% (P<.05). A burden analysis showed that ePROMs could potentially overcome traditional on-site limitations (eg, automatic recording of ePROM responses in the hospital information system). The mean score for overall patient satisfaction with the mHeart approach was 9 (SD 2; score range: 0-10). All 100% (29/29) of patients surveyed reported that they would recommend the mHeart platform to other HTxR. CONCLUSIONS: ePROMs adhered to the quality standards and successfully identified medication nonadherence in the HTx population, supporting their widespread use. The theory-based intervention program showed a promising improvement in medication adherence rates and produced excellent patient satisfaction and usability scores in HTxR.

Lung ultrasound-guided treatment in ambulatory patients with heart failure: a randomized controlled clinical trial (LUS-HF study).

AIMS: Lung ultrasound (LUS) is a useful tool with which to assess subclinical pulmonary congestion and to stratify the prognosis of patients with heart failure (HF). The aim of this study was to evaluate whether an LUS-guided follow-up protocol improves the outcomes of patients with HF. METHODS AND RESULTS: In this single-blind clinical trial, 123 patients admitted for HF were randomized to either a standard follow-up (n = 62, control group) or a LUS-guided follow-up (n = 61, LUS group). The primary endpoint was a composite of urgent visit, hospitalization for worsening HF and death during follow-up. Visits were scheduled at 14, 30, 90 and 180 days after discharge. Treating physicians were encouraged to modify diuretic therapy in accordance with the number of B-lines recorded by LUS. The mean ± standard deviation (SD) age of the patients was 69 ± 12 years and 72% were male. The mean ± SD left ventricular ejection fraction was 39 ± 14%. The hazard ratio for the primary outcome in the LUS group was 0.518 [95% confidence interval (CI) 0.268-0.998; P = 0.049], mainly resulting from a decrease in the number of urgent visits for worsening HF. The number of patients needed to treat to avoid an event was 5 (95% CI 3-62). Other secondary endpoints such as N-terminal pro-B-type natriuretic peptide reduction were not achieved. The safety parameters were similar in the two groups. Patients in the LUS group received more loop diuretics [51 (91%) vs. 42 (75%); P = 0.02] and showed an improvement in the distance achieved in the 6-min walking test [60 m (interquartile range: 29-125 m) vs. 37 m (interquartile range: 5-70 m); P = 0.023]. CONCLUSIONS: Tailored LUS-guided diuretic treatment of pulmonary congestion in this proof-of-concept study reduced the number of decompensations and improved walking capacity in patients with HF. LUS is a non-invasive, safe and easy-to-use technique with potential clinical applicability to guide pulmonary congestion treatment in patients with HF.

Sacubitril/Valsartan in Real-Life Practice: Experience in Patients with Advanced Heart Failure and Systematic Review.

PURPOSE: Sacubitril/valsartan reduced heart failure (HF) admissions and cardiovascular mortality in the PARADIGM-HF trial. However, real-life studies are scarce comparing daily practice patients with those of the trial. The aim of our study was to analyze the efficacy and safety of the drug in an advanced heart failure cohort and to review systematically the previous real-life studies published to date. METHODS: We performed a retrospective analysis of consecutive patients prescribed sacubitril/valsartan in a single tertiary HF clinic between September 2016 and February 2018. HF admissions before and after the initiation of the drug were assessed in a paired fashion. A systematic review of real-life studies published to date was also conducted. RESULTS: Sacubitril/valsartan was started in 108 patients who were in a more advanced NYHA class and more frequently treated with mineral receptor antagonists, internal cardiac defibrillator, and cardiac resynchronization therapy than in the PARADIGM-HF trial. After a 6-month follow-up, we observed a significant reduction in the HF hospitalizations, median levels of NT-proBNP, and need for levosimendan ambulatory perfusion. Likewise, we found a significant improvement in mean LVEF and end diastolic left ventricle diameter. Regarding safety, sacubitril/valsartan was well-tolerated without any severe adverse effect. CONCLUSION: Sacubitril/valsartan in real-life is prescribed to a more advanced HF population, which could be responsible for the difficulties in reaching high doses of the drug. However, after a 6-month follow-up, sacubitril/valsartan significantly reduces HF hospitalization and induces cardiac reverse remodeling, without remarkable adverse events.

High-Sensitivity Troponin T and Soluble Form of AXL as Long-Term Prognostic Biomarkers after Heart Transplantation.

ANTECEDENTS: Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. AIM: Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. METHODS: 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction < 50%, or heart failure not due to an acute rejection. RESULTS: 51 patients (53%) presented CAV at evaluation; 21 of them had CV events. Hs-cTnT (56 ± 45 versus 20 ± 18 ng/L; p = 0.04) and sAXL concentrations (98 ± 51 versus 26 ± 26 ng/L; p = 0.01) were significantly higher in patients with CV events. Hs-cTnT (HR 1.03; 95% CI 1.015-1.042, p = 0.0001) and sAXL (HR 1.01; 95% CI 1.001-1.019, p = 0.02) were independent predictors of CV events. A hs-cTnT concentration < 21 ng/L, detected by AUC ROC, predicted the absence of CV events with a predictive value of 91%; sAXL did not add more predictive value to hs-cTnT. Survival free of CV events was 92% in patients with hs-cTnT < 21 ng/L and 57% in those with hs-cTnT > 21 ng/L (p < 0.001). CONCLUSION: Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes.

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry.

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women.

CD4+CD45RO+CD25-/lowCD127+: CD4+CD45RO+CD25hiCD127-/low Ratio in Peripheral Blood: A Useful Biomarker to Detect Cardiac Allograft Vasculopathy in Heart Transplanted Patients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major limitation in long-term graft survival after heart transplantation (HTx). Its prediction and detection at an early stage is a challenge because an accurate, minimally invasive blood test is lacking. The aim of this study was to analyze the relationship of Tact (CD4CD45ROCD25-CD127) cells, Th1 cells, and thymus-derived regulatory (Treg) (CD4CD45ROCD25CD127) cells in peripheral blood with the development of CAV in HTx patients. METHODS: First, we performed a cross-sectional study in 29 patients at least 2 years after HTx, 17 with CAV and 12 without CAV. We then prospectively followed a group of 38 patients for 2 years immediately after HTx surgery. In both groups, we analyzed the relationship between CAV and the effector-to-regulatory T cell ratio. RESULTS: In the cross-sectional study, patients with CAV showed statistically significant higher values of Th1-to-FoxP3Treg and Tact-to-CD127Treg ratios than non-CAV patients, with P less than 0.01 and P less than 0.001, respectively. Receiver operating characteristic curve analysis showed that the Tact:CD127Treg ratio was a potential biomarker of CAV, clearly discriminating CAV and non-CAV patients (area under curve [AUC] = 0.955; P = 0.001). In the prospective part of the study, we monitored the Th1:FoxP3Treg and Tact:CD127Treg ratios using the best tradeoff between anterior receiver operating characteristic sensitivity and specificity as a cutoff. Changes in the Tact:CD127Treg ratio were detected earlier than changes in the Th1:FoxP3Treg ratio. Both ratios were higher in HTx patients with CAV. CONCLUSION: The Tact-to-Treg ratio is a valuable follow-up marker to detect HTx patients at risk of developing CAV.

Long-term prognostic value of elevated heart rate one year after heart transplantation.

BACKGROUND: Elevated heart rate (HR) is associated with adverse cardiovascular outcome in the general population and in patients with cardiovascular disease. Elevated HR due to graft denervation is often found in heart transplantation (HTx) patients; the effect on graft survival and vasculopathy is unclear. Thus, the aim of this study was to evaluate the role of elevated HR at 12 months post-HTx and its power to predict HTx long-term outcome. METHODS: We evaluated retrospectively a prospective database of 312 patients undergoing HTx at two centers. HR was registered at 12 months post-HTx. The median HR was used as a cutoff point. Cox regression analysis was performed with variables known to be clinically relevant to mortality and those selected from the univariate analysis. RESULTS: During a mean follow-up of 5.5 ± 2.8 years there were 58 deaths (19%). Patients with a HR ≥ 90 bpm (median HR) at 12 months had an increased risk for all-cause mortality (Hazard Ratio=2.4, 95% CI 1.2 to 4.5, p=0.009) and mortality related to coronary allograft vasculopathy (CAV) (Hazard Ratio=3.0, 95% CI 1.25-7.14, p=0.01). Multivariate analysis showed that a HR ≥ 90 bpm independently predicted mortality (HR 3.2, 95% CI 1.4-7.1, p=0.004). CONCLUSIONS: Elevated HR measured at 12 months after HTx is an independent predictor of all-cause mortality in HTx recipients. A HR ≥ 90 bpm identifies a group of patients at high risk of death and CAV-related mortality at mid- to long-term.

Withdrawal of proliferation signal inhibitors due to adverse events in the maintenance phase of heart transplantation.

BACKGROUND: The increasing use of proliferation signal inhibitors (PSIs) has raised the issue of their risk profile. We sought to determine the causes, incidence, risk factors, and consequences of withdrawal due to adverse events of PSIs in maintenance heart transplantation. METHODS: This was a retrospective study from 9 centers of the Spanish Registry for Heart Transplantation. Demographic, clinical, analytic, and evolution data were obtained for patients in whom a PSI (sirolimus or everolimus) was used between October 2001 and March 2009. RESULTS: In the first year, 16% of 548 patients could not tolerate PSIs. This incidence rate stabilized to 3% to 4% per year thereafter. The most frequent causes for discontinuation were edema (4.7%), gastrointestinal toxicity (3.8%), pneumonitis (3.3%), and hematologic toxicity (2.0%). In multivariate analysis, withdrawal of PSI was related to the absence of statin therapy (p = 0.006), concomitant treatment with anti-metabolites (p = 0.006), a poor baseline renal function (p = 0.026), and multiple indications for PSI use (p = 0.04). Drug discontinuation was associated with a decline in renal function (p = 0.045) but not with an excess in mortality (p = 0.42). CONCLUSIONS: In this large cohort of maintenance heart transplant recipients taking a PSI, 16% withdrew treatment in the first year, and 25% had stopped PSI due to severe adverse events by the fourth year. This high rate of toxicity-related PSI withdrawal could limit the clinical utility of this otherwise novel class of immunosuppressive agents.

Risk factors associated with moderate-to-severe renal dysfunction among heart transplant patients: results from the CAPRI study.

The longer survival of patients with heart transplantation (HT) favors calcineurin inhibitor-related chronic kidney disease (CKD). It behoves to identify risk factors. At 14 Spanish centers, data on 1062 adult patients with HT (age 59.2 ± 12.3 yr, 82.5% men) were collected at routine follow-up examinations. Glomerular filtration rate, GFR, was estimated using the four-variable MDRD equation, and moderate-or-severe renal dysfunction (MSRD) was defined as K/DOQI stage 3 CKD or worse. Time since transplant ranged from one month to 22 yr (mean 6.7 yr). At assessment, 26.6% of patients were diabetic and 63.9% hypertensive; 53.9% were taking cyclosporine and 33.1% tacrolimus; and 61.4% had MSRD. Among patients on cyclosporine or tacrolimus at assessment, multivariate logistic regression identified male sex (OR 0.44), pre- and post-HT creatinine (2.73 and 3.13 per mg/dL), age at transplant (1.06 per yr), time since transplant (1.05 per yr), and tacrolimus (0.65) as independent positive or negative predictors of MSRD. It is concluded that female sex, pre- and one-month post-HT serum creatinine, age at transplant, time since transplant, and immunosuppression with cyclosporine rather than tacrolimus may all be risk factors for development of CKD ≥ stage 3 by patients with HT.

[Acute coronary events among spectators in a soccer stadium]. / Eventos coronarios agudos entre los espectadores de un estadio de fútbol.

The aim of this study was to describe acute coronary syndromes (ACS) with a substantial emotional component in spectators of professional league competition sports events. The study was done at the Barcelona soccer team's home stadium. We recorded cases of ACS that occurred during official competition matches during the 2000-2001 season. A total of 7 episodes of ACS were recorded, 1 involving sudden death, 4 involving acute myocardial infarction and 2 involving angina pectoris. The victim of sudden death had a history of heart disease. The overall risk of ACS was 0.0056 episodes per 100,000 person-hours. We conclude that medical facilities at the stadium facilitated the initial diagnosis of ACS and ensured prompt initial treatment and transport to the reference hospital.

Host cell-derived cardiomyocytes in sex-mismatch cardiac allografts.

BACKGROUND: Mesenchymal precursor cells are able to respond to tissue signals and differentiate into a phenotype characteristic of mature cells of that tissue. We sought to investigate whether adult human cardiomyocytes can be derived from recipient precursor cells in sex-mismatched cardiac allografts. METHODS: We studied four male patients who received hearts from female donors, and four female patients who received an allograft from a male donor. Four sex-matched transplant patients, two of each sex served as controls. Combined fluorescence in situ hybridization with probes specific for X- and Y-chromosomes and immunohistochemistry with alpha-actin was used to identify cardiac muscle cells 4 and 12 months after transplantation. Slides were examined with a fluorescence microscope to detect the presence of male cells with one X and one Y signal in the nucleus, and female cells containing two X signals. RESULTS: Mature cardiomyocytes from the host (1-2%) were found in five endomyocardial biopsy specimens at 4 months, and in three specimens at 12 months. In addition, recipient cells negative for cytoplasmic alpha-actin were also identified (1-21% per slide). The number of infiltrating recipient cells was not associated with the degree of rejection of the sample or with the number of prior rejection episodes. Echocardiographic evaluation showed no improvement in cardiac performance in hearts from patients with more than 10% chimeric recipient cells. CONCLUSIONS: Our data confirm the existence of mature cardiomyocytes derived from host cells, likely mesenchymal precursors, in the adult cardiac allograft in vivo.