Impact of Atrial Fibrillation on the Symptoms and Echocardiographic Evaluation of Patients With Aortic Stenosis.

Atrial fibrillation (AF) is common in patients with aortic stenosis (AS) and complicates the assessment of AS severity. The overlapping of symptoms in these 2 conditions may postpone valve replacement. This study aimed to evaluate the effect of AF on the severity assessment of AS and its impact on symptoms and quality of life (QoL). Patients with severe AS were prospectively recruited. Echocardiography, symptom questionnaires, and RAND-36 QoL assessment were performed preoperatively and 3 months postoperatively. The aortic valve calcium score (AVC) was measured using computed tomography. Of the 279 patients, 74 (26.5%) had AF. Patients with AF had lower mean gradients and 45.9% had a low-gradient phenotype, with a mean gradient <40 mm Hg, compared with 22.4% of those without AF (p <0.001). The AVC measurements revealed severe valve calcification equally in patients with or without AF (85.7% vs 87.7%, p = 0.78). Patients with AF were more symptomatic at baseline, with 50.0% versus 27.3% in New York Heart Association class III or higher (p <0.001), and after intervention. Patients with AF had more residual dyspnea (27.3% vs 12.0%, p = 0.007) and exercise intolerance (36.4% vs 17.0%, p = 0.002). The QoL improved significantly in both groups but was worse at baseline in patients with AF and remained impaired after intervention. In conclusion, low-gradient AS phenotype is overrepresented in patients with AF, but they have equally severe stenosis determined using AVC, despite the lower gradients. Patients with AF have more symptoms and worse QoL, but they improve significantly after intervention. In patients with AF, multimodality imaging is important in the assessment of AS severity.

Amiodarone accumulates two cholesterol precursors in myocardium: A controlled clinical study.

BACKGROUND: Amiodarone is an effective antiarrhythmic drug, which interferes with cholesterol synthesis. In the human body, it inhibits two enzymes in the cholesterol-synthesis pathway, followed by increases especially in serum desmosterol and zymostenol concentrations and a decrease in that of serum lathosterol. OBJECTIVES: We explored whether desmosterol and zymostenol accumulate also in myocardial tissue during amiodarone treatment. METHODS: Thirty-three patients admitted for cardiac transplantation volunteered for the study. Ten patients were on amiodarone treatment (AD group) and 23 were not (control group). The groups were matched as regards demographic and clinical variables. Myocardial samples were obtained from the removed hearts from 31 patients. Cholesterol, non-cholesterol sterols and squalene were quantified by means of gas-liquid chromatography. RESULTS: In serum and myocardium, desmosterol was 19- and 18-fold higher and zymostenol 4- and 2-fold higher in the AD group versus the control group (p < 0.001 for all). In contrast, myocardial cholesterol, squalene and lathosterol levels were lower in the AD group than in the control group (p < 0.05 for all). Levels of phytosterols and cholestanol were similar in the serum and myocardium in the two groups. Levels of myocardial and serum desmosterol, zymostenol, lathosterol and phytosterols correlated with each other in both groups (p < 0.05 for all). CONCLUSION: Amiodarone treatment caused the accumulation of desmosterol and zymostenol in myocardium. In particular, myocardial desmosterol concentrations were substantially elevated, which may play a part in some of the therapeutic and adverse effects of amiodarone treatment.

Outcomes after coronary artery bypass grafting and percutaneous coronary intervention in diabetic and non-diabetic patients.

AIMS: To assess the prognosis of patients with coronary heart disease (CHD) after first myocardial revascularisation procedure in real-world practice and to compare the differences in outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) among diabetic and non-diabetic patients. METHODS AND RESULTS: A database was compiled from the national hospital discharge register to collect data on all cardiac revascularisations performed in Finland in 2000-2015. The outcomes (all-cause deaths, cardiovascular (CV) deaths, major CV events and need for repeat revascularisation) after the first revascularisation were identified from the national registers at 28 day, 1 year, and 3 year time points.A total of 139 242 first-time revascularisations (89 493 PCI and 49 749 CABG) were performed during the study period. Of all the revascularised patients, 24% had diabetes, and 76% were non-diabetic patients. At day 28, the risk of fatal outcomes was lower after PCI than after CABG among non-diabetic patients, whereas no difference was seen among diabetic patients. In long-term follow-up the situation was reversed with PCI showing higher risk compared with CABG for most of the outcomes. In particular, at 3 year follow-up the risk of all-cause deaths was elevated among diabetic patients [HR 1.30 (95% CI 1.22-1.38) comparing PCI with CABG] more than among non-diabetic patients [HR 1.09 (1.04-1.15)]. The same was true for CV deaths [HR 1.29 (1.20-1.38) among diabetic patients, and HR 1.03 (0.98-1.08) among non-diabetic patients]. CONCLUSION: Although PCI was associated with better 28 day prognosis, CABG seemed to produce better long-term prognosis especially among diabetic patients.

Peak flow measurements in patients with severe aortic stenosis: a prospective comparative study between cardiovascular magnetic resonance 2D and 4D flow and transthoracic echocardiography.

BACKGROUND: Aortic valve stenosis (AS) is the most prevalent valvular disease in the developed countries. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is an emerging imaging technique, which has been suggested to improve the evaluation of AS severity compared to two-dimensional (2D) flow and transthoracic echocardiography (TTE). We investigated the reliability of CMR 2D flow and 4D flow techniques in measuring aortic transvalvular peak systolic flow in patients with severe AS. METHODS: We prospectively recruited 90 patients referred for aortic valve replacement due to severe AS (73.3 ± 11.3 years, aortic valve area 0.7 ± 0.1 cm2, and 54/36 tricuspid/bicuspid), and 10 non-valvular disease controls. All the patients underwent echocardiography and 2D flow and 4D flow CMR. Peak flow velocity measurements were compared using Wilcoxon signed rank sum test and Bland-Altman analysis. RESULTS: 4D flow underestimated peak flow velocity in the AS group when compared with TTE (bias - 1.1 m/s, limits of agreement ± 1.4 m/s) and 2D flow (bias - 1.2 m/s, limits of agreement ± 1.6 m/s). The differences between values obtained by TTE (median 4.3 m/s, range 2.7-6.1 m/s) and 2D flow (median 4.5 m/s, range 2.9-6.5 m/s) compared to 4D flow (median 3.1 m/s, range 1.7-5.1 m/s) were significant (p < 0.001). The difference between 2D flow and TTE were insignificant (bias 0.07 m/s, limits of agreement ± 1.5 m/s). In non-valvular disease controls, peak flow velocity was measured higher by 4D flow than 2D flow (1.4 m/s, 1.1-1.7 m/s and 1.3 m/s, 1.1-1.5 m/s, respectively; bias 0.2 m/s, limits of agreement ± 0.16 m/s). CONCLUSIONS: CMR 4D flow significantly underestimates systolic peak flow velocity in patients with severe AS. 2D flow, in turn, estimated the AS velocity accurately, with measured peak flow velocities comparable to TTE.

Clinical practice patterns in revascularization of diabetic patients with coronary heart disease: nationwide register study.

Aims: To compare diabetic patients with coronary heart disease (CHD) needing revascularization to corresponding non-diabetic patients in terms of revascularization methods, comorbidities and urgency of procedure. We also examined the impact of patient characteristics and comorbidities on the revascularization method.Methods: We identified all diabetic (n = 33,018) and non-diabetic (n = 106,224) patients with first-ever, percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) from electronic health records in Finland between 2000 and 2015.Results: Overall, PCI was the most common revascularization method. PCI outnumbered CABG in women and men both in diabetic and non-diabetic patients. However, diabetic patients were more likely to undergo CABG than PCI (OR 1.30; 95% CI 1.27-1.34, adjusted for age, gender, region of residence and procedure year). Moreover, 26.9% of diabetic patients' urgent procedures were CABG compared to 21.6% in non-diabetic patients (p<.001). Among diabetic patients, prior myocardial infarction was associated with increased odds of CABG, whereas female gender, atrial fibrillation, congestive heart failure, hypertension and later procedure year were associated with lower odds of CABG.Conclusions: CABG has been performed more frequently in diabetic than in non-diabetic CHD patients. Nevertheless, PCI was the dominant revascularization method over CABG both in diabetic and non-diabetic patients. KEY MESSAGESPCI was the dominant revascularization method in both diabetic and non-diabetic patients. Diabetic patients were more likely to undergo CABG than PCI when compared to non-diabetic patients (OR: 1.30; CI 1.27-1.34).Diabetic patients underwent urgent CABG procedures more often than non-diabetic patients and had more comorbidities compared to non-diabetic patients.

Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients: Design of the randomized controlled EVOLVD trial.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is characterized by diffuse thickening of the arterial intima. Statins reduce the incidence of CAV, but despite the use of statins, CAV remains one of the leading causes of long-term death after heart transplant. Inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) substantially reduce cholesterol levels but have not been tested in heart transplant recipients. METHODS: The Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients (EVOLVD) trial (ClinicalTrials.gov Identifier: NCT03734211) is a randomized, double-blind trial designed to test the effect of the PCSK9 inhibitor evolocumab on coronary intima thickness in heart transplant recipients. Adults who have received a cardiac transplant within the past 4-8 weeks are eligible. Exclusion criteria include an estimated glomerular filtration rate < 20 mL/min/1.73 m2 , renal replacement therapy, or contraindications to coronary angiography with intravascular ultrasound. 130 patients will be randomized (1:1) to 12-month treatment with evolocumab or matching placebo. The primary endpoint is the coronary artery intima thickness as measured by intravascular ultrasound. CONCLUSION: The EVOLVD trial is a randomized clinical trial designed to show whether treatment with the PCSK9 inhibitor evolocumab can ameliorate CAV over the first year after heart transplant.

Acute coronary syndromes and acute heart failure: a diagnostic dilemma and high-risk combination. A statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology.

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients.

Cost-utility of venoarterial extracorporeal membrane oxygenation in cardiogenic shock and cardiac arrest.

BACKGROUND: The use of venoarterial extracorporeal membrane oxygenation in cardiogenic shock keeps increasing, but its cost-utility is unknown. METHODS: We studied retrospectively the cost-utility of venoarterial extracorporeal membrane oxygenation in a five-year cohort of consequent patients treated due to refractory cardiogenic shock or cardiac arrest in a transplant centre in 2013-2017. In our centre, venoarterial extracorporeal membrane oxygenation is considered for all cardiogenic shock patients potentially eligible for heart transplantation, and for selected postcardiotomy patients. We assessed the costs of the index hospitalization and of the one-year hospital costs, and the patients' health-related quality of life (response rate 71.7%). Based on the data and the population-based life expectancies, we calculated the amount and the costs of quality-adjusted life years gained both without discount and with an annual discount of 3.5%. RESULTS: The cohort included 102 patients (78 cardiogenic shock; 24 cardiac arrest) of whom 67 (65.7%) survived to discharge and 66 (64.7%) to one year. The effective costs per one hospital survivor were 242,303€. Median in-hospital costs of the index hospitalization per patient were 129,967€ (interquartile range 150,340€). Mean predicted number of quality-adjusted life years gained by the treatment was 20.9 (standard deviation 9.7) without discount, and the median cost per quality-adjusted life year was 7474€ (interquartile range 10,973€). With the annual discount of 3.5%, 13.0 (standard deviation 4.8) quality-adjusted life years were gained with the cost of 12,642€ per quality-adjusted life year (interquartile range 15,059€). CONCLUSIONS: We found the use of venoarterial extracorporeal membrane oxygenation in refractory cardiogenic shock and cardiac arrest justified from the cost-utility point of view in a transplant centre setting.

Donor Simvastatin Treatment in Heart Transplantation.

BACKGROUND: Ischemia-reperfusion injury may compromise the short-term and long-term prognosis after heart transplantation. Experimental studies show that simvastatin administered to the organ donor is vasculoprotective and inhibits cardiac allograft ischemia-reperfusion injury. METHODS: Eighty-four multiorgan donors were randomly assigned to receive 80 mg of simvastatin (42 donors) via nasogastric tube after declaration of brain death and upon acceptance as a cardiac donor, or to receive no simvastatin (42 donors). The primary efficacy end point was postoperative plasma troponin T and I levels during the first 24 hours after heart transplantation. Secondary end points included postoperative hemodynamics, inflammation, allograft function, rejections and rejection treatments, and mortality. Results: Organ donor simvastatin treatment significantly reduced the heart recipient plasma levels of troponin T by 34% (14 900 ± 12 100 ng/L to 9800 ± 7900 ng/L, P=0.047), and troponin I by 40% (171 000 ± 151 000 ng/L to 103 000 ± 109 000 ng/L, P=0.023) at 6 hours after reperfusion, the levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) by 36% (32 800 ± 24 300 ng/L to 20 900 ± 15 900 ng/L; P=0.011) at 1 week, and the number of rejection treatments with hemodynamic compromise by 53% within the first 30 days (P=0.046). Donor simvastatin treatment did not affect donor lipid levels but was associated with a specific transplant myocardial biopsy gene expression profile, and a decrease in recipient postoperative plasma levels of CXCL10 (C-X-C motif chemokine 10), interleukin-1α, placental growth factor, and platelet-derived growth factor-BB. Postoperative hemodynamics, biopsy-proven acute rejections, and mortality were similar. No adverse effects were seen in recipients receiving noncardiac solid organ transplants from simvastatin-treated donors. CONCLUSIONS: Donor simvastatin treatment reduces biomarkers of myocardial injury after heart transplantation, and-also considering its documented general safety profile-may be used as a novel, safe, and inexpensive adjunct therapy in multiorgan donation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01160978.

Cancer incidence and mortality after heart transplantation - A population-based national cohort study.

Background: Cancer is currently one of the most important factors affecting the long-term health and survival of heart transplant patients. Material and methods: We calculated the standardized incidence ratios (SIR) for different cancer sites and the cancer-specific standardized mortality ratio (SMR) by linking a cohort of 479 adult heart transplant recipients transplanted in 1985-2014 (4491.6 person-years of follow-up) with data from the national Finnish Cancer Registry until the end of 2015, and with the data from the Statistics Finland's national registry of causes of death. Results: A total of 267 cancers occurred in 143 patients (SIR 6.0; 95% confidence interval (CI) 5.3-6.7). The SIR for overall cancer was considerably higher for men (SIR 6.7; 95% CI 5.9-7.5) than for women (1.4; 95% CI 0.6-2.6). Most frequent cancers were non-melanoma skin cancers (basal cell carcinoma 83 cases, squamous cell skin cancer (SCC) 56 cases), followed by Non-Hodgkin lymphoma (NHL) (36 cases), lung cancer (17), cancer of prostate (16) and cancer of kidney (12). SIRs were highest for SCC (51.9; 95% CI 39.2-67.4), lip cancer (47.4; 95% CI 19.1-97.7), cancer of tongue (26.3; 95% CI 7.2-67.4), and NHL (25.7; 95% CI 18.0-35.6). For most cancers, SIRs increased steadily by time since transplantation. Cancer mortality was three times higher for heart transplant recipients than for the population (SMR 3.1; 95% CI 2.1-4.1). Conclusions: Both cancer incidence and mortality are remarkably increased after heart transplantation, with the relative incidence most elevated for SCC, lip and other oral cancers, and for NHL.

Extracorporeal membrane oxygenation for refractory cardiogenic shock: patient survival and health-related quality of life.

OBJECTIVES: Our goal was to study the outcome of patients with cardiogenic shock who were treated with venoarterial extracorporeal membrane oxygenation (VA ECMO), including the subsequent long-term health-related quality of life (HRQoL). METHODS: We conducted a retrospective study of 133 consecutive patients treated in a single centre from 2007 to 2016. The HRQoL was studied using the EuroQuol-5 dimensions-3 level questionnaire and the RAND 36-Item Short Form Health Survey at a minimum of 1 year after VA ECMO. RESULTS: Of all patients, 66 (49.6%) were weaned from VA ECMO and 16 (12.0%) patients were bridged directly to a transplant, 15 (11.3%) to a ventricular assist device and 1 (0.8%) to a total artificial heart. Survival to discharge was 63.9% and to 1 year, 60.9%. A higher in-hospital mortality rate was independently associated with lower HCO3 at VA ECMO implantation [odds ratio (OR) 1.2/decrease of 1 mmol/l in HCO3 (95% confidence interval 1.1-1.3, P < 0.001)] and with increased need of red blood cells transfused during intensive care [OR 1.9/unit of red blood cells needed/day (95% confidence interval 1.4-2.6, P < 0.001)]. HRQoL measured with the EuroQuol-5 dimensions-3 level questionnaire was equal to the HRQoL of the general population. In the 36-Item Short Form questionnaire, patients reported better emotional well-being and equal energy, pain and general health perception compared to the general population. Limitations were experienced only in physical health. In total, 56% of the patients ≤ 60 years had returned to work. CONCLUSIONS: VA ECMO can provide acceptable long-term survival with good HRQoL for selected patients with refractory cardiogenic shock. Timing of patient assessment and of VA ECMO implantation is essential because deeper acidosis is associated with a higher in-hospital mortality rate.

Low-dose valganciclovir prohylaxis is efficacious and safe in cytomegalovirus seropositive heart transplant recipients with anti-thymocyte globulin.

BACKGROUND: Cytomegalovirus (CMV) remains an important pathogen in solid organ transplant patients. OBJECTIVE: We executed a hybrid prophylactic and pre-emptive valganciclovir (VGCV) prophylaxis to prevent CMV infection in heart transplant patients with anti-thymocyte globulin (ATG) induction and retrospectively evaluated the efficacy and safety of this regimen. METHODS: Hundred adult heart transplant patients between 2004 and 2010 were included. Recipients with CMV serostatus D+/R- received VGCV 900 mg OD for 6 months and 94.2% (81/86) of R+ recipients received a low-dose 450 mg OD for 3 months. Blood CMV was monitored until 3 months after cessation of the prophylaxis. RESULTS: All patients accomplished the prophylaxis. The overall incidence of CMV disease was 4% (4/100) and it was more frequent in D+/R- patients (P = .001). Three of eighty-six (3.5%) of R+ patients had CMV infection (one CMV disease) while on prophylaxis, 2/3 were still on the original significantly reduced renal dose though. There was one late CMV disease in both D+/R- and R+ groups. Ganciclovir/VGCV treatment was successful in all patients. CONCLUSIONS: The hybrid strategy with low-dose VGCV in R+ patients with ATG was efficient and safe. The good treatment results indicate that the regimen did not lead to a clinically relevant resistance. Optimal renal dosage is essential throughout prophylaxis.

Is blockade of the Renin-Angiotensin system able to reverse the structural and functional remodeling of the left ventricle in severe aortic stenosis?

: In experimental aortic stenosis (AS), blockade of the renin-angiotensin system attenuates AS-related left ventricular (LV) dysfunction and improves survival. We tested whether candesartan, an angiotensin II type 1 receptor blocker, favorably influences LV structure and function and improves exercise capacity in AS patients. Fifty-one patients with severe AS were randomized to receive candesartan (target dose 16 mg/d) or placebo. Eight patients discontinued treatment and the remaining 43 patients underwent echocardiography, walking test, and measurement of plasma N-terminal B-type natriuretic peptide (Nt-proBNP) before and after an average of 5-month treatment. No statistically significant changes in LV diameters, mass, or function were seen. The median 6-minute walking distance decreased from 390 to 368 m with candesartan (P = 0.003) and from 380 to 370 m with placebo (P = 0.523), reflecting natural progression of AS. Concomitantly, median Nt-proBNP increased from 319 to 414 ng/L with candesartan (P = 0.170) and from 413 to 561 ng/L with placebo (P = 0.035). No change with candesartan was statistically significantly different from the corresponding change with placebo. In conclusion, candesartan was well tolerated but had no favorable effects on the LV or effort tolerance. The benefits found in experimental AS of blocking the renin-angiotensin system could not be reproduced in patients with severe AS.

[Arranging first aid as voluntary work in Jukola-relay]. / Jukolan viestin 2012 ensiavun järjestäminen talkootyönä.

Various aspects must be anticipated in the planning of first aid in the massive orienteering contest Jukola-relay. Spreading of the event to a wide forest terrain area, beyond the reach of roads, poses a challenge for the evacuation of injured persons. The communication chains must be secured. In addition to the competition center, first aid points must be devised at various off-road points. Capable volunteers must be recruited in sufficient numbers. Establishing a temporary, health center standard emergency preparedness for approximately 50 000 people necessitates the acquisition of equipment and medicines for emergency care. Preparations must be made for the treatment of injuries and attacks of illness among the competitors, the audience and the volunteers.

Circulating collagen metabolites, myocardial fibrosis and heart failure in aortic valve stenosis.

BACKGROUND AND AIM OF THE STUDY: Myocardial fibrosis predisposes to heart failure in aortic valve stenosis. The study aim was to determine the value of: (i) circulating collagen metabolites as biomarkers of left ventricular fibrosis and heart failure in aortic stenosis; and (ii) myocardial fibrosis as a predictor of postoperative outcome. METHODS: Among a total of 132 patients (mean age 68 +/- 10 years) with severe aortic stenosis, measurements were made of circulating N-terminal propeptide of procollagen I (PINP), C-terminal telopeptide of collagen I (CITP) and N-terminal propeptide of procollagen III (PIIINP). Cardiac catheterization, echocardiography and a 6-min walk test were also performed. The aorta-to-coronary sinus concentration gradients of collagen metabolites were determined in 45 patients. Patients free from coronary artery disease (n = 85) underwent left ventricular biopsies for the assessment of myocardial fibrosis, one-year postoperative echocardiography and a 6-min walk test, and a long-term follow up for mortality. RESULTS: Neither peripheral collagen metabolites nor their transcardiac concentration gradients correlated with the extent of myocardial fibrosis. PIIINP demonstrated a net release from the heart, while PINP and CITP showed consistent falls in transcardiac concentrations that suggested extraction rather than release by the heart. Peripheral PIIINP correlated directly with the pulmonary wedge pressure (r = 0.50, p < 0.001) and inversely with the left ventricular ejection fraction (r = -0.40, p = 0.00001) and 6-min walk (r = -0.29, p = 0.001). Similar associations with heart failure were found for CITP, but not for PINP. One-year postoperative changes in exercise capacity and left ventricular mass and function were independent of myocardial fibrosis, as was mortality over a median of 8.8 years. CONCLUSION: Circulating collagen metabolites are not reliable surrogate measures of myocardial fibrosis in aortic stenosis, despite CITP and PIIINP being associated strongly with heart failure and left ventricular dysfunction. The results of surgery, including long-term survival, appear independent of the extent of myocardial fibrosis.

Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of combined immunosuppression.

BACKGROUND: Giant-cell myocarditis often escapes diagnosis until autopsy or transplantation and has defied proper treatment trials for its rarity and deadly behavior. Current therapy rests on multiple-drug immunosuppression but its prognostic influence remains poorly known. We set out to analyze (1) our experience in diagnosing giant-cell myocarditis and (2) the outcome of patients on combined immunosuppression. METHODS AND RESULTS: We reviewed the histories, diagnostic procedures, details of treatment, and outcome of 32 consecutive patients with histologically verified giant-cell myocarditis treated in our hospital since 1991. Twenty-six patients (81%) were diagnosed by endomyocardial or surgical biopsies and 6 at autopsy or post-transplantation. Twenty-eight (88%) patients underwent endomyocardial biopsy. The sensitivity of transvenous endomyocardial biopsy increased from 68% (19/28 patients) to 93% (26/28) after up to 2 repeat procedures. The 26 biopsy-diagnosed patients were treated with combined immunosuppression (2-4 drugs) including cyclosporine in 20 patients. The Kaplan-Meier estimates of transplant-free survival from symptom onset were 69% at 1 year, 58% at 2 years, and 52% at 5 years. Of the transplant-free survivors, 10/17 (59%) experienced sustained ventricular tachyarrhythmias during follow-up and 3 received intracardiac defibrillator shocks for ventricular tachycardia or fibrillation. CONCLUSIONS: Repeat endomyocardial biopsies are frequently needed to diagnose giant-cell myocarditis. On contemporary immunosuppession, two thirds of patients reach a partial clinical remission characterized by freedom from severe heart failure and need of transplantation but continuing proneness to ventricular tachyarrhythmias.

Long-term follow-up of lung and heart transplant recipients with pre-transplant malignancies.

BACKGROUND: Concern regarding recurrence of pre-transplant (Tx) malignancy has disqualified patients from Tx. Because this has been poorly studied in lung and heart Tx recipients our aim was to investigate the influence of pre-Tx malignancy on post-Tx recurrence and long-term survival, focusing on pre-operative cancer-free intervals. METHODS: From our lung and heart Tx programs (1983 to 2011) we retrospectively identified 111 (lung, 37; heart, 74) of 3,830 recipients with 113 pre-Tx malignancies. The patients were divided into 3 groups by pre-Tx cancer-free interval: Group I, <12 months (n = 24); Group II, ≥12 to<60 months (n = 18); and Group III, ≥60 months (n = 71). RESULTS: Mean age at pre-Tx malignancy was 35±18 years. Mean post-Tx follow-up time was 70±63 months (range, 0-278 months), and malignancy recurrence was 63% in Group I, 26% in Group II, and 6% in Group III. Kaplan-Meier analysis of freedom from post-Tx recurrence revealed the following differences among the groups: Group I vs II, p = 0.08; II vs III, p = 0.002; and I vs III, p<0.001. Overall survival (51 deaths) was significantly poorer in Group I than in Groups II and III (p = 0.044). Survival between Groups II and III did not differ significantly (p = 0.93). CONCLUSIONS: Cancer-free survival of ≥5 years pre-Tx is associated with the lowest recurrence. However, recurrence is related to the time the patients were cancer-free, as seen in Groups I and II.

[Mechanical support for the heart and circulation in adults]. / Sydämen ja verenkierron mekaaninen tuki aikuisilla.

In severe, acute or chronic heart failure, the heart and the circulation can be mechanically supported, if the patient's life is in danger despite maximal drug therapy, and other cardiologic or heart surgery treatment options or a suitable heart transplant are not available. Long-term prognosis of those treated with mechanical support has improved in the 2000's. This is based on technically advanced equipment, improved treatment practices, properly targeted patient selection and more accurate timing of therapy.

Pregnancy in heart- and heart/lung recipients can be problematic.

OBJECTIVE: The first successful pregnancy after heart transplantation was reported in 1988. Worldwide experience with heart and heart/lung transplanted (H-HLTx) pregnant women is limited. To expand this knowledge the collaborating Nordic thoracic transplant centers wanted to collect information on all such pregnancies from their centers. DESIGN: Information was retrospectively collected on all H-HLTx pregnancies in the Nordic countries. RESULTS: A total of 25 women have had 42 pregnancies and all survived the gestation. Minor complications were increasing incidence of proteinuria, hypertension and diabetes. Major problems were two rejections (early post partum), two severe renal failures, seven pre-eclampsias and 17 abortions. Five women died two to 12 years after delivery. Of 25 live born children, one was born with cancer and one died early after inheriting the mother's cardiomyopathy. CONCLUSION: Pregnancy after H-HLTx can be successful for both mother and child. There are, however, many obstacles which should be addressed. Respecting the couple's desire for children the attitude should be carefully, not too optimistic, after proper pre-pregnant information and counseling. Delivery should preferably take place at the transplant center.