Improving access to transcatheter aortic valve implantation across Europe by restructuring cardiovascular services: An expert council consensus statement.

Transcatheter aortic valve implantation (TAVI) is recommended for a growing range of patients with severe aortic stenosis in the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2021 Guidelines update. However, guideline implementation programs are needed to ensure the application of clinical recommendations which will favorably influence disease outcomes. An Expert Council was convened to identify whether cardiology services across Europe are set up to address the growing needs of patients with severe aortic stenosis for increased access to TAVI by identifying the key challenges faced in growing TAVI programs and mapping associated solutions. Wide variation exists across Europe in terms of TAVI availability and capacity to deliver the increased demand for TAVI in different countries. The recommendations of this Expert Council focus on the short-to-medium-term aspects where the most immediate, actionable impact can be achieved. The focus on improving procedural efficiency and optimizing the patient pathway via clinical practice and patient management demonstrates how to mitigate the current major issues of shortfall in catheterization laboratory, workforce, and bed capacity. Procedural efficiencies may be achieved through steps including streamlined patient assessment, the benchmarking of standards for minimalist procedures, standardized approaches around patient monitoring and conduction issues, and the implementation of nurse specialists and dedicated TAVI coordinators to manage organization, logistics, and early mobilization. Increased collaboration with wider stakeholders within institutions will support successful TAVI uptake and improve patient and economic outcomes. Further, increased education, collaboration, and partnership between cardiology centers will facilitate sharing of expertise and best clinical practice.

Aspirin use and bleeding events during thrombocytopenia after autologous stem-cell transplantation for multiple myeloma.

Background: In patients with cardiovascular (CV) comorbidities that necessitate antiplatelet therapy (APT), its optimal management during chemotherapy-induced thrombocytopenia remains elusive, as the risk of bleeding has to be balanced against the risk of CV events. The purpose of this study was to assess the risk for bleeding with APT during thrombocytopenia in patients with multiple myeloma undergoing high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT) with and without acetylsalicylic acid (ASA) as comedication. Methods: We assessed patients who underwent ASCT at the Heidelberg University Hospital between 2011 and 2020 for bleeding events, management strategies for ASA intake during thrombocytopenia, transfusion requirements, and the occurrence of CV events. Results: There were 57/1,113 patients who continued ASA until at least 1 day after ASCT; thus, a continuous platelet inhibition during thrombocytopenia was assumed. Most of the patients (41/57) continued ASA until they had a platelet count of 20-50/nl. This range reflects the kinetics of thrombocytopenia and nondaily measurements of platelets during ASCT. A tendency toward a higher risk for bleeding events in the ASA group was demonstrated (1.9% (control group) vs. 5.3% (ASA), p = 0.082). The risk factors for bleeding in multivariate analysis were the duration of thrombocytopenia < 50/nl, a history of gastrointestinal bleeding, and diarrhea. The factors predicting the duration of thrombocytopenia were age >60 years, a hematopoietic stem-cell transplantation comorbidity index ≥3, and an impaired bone marrow reserve at admission. CV events occurred in three patients; none of them took ASA or had an indication for APT. Conclusions: The intake of ASA until thrombocytopenia with a platelet count of 20-50/nl appears safe, although an elevated risk cannot be excluded. If ASA is indicated for the secondary prevention of CV events, the evaluation of risk factors for bleeding and a prolonged time of thrombocytopenia before conditioning is crucial to adapt the strategy for ASA intake during thrombocytopenia.

Prognostic relevance of gradual weight changes on long-term mortality in chronic heart failure.

BACKGROUND AND AIMS: While obesity has been linked to better ouctomes (the obesity paradox), cachexia is associated with higher mortality in patients with heart failure with reduced ejection fraction (HFrEF). As opposed to overt cachexia, little is known about the prognostic impact of gradual, long-term weight changes in stable HFrEF. METHODS AND RESULTS: We included ambulatory patients with clinically stable chronic HFrEF on individually optimized treatment. Next to other clinical and functional parameters, changes in body weight over the past one (n = 733, group 1) or two (n = 636, group 2) years were recorded. Four-year mortality was analysed with respect to baseline BMI and changes in body weight or BMI using fractional polynomials. In addition, outcome was stratified by BMI categories (18.5-25 kg/m2: normal weight, >25-30 kg/m2: overweight, >30 kg/m2: obesity). An obesity paradox was present in both groups, with overweight and obese patients having the best prognosis. In both groups, a gradual weight gain of 5% was associated with the lowest mortality, whereas mortality steadily increases with increasing weight loss. Excessive weight gain >10% was also related to higher mortality. Stratification by baseline BMI categories revealed that weight loss was most detrimental in normal weight patients, whereas the prognostic impact of weight change was weaker in obese patients. CONCLUSION: In patients with chronic HFrEF, gradual weight loss is associated with steadily increasing mortality, whereas a weight gain of 5% is related to the best prognosis. Prevention of any inappropriate weight loss might be a therapeutic goal in HFrEF patient care.

Impact of the introduction of percutaneous edge-to-edge mitral valve reconstruction on clinical practice in Germany compared to surgical valve repair.

BACKGROUND: The introduction of percutaneous mitral valve (MV) repair had an effect on clinical practice in comparison with surgical MV repair. Complete nationwide data are useful in examining how the introduction of a new technique influences clinical practice. METHODS: We analyzed procedural numbers, patient characteristics, and in-hospital outcomes for all percutaneous edge-to-edge and surgical MV reconstruction procedures performed in Germany between 2009 and 2015. RESULTS: 12,664 percutaneous edge-to-edge and 22,825 surgical MV reconstructions were recorded. Numbers increased steadily, albeit more rapidly in the percutaneous edge-to-edge group (108-4079 vs. 2923-3603 with surgical MV reconstruction). Patients with percutaneous edge-to-edge MV reconstruction were older (75.6 ± 8.8 vs 61.6 ± 13.4 years, P < 0.001) and at higher operative risk (estimated logistic EuroSCORE 13.2% vs. 4.7%, P < 0.001) compared to those undergoing surgery. However, in-hospital mortality did not differ (2.9% vs. 2.8%; P = 0.395). This was also true for the subset of 2103 patients at intermediate operative risk as defined by a logistic EuroSCORE ≥ 4% and ≤ 9%. Of note, complication rates (except acute kidney injury) were more favorable in patients undergoing percutaneous edge-to-edge reconstruction. CONCLUSIONS: Percutaneous edge-to-edge MV reconstruction has markedly changed clinical practice of MR therapy in Germany. Annual overall procedural numbers more than doubled, with a massive increase in percutaneous edge-to-edge procedures. Our data demonstrate its use mainly in high-risk patients and prove the favorable safety profile of this novel technique, with low in-hospital mortality and complication rates.

An analysis of the cost-effectiveness of transcatheter mitral valve repair for people with secondary mitral valve regurgitation in the UK.

BACKGROUND AND AIMS: A proportion of chronic heart failure (CHF) patients will experience regurgitation secondary to ventricular remodeling in CHF, known as functional mitral (MR) or tricuspid (TR) regurgitation. Its presence adversely impacts the prognosis and healthcare utilization in CHF patients. The advent of interventional devices for both atrioventricular valves modifies both aspects. We present an economic model structure suitable for comparing interventions used in MR and TR, and assess the cost-effectiveness of transcatheter mitral valve repair (TMVr) plus guideline directed medical therapy (GDMT) compared with GDMT alone in people with MR. METHODS: An economic model with a lifetime time horizon was developed based on extrapolated survival data and using New York Heart Association classifications to describe disease severity in people with functional MR at high risk of surgical mortality or deemed inoperable. Cost and utility values (describing health-related quality-of-life) were assigned to patients dependent on their disease severity. The analysis was conducted from a UK National Health Service perspective. An incremental cost per additional quality-adjusted life year (QALY) was estimated, and sensitivity (one-way and probabilistic) and scenario analyses conducted. RESULTS AND CONCLUSIONS: Compared with GDMT, the use of TMVr results in an additional 1.07 QALYs and an increase in costs of £32,267 per patient over a lifetime time horizon. The estimated incremental cost per QALY gained is £30,057 and would therefore be on the threshold of cost-effectiveness at £30,000 per quality adjusted life year. Thus, from a UK reimbursement perspective, in patients with severe functional MR who are at high risk of surgical mortality or deemed inoperable with conventional surgery, TMVr plus medical therapy is likely to represent a cost-effective treatment option compared with GDMT alone. The choice of device (MitraClip or PASCAL) will need to be confirmed once further clinical data are reported.

Relative Efficacy of Spironolactone, Eplerenone, and cAnRenone in patients with Chronic Heart failure (RESEARCH): a systematic review and network meta-analysis of randomized controlled trials.

This study aims to assess the comparative benefit and risk profile of treatment with mineralocorticoid receptor antagonists (MRAs) with regard to all-cause mortality (primary endpoint), cardiovascular mortality, or heart failure (HF)-related hospitalization (secondary endpoints) and the safety endpoints hyperkalemia, acute renal failure, and gynecomastia in patients with chronic HF. We conducted a systematic review and network meta-analysis following PRISMA-P and PRISMA-NMA guidelines. From 16 different sources, 14 randomized controlled trials totaling 12,213 patients testing an active treatment of either spironolactone, eplerenone, or canrenone/potassium-canreonate in adults with symptomatic HF due to systolic dysfunction reporting any of the above endpoints were retained. Efficacy in comparison to placebo/standard medical care with respect to all-cause mortality was confirmed for spironolactone and eplerenone while no conclusion could be drawn for canrenone (HR 0.69 (0.62; 0.77), 0.82 (0.75; 0.91), and 0.50 (0.17; 1.45), respectively). Indirect comparisons hint a potential (non-significant) preference of spironolactone over eplerenone (HR 0.84 (0.68; 1.03)). The overall risk of bias was low to intermediate. Results for secondary endpoints as well as sensitivity analyses essentially mirrored these findings. The beta-blocker adjusted meta-analysis for the primary endpoint showed the same tendency as the unadjusted one (HR 0.39 (0.07; 2.03)). Results need to be interpreted with caution, though, as the resultant mix of patient- and study-level covariates produced unstable statistical modeling. We found no significant and systematic superiority of either MRA regarding efficacy toward all endpoints considered in both direct and indirect comparisons.

The chameleon of cardiology: cardiac sarcoidosis before and after heart transplantation.

Cardiac sarcoidosis is a chronic inflammatory disease with a large spectrum of symptoms that can mimic diseases such as dilated, hypertrophic, or arrhythmogenic cardiomyopathies. It can be asymptomatic but can also present with ventricular arrhythmias, conduction disease, and heart failure (HF) or even sudden cardiac death (SCD). We present here the case of a patient transplanted due to end-stage arrhythmogenic right ventricular cardiomyopathy (ARVC), fulfilling the task force criteria. A few years after successful heart transplantation (HTX), the patient developed similar symptoms and morphofunctional changes of the heart, which led to critical re-evaluation of his primary diagnosis.

Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis.

BACKGROUND: Angiotensin peptides have been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. Angiotensin modulators are used to treat arterial hypertension, a frequent comorbidity of IPF. This post hoc analysis evaluated associations of antihypertensive treatments with disease-related outcomes in IPF. METHODS: All patients randomized to placebo (n = 624) in the CAPACITY and ASCEND studies were categorized by antihypertensive treatment at baseline. Outcomes of disease progression (first occurrence of ≥ 10% absolute decline in % predicted FVC, ≥ 50-m decline in 6-min walk distance, or death) and all-cause mortality were assessed over 52 weeks. RESULTS: At baseline, 111 and 121 patients were receiving an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), respectively; 392 were receiving neither. In multivariable analyses adjusted for differences in baseline characteristics compared with the non-ACEi/ARB group, ACEi treatment (hazard ratio [HR], 0.6 [95% CI, 0.4-0.9]; P = .026), but not ARB (HR, 0.9 [95% CI, 0.6-1.2]; P = .413), was associated with slower disease progression. Furthermore, the increase in all-cause mortality associated with cardiovascular disease was not observed in the ACEi group (HR, 1.1 [95% CI, 0.5-2.9]; P = .782), which presented a similar percentage of IPF-related mortality as the non-ACEi/ARB group (3.6% vs 3.6%). In contrast, patients in the ARB group had greater risk of all-cause mortality (HR, 2.5 [95% CI, 1.2-5.2]). These observations were validated in a pooled analysis that included patients from the INSPIRE trial. CONCLUSIONS: Prospective clinical trials are needed to evaluate whether angiotensin modulators may be beneficial to clinical outcomes in IPF. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT01366209, NCT00287716, NCT00287729, NCT00075998; URL: www.clinicaltrials.gov).

The need for dedicated advanced heart failure units to optimize heart failure care: impact of optimized advanced heart failure unit care on heart transplant outcome in high-risk patients.

AIM: With an increasing prevalence of heart failure (HF), more patients with advanced disease have to be treated in cardiology units by sophisticated medical and interventional strategies. We therefore developed a dedicated advanced heart failure unit (AHFU) to target the specific needs of the many patients with advanced HF. We here present our concept and its impact on outcome in high-risk high-urgency (HU) heart transplant candidates. METHODS AND RESULTS: The eight-bed unit was established as an extension of the cardiologic intensive care and coronary care units in an intermediate care setting. Each bed was equipped with 24 h haemodynamic, respiratory, and arrhythmia monitoring. The unit is served 24/7 by five residents in cardiology, one staff cardiologist specializing in medical and interventional HF care, and 10 intensive care nurses. The cardiology team is supported by colleagues from cardiac surgery, sports medicine, psychosomatics, and the internal medicine departments. As an example of the intensified care on the AHFU, data from the cohorts of patients undergoing heart transplantation from HU status before (pre-AHFU 2008-11) and after establishment of the AHFU (AHFU 2012-15) were analysed. Interestingly, mortality on HU waiting list and post-heart transplant survival was comparable in both cohorts, despite significant increase in morbidity and co-morbidity as assessed by the Index for Mortality Prediction After Cardiac Transplantation model in the AHFU group. CONCLUSIONS: Our AHFU provides a unique and novel setting for the integration of modern pharmacological, interventional, surgical, and supportive HF therapy embedded in an academic heart centre. This may be a major step forward in the care of critical patients with advanced HF.

Improved outcomes after heart transplantation for cardiac amyloidosis in the modern era.

BACKGROUND: Cardiac amyloidosis, caused most commonly by deposition of light chain (AL) or transthyretin (ATTR) type fibrils, has an extremely poor prognosis. In this retrospective single-center study, we evaluated temporal trends in survival after heart transplantation for cardiac amyloidosis. METHODS: We analyzed 48 patients with cardiac amyloidosis (AL, n = 32; familial ATTR, n = 16) who underwent heart transplantation from May 2002 to March 2017. Patients were analysed in 2 periods, Era 1 (2002- 2007) and Era 2 (2008- 2017), separated by altered patient selection in both, AL and ATTR amyloidosis, and changed chemotherapy regimens for AL amyloidosis. RESULTS: The modern era was characterized by a lower number of extracardiac organ involvement for AL (94% isolated cardiac amyloidosis in Era 2 vs 56% in Era 1; p = 0.0221), and more frequent treatment for AL with the proteasome inhibitor bortezomib (94% in Era 2 vs 6% in Era 1; p < 0.0001). AL patients had significantly lower survival than patients with non-amyloid cardiomyopathy after heart transplantation in Era 1, and ATTR patients had numerically lower survival. However, survival in the modern era was comparable to non-amyloid transplants in both cohorts, possibly reflecting a shift in chemotherapy strategies and patient selection, respectively. CONCLUSIONS: In the current era, use of enhanced chemotherapy regimens for isolated advanced AL cardiac amyloidosis was associated with outcomes comparable to non-amyloid cardiomyopathy. We conclude that heart transplantation in highly selected patients with isolated non-systemic advanced cardiac amyloidosis may be a feasible approach.

Transcatheter Aortic Valve Replacement: The New Standard in Patients With Previous Coronary Bypass Grafting?

OBJECTIVES: The aim of this study was to assess how the introduction of transcatheter aortic valve replacement (TAVR) has changed clinical practice and outcome in patients who have previously undergone coronary artery bypass grafting (CABG). BACKGROUND: A significant proportion of patients admitted for aortic valve replacement have previously undergone CABG and are therefore at increased operative risk in case of redo surgery. METHODS: In-hospital outcome data were analyzed from patients with or without previous CABG undergoing isolated surgical aortic valve replacement or TAVR in Germany from 2007 to 2013. RESULTS: In total, 32,581 TAVR and 55,992 surgical aortic valve replacement procedures were performed in patients with (n = 6,221) or without (n = 82,352) previous CABG. TAVR increased markedly in patients with previous CABG, from 18 procedures in 2007 to 1,191 in 2013, while surgical aortic valve replacement decreased in these patients from 471 to 179 procedures. In 2013, TAVR was the preferred therapy in almost 90% of patients with previous CABG. In-hospital mortality was increased in patients with previous CABG compared with those without (7.6% vs. 6.3% for TAVR and 7.2% vs. 2.6% for surgical aortic valve replacement). Bleeding and stroke rates were also increased with redo surgical aortic valve replacement procedures (with vs. without previous CABG: stroke, 3.2% vs. 1.8%; relevant bleeding, 29.6% vs. 13.4%; acute kidney injury, 4.2% vs. 2.9%), whereas this was not the case with TAVR (stroke, 2.1% vs. 2.6%; relevant bleeding, 7.3% vs. 8.3%; acute kidney injury, 6.3% vs. 5.4% respectively). A similar influence was seen in resource utilization (discharge destination home: TAVR after CABG, 51%; surgical aortic valve replacement after CABG, 31%). CONCLUSIONS: Since its introduction in 2007, TAVR has been increasingly used in Germany in patients with previous CABG, and in-hospital outcome data support the trend away from redo surgery.

Analysis of malignancies in patients after heart transplantation with subsequent immunosuppressive therapy.

OBJECTIVE: The aim of this study was to analyze the distribution of malignancies in patients after heart transplantation (HTX) and to evaluate the risk factors including immunosuppressive therapy with regard to the development of malignancies and survival. Special emphasis was placed on the effects of a mammalian target of rapamycin (mTOR) containing immunosuppressive regimen. METHODS: A total of 381 patients (age ≥18 years) receiving HTX were included in the present analysis. All patients were followed-up at the University of Heidelberg Heart Center, Heidelberg, Germany. Data were retrieved from the Heidelberg Registry for Heart Transplantation being collected between 1989 and 2014. According to center standard, all patients received induction therapy with anti-thymocyte globulin guided by T-cell monitoring since 1994. The initial immunosuppressive regimen consisting of cyclosporine A (CsA) and azathioprine (AZA) was replaced by CsA and mycophenolate mofetil (MMF) in 2001 and by tacrolimus (TAC) and MMF in 2006. Additionally, mTOR inhibitors (everolimus/sirolimus) were applied since 2003. RESULTS: Mean recipient age at HTX was 51.2±10.5 years and the mean follow-up period after HTX was 9.7±5.9 years. During follow-up, 130 patients developed a neoplasm (34.1% of total). Subgroup analysis revealed 58 patients with cutaneous malignancy only (15.2%), 56 patients with noncutaneous malignancy only (14.7%), and 16 patients with both cutaneous and noncutaneous malignancy (4.2%). Statistically significant risk factors associated with an increased risk of malignancy after HTX were older age (P<0.0001), male recipients (P=0.0008), dyslipidemia (P=0.0263), diabetes mellitus (P=0.0003), renal insufficiency (P=0.0247), and >1 treated rejection episode (TRE) in the first year after HTX (P=0.0091). Administration of CsA (P=0.0195), AZA (P=0.0008), or steroids (P=0.0018) for >1 year after HTX was associated with increased development of malignancy, whereas administration of MMF (P<0.0001) or mTOR inhibitors (P<0.0001) was associated with a lower risk for development of malignancy. Additionally, 5-year follow-up of cutaneous malignancy recurrence (P=0.0065) and noncutaneous malignancy mortality (P=0.0011) was significantly lower in patients receiving an mTOR inhibitor containing therapy after the development of a malignancy. CONCLUSION: This study highlights the complexity of risk factors including immunosuppression with regard to the development of malignancies after HTX. mTOR-inhibitor-based immunosuppression is associated with a better outcome after HTX, particularly in cases with noncutaneous malignancy.

Biological variation of the cardiac index in patients with stable chronic heart failure: inert gas rebreathing compared with impedance cardiography.

AIMS: In chronic heart failure (CHF), changes in cardiac function define the course of the disease. The cardiac index (CI) is the most adequate indicator of cardiac function. Interpretation of serial CI measurements, however, requires knowledge of the biological variation of CI. Because measurements of CI can be confounded by the clinical situation or the method applied, biological variation might be subject to the same confounders. METHODS AND RESULTS: We prospectively included 50 CHF patients who met rigid criteria for clinical stability. CI was measured by both inert gas rebreathing (IGR) and impedance cardiography (ICG) in weekly intervals over 3 weeks-each measurement performed at rest (IGRrest/ICGrest) and during low-exercise 10 Watt pedalling (IGR10W/ICG10W). Intra-class correlation coefficients (ICCs), reference change values, and minimal important differences of CI were determined for IGRrest, ICGrest, IGR10W, and ICG10W. Impedance cardiography and IGR showed moderate agreement at rest (20% (6-36)) and good agreement at 10 Watt (-4% (-23-16)). Depending on time interval, measurement modality for CI, and mode, ICC ranged between 0.42 and 0.78, ICC values for IGR were lower than those for ICG. Reference change value ranged between 3 and 15%, and minimal important difference ranged between 0.2 and 0.5 L/min/m2. Values for IGR were lower at rest and higher at 10 Watt than those for ICG. CONCLUSION: Non-invasive measurements of CI are stable over time. Measurement modalities for CI, however, are not interchangeable. Biological variation is less pronounced when obtained by ICG. The influence of low-level exercise on stability of CI depends on the measurement modality.

Potentially modifiable correlates of functional status in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) patients suffer from multiple and agonizing symptoms like shortness of breath and reduced functional status, the latter of which is usually assessed using New York Heart Association (NYHA) functional class. PURPOSE: In order to identify potentially modifiable factors of reduced functional status in patients with CHF, we investigated somatic and psychosocial correlates of NYHA functional class. We subsequently compared the results to correlates of left ventricular ejection fraction (LVEF) as an objective parameter of disease severity. METHODS: The cross-sectional study (n = 314) was part of the German Heart Failure Network. Data were analysed using a logistic regression modelling process. RESULTS: In the final regression model, NYHA functional class was only significantly associated with depression (odds ratio (OR) = 1.18; 95% confidence interval (CI) = 1.09-1.27) and multimorbidity (OR = 1.17; 95% CI = 1.04-1.32). LVEF was associated with amino-terminal pro-brain natriuretic peptide (NT-proBNP) (OR = 0.60; 95% CI = 0.44-0.82), aetiology of CHF (OR = 2.08; 95% CI = 1.11-3.90), and smoking (OR = 2.21; 95% CI = 1.25-3.91). CONCLUSIONS: Whereas LVEF was not related to depression, our data revealed a close association between functional status (as assessed by NYHA functional class) and depression in patients with CHF, even after adjusting for cardiac and socio-demographic variables. Different forms of underlying causal mechanisms could be suspected; it appears promising to further investigate this specific interaction. In any event, pending further investigation, our results underscore the need to examine CHF patients with respect to both somatic symptom burden and potential depressive disorders.

Clinical characteristics, morbidity, and prognostic value of concomitant coronary artery disease in idiopathic dilated cardiomyopathy.

BACKGROUND: Patients with idiopathic dilated cardiomyopathy (dCMP) might present coronary artery disease (CAD) concomitant to dCMP and prognostic differences between ischemic heart disease and non-ischemic cardiomyopathy have been described. Clinical characteristics and prognostic implications of concomitant CAD in patients with dCMP are largely unknown. METHODS: A total of 1,263 patients with chronic systolic dysfunction from dCMP-of these 67.1 % (n = 847; 72.3 % men) without and 32.9 % (n = 416; 80.8 % men) with concomitant CAD were included and baseline clinical characteristics noted. They were followed prospectively for 36.3 (20.8-65.0) months, representing 5,168 patient-years. All-cause mortality was the primary endpoint; and decompensation requiring hospitalisation as well as the combined endpoint thereof were secondary endpoints. RESULTS: Independent significant predictors of CAD were smoking status (current smoker: OR 2.68, 95 % CI 1.61-4.46; p < 0.001; past smoker: OR 2.52, 95 % CI 1.40-4.52; p < 0.005; each vs. non-smoker), presence of dyslipidemia (OR 3.46, 95 % CI 2.23-5.35; p < 0.001), age (OR 1.06, 95 % CI 1.04-1.08; p < 0.001), and female sex (OR 0.49, 95 % CI 0.29-0.81; p = 0.005). The presence of CAD was not a significant predictor of all-cause mortality (adjusted HR 0.74, 95 % CI 0.36-1.54; p = 0.42), morbidity (adjusted HR 1.48, 95 % CI 0.55-3.99; p = 0.44), or the combined endpoint (HR 0.65, 95 % CI 0.24-1.78; p = 0.40). CONCLUSION: Concomitant CAD is common in patients with dCMP. Clinical predictors of its presence are largely coincident with classic risk factors in the general population. The presence of concomitant CAD appears not to be associated with adverse prognosis (morbidity or mortality) in patients with dCMP.

Epstein-Barr virus load in whole blood is associated with immunosuppression, but not with post-transplant lymphoproliferative disease in stable adult heart transplant patients.

Development of Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real-time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty-seven patients (39.0% of total) had a positive EBV PCR at initial examination [median 4.9 (range 1.1-16.9) years post-HTX]. In follow-up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 +/- 70.2 vs. 119.6 +/- 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated.