Calcific aortic valve stenosis constitutes a significant health problem in the elderly. Only a minority of those with potentially operable aortic valve stenosis undergo surgery.

G iant-cell myocarditis (GCM) is known as a rare, rapidly progressive, and frequently fatal myocardial disease in young and middle-aged adults. It is attributed to a T lymphocyte-mediated inflammation of the heart muscle and associates with systemic autoimmune diseases in ≈20% of cases. 1,2The most common early manifestations are heart failure, ventricular arrhythmias, and atrioventricular block, but GCM may also disguise as an acute myocardial infarction and rarely presents as an unexpected sudden cardiac death.1-3 The diagnosis of GCM rests fully on microscopy of the heart muscle and even in experienced centers >4 in 10 cases may escape detection until autopsy or cardiac transplantation. Aside from nonspecific measures to combat its symptomatic manifestations, the treatment of GCM relies on immunosuppression. Retrospective observations from the Multicenter GCM Registry 1,4 and a small prospective study with repeat biopsies 5 suggest that cyclosporine-based combined immunosuppression may be able to reduce myocardial inflammation 5 and improve clinical outcome. 1,4,5 Yet, these data are uncontrolled and suffer from lack of details about the treatments given 1,4 and the possibility of survivor bias. 1,4,5 The key problem is that the rarity and seriousness of GCM make controlled treatment trials, let alone use of a placebo arm, virtually impossible. The only such attempt, a cooperative endeavor by 17 centers, was terminated after 6 years because of difficulties in recruiting patients.5 Therefore, carefully studied observational patient series continue to add to the knowledge about GCM. We report here our experience in 32 patients with GCM, of whom 26 received combined immunosuppression. We focus on the diagnosis of GCM and on the outcome of patients with contemporary treatment. Our key observations suggest that repeat and imaging-guided biopsies increase the detection rate of GCM and that combined immunosuppression supported by therapy for heart failure and arrhythmias may result in transplant-free survival in two thirds of patients. Clinical Perspective on p 22 Methods PatientsFrom the year 1991 through 2011, 32 patients with histologically verified GCM were seen at the Division of Cardiology, Helsinki University Central Hospital. The majority of diagnoses (29/32) were made after year 2000, that is, during the latter half of the study period. The medical records, laboratory test, imaging studies, and available biopsy material of all patients were retrospectively reviewed and © 2012 American Heart Association, Inc. 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, a...

Background-This study was designed to assess the epidemiology, characteristics, and outcome of cardiac sarcoidosis (CS) in Finland. Methods and Results-We identified in retrospect all adult (>18 years of age) patients diagnosed with histologically confirmed CS in Finland between 1988 and 2012. A total of 110 patients (71 women) 51±9 years of age (mean±SD) were found and followed up for outcome events to the end of 2013. The annual detection rate of CS increased >20-fold during the 25-year period, reaching 0.31 in 1×10 5 adults between 2008 and 2012. The 2012 prevalence of CS was 2.2 in 1×10 5 . Nearly two thirds of patients had clinically isolated CS. Altogether, 102 of the 110 patients received immunosuppressive therapy, and 56 received an intracardiac defibrillator. Left ventricular function was impaired (ejection fraction <50%) in 65 patients (59%) at diagnosis and showed no overall change over 12 months of steroid therapy. During follow-up (median, 6.6 years), 10 patients died of a cardiac cause, 11 patients underwent transplantation, and another 11 patients suffered an aborted sudden cardiac death. The Kaplan-Meier estimates for 1-, 5-, and 10-year transplantation-free cardiac survival were 97%, 90%, and 83%, respectively. Heart failure at presentation predicted poor outcome (log-rank P=0.0001) with a 10-year transplantation-free cardiac survival of only 53%. Conclusions-The detection rate of CS has increased markedly in Finland over the last 25 years. With current therapy, the prognosis of CS appears better than generally considered, but patients presenting with heart failure still have poor longterm outcome. (Circulation. 2015;131:624-632.

Abstract. Kandolin R, Lehtonen J, Graner M, Schildt

Genetic variations in or near the aldosterone synthase (CYP11B2) gene strongly affect left ventricular size and mass in young adults free of clinical heart disease. These polymorphisms may also influence the response of the left ventricle to increases in dietary salt.

Background-Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) may present as high-degree atrioventricular block (AVB), but their proportion of the causal spectrum of AVB is not well-known. We investigated the prevalence of biopsy-verified CS and GCM in young and middle-aged adults undergoing pacemaker (PM) implantation for AVB. Methods and Results-We used the PM registry of Helsinki University Central Hospital to identify all patients aged 18 to 55 years who underwent PM implantation for AVB between January 1999 and April 2009 and reviewed their medical records. In total, 133 patients had either second-or third-degree AVB as an indication for PM. Of them, 61 had a known cause for AVB, and they were excluded from further analyses. Among the remaining 72 patients with initially unexplained AVB, biopsy-verified CS or GCM was found in 14 (19%) and 4 (6%) patients, respectively. The majority (16/18, 89%) were women. Among the adult patients aged Ͻ55 years, the prevalence of CS and GCM combined was 14% (95% CI, 7.7% to 19.3%) of the whole AVB population and 25% (95% CI, 15% to 35%) of those with an initially unexplained AVB. Over an average of 48 months of follow-up, 7 (39%) of 18 patients with CS or GCM versus 1 of the 54 patients in whom AVB remained idiopathic, experienced either cardiac death, cardiac transplantation, ventricular fibrillation, or treated sustained ventricular tachycardia (PϽ0.001). Conclusions-CS and GCM explain Ն25% of initially unexplained AVB in young and middle-aged adults. These patients are at high risk for adverse cardiac events. (Circ Arrhythm Electrophysiol. 2011;4:303-309.)

This study aimed at identifying factors influencing aortic valve calcification in old age. Echocardiographic and Doppler characteristics of the aortic valve were compared with possible clinical and biochemical predictors in 501 people aged 75-86 years and in 76 aged 55-71. Slight calcification was seen in 222 people (40%) and severe calcification in 72 (13%); 21 people had moderate or severe aortic stenosis. Age (P = 0.000) and serum parathyroid hormone (P = 0.015) were higher and body mass index lower (P = 0.002) in the presence of aortic valve calcification. In multivariate analysis, age (P = 0.000), hypertension (P = 0.005) and body mass index (P = 0.005) were independent predictors of aortic valve calcification, and age (P = 0.022) and serum ionized calcium (P = 0.037) of valve stenosis. The odds ratio (95% confidence interval) for valve calcification was 1.89 (1.42-2.50) for a 10-year increase in age, 1.74 (1.19-2.55) in the presence of hypertension, and 1.39 (1.10-1.76) for a 5 kg.m-2 decrease in body mass index. Sex, smoking, diabetes, serum lipids and insulin were unrelated to valvular calcification. These data suggest that leanness and a history of hypertension increase the likelihood of senile aortic valve calcification. Calcium metabolism may also be of significance. The mechanisms of these associations deserve further study.

Angiotensin-converting enzyme and chymase, two Ang II-forming enzymes, are locally expressed in aortic valves, and owing to infiltration of macrophages and MCs, are further upregulated in stenotic valves. These novel findings, implicating chronic inflammation and an increased expression of local Ang II-forming systems, suggest that therapeutic interventions aiming at inhibiting these processes may slow AS progression.