Cardiac involvement with amyloidosis: mechanisms of disease, diagnosis and management

The amyloidoses represent a group of clinical disorders of diverse etiologies that have as a common pathophysiologic denominator the deposition of misfolded protein based amyloid fibrils in the interstitial space of various organs. They are uncommon diseases with protean clinical presentations. Cardiac involvement is the determining factor for a patient's prognosis. Clinicians have to maintain a high index of suspicion and actively search for signs and symptoms of cardiac involvement in patients with preexisting conditions known to be associated with the development of amyloidosis. Early diagnosis and accurate fibril typing are the first steps in managing the disease. Judicious use of various diagnostic modalities such as serum markers and imaging studies, and good communication among all the physicians involved in the care of these sick and frail patients, are keys to a better outcome

Basal infarct location but not larger infarct size is associated with a successful outcome after alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy: a cardiovascular magnetic resonance imaging study

Alcohol septal ablation (ASA) is successful in most but not in all patients with obstructive hypertrophic cardiomyopathy (HCM). We therefore sought to investigate the relation between infarct location versus infarct size with outcome after ASA in patients with obstructive HCM. Baseline characteristics, procedural characteristics, and cardiovascular magnetic resonance findings at baseline and 4-6 month follow-up after ASA were analysed in 47 patients with obstructive HCM in a single-center retrospective study. Infarct size was determined using late gadolinium enhancement. Infarct location was divided into "basal infarction" and "distal infarction" based on an optimal cut-of value of the distance from the basal septum to the beginning of the infarction. A "successful" outcome was defined as 80 % reduction of the invasive gradient with a post-procedural gradient of <10 mmHg. Basal infarctions (n = 31) compared to distal infarctions (n = 16) were associated with successful outcome (100 vs. 38 %, P <0.001). Larger infarct size (n = 20) compared to smaller infarct size (n = 27) was not associated with successful outcome (75 vs. 82 %, P = 0.72). A more distal location of the infarction, was the only predictor of a less successful outcome (odds ratio 0.76, 95 % confidence interval 0.54-0.98, P = 0.03). Basal versus distal infarctions were also associated with a lower provoked gradient at late (2.6 +/- A 2.2 years) follow-up (11 (6-20) vs. 27 (12-94) mmHg, P = 0.01). Basal infarctions were associated with a successful outcome after ASA. A larger infarct size was not associated with a better outcome

Carriers of the hypertrophic cardiomyopathy MYBPC3 mutation are characterized by reduced myocardial efficiency in the absence of hypertrophy and microvascular dysfunction

Next to left ventricular (LV) hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by microvascular dysfunction and reduced myocardial external efficiency (MEE). Insights into the presence of these abnormalities as early markers of disease are of clinical importance in risk stratification, and development of therapeutic approaches. Therefore, the aim was to investigate myocardial perfusion and energetics in genotype-positive, phenotype-negative HCM subjects (carriers). Fifteen carriers of an MYBPC3 mutation underwent [(15)O]water positron emission tomography (PET) to assess myocardial blood flow (MBF). [(11)C]acetate PET was performed to obtain myocardial oxygen consumption (MVO(2)). By use of cardiovascular magnetic resonance imaging, LV volumes and mass were defined to calculate MEE, i.e. the ratio between external work and MVO(2). Eleven healthy, genotype-negative, family relatives underwent similar scanning protocols to serve as a control group. Left ventricular mass was comparable between carriers and controls (93 ± 25 vs. 99 ± 21 g, P= 0.85), as was MBF at rest (1.19 ± 0.34 vs. 1.18 ± 0.32 mL min(-1) g(-1), P= 0.92), and during hyperaemia (3.87 ± 0.75 vs. 3.96 ± 0.86 mL min(-1) g(-1), P= 0.77). Myocardial oxygen consumption averaged 0.137 ± 0.057 mL min(-1) g(-1) in carriers and was not significantly different from controls (0.125 ± 0.043 mL min(-1) g(-1), P= 0.29). Cardiac work, however, was slightly reduced in carriers (7398 ± 1384 vs. 9139 ± 2484 mmHg mL in controls, P= 0.08). As a consequence, MEE was significantly decreased in carriers (27 ± 10 vs. 36 ± 8% in controls, P= 0.02). Carriers display reduced myocardial work generation in relation to oxygen consumption, in the absence of hypertrophy and flow abnormalities. Hence, impaired myocardial energetics may constitute a primary component of HCM pathogenesi

Hyperhomocysteinemia, pregnancy complications, and the timing of investigation.

Item does not contain fulltextOBJECTIVE: To assess associations between vitamin-dependent homocysteine metabolism and vascular-related pregnancy complications by considering interval between delivery and postpartum investigation and maternal age. METHODS: Case-control study performed at the University Medical Center Nijmegen in the Netherlands. Patients had experienced pregnancy-induced hypertension (n = 37), preeclampsia (n = 144), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 104), recurrent early pregnancy loss (n = 544), abruptio placentae (n = 135), intrauterine growth restriction (n = 144), or intrauterine fetal death (n = 104). Controls comprised 176 women with uncomplicated obstetric histories. Oral methionine loading tests and fasting vitamin profiles were performed more than 6 weeks after delivery. Odds ratios and 95% confidence intervals were calculated after logistic regression analysis. RESULTS: Hyperhomocysteinemia was associated with an approximately 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abruptio placentae, and intrauterine growth restriction. Cobalamin deficiency was associated with HELLP syndrome, abruptio placentae, intrauterine growth restriction, and intrauterine fetal death. Pyridoxal 5-phosphate deficiency increased the risk for pregnancy-induced hypertension 4-fold. These associations lost their significance after adjustment for time interval and maternal age. High red cell folate was associated with a decreased risk for abruptio placentae and intrauterine growth restriction. An increased creatinine concentration was associated with pregnancy-induced hypertension, preeclampsia, HELLP syndrome, and abruptio placentae. CONCLUSION: Hyperhomocysteinemia and vitamin deficiencies are largely determined by the interval between delivery and postpartum investigation and by maternal age. Time interval and maternal age should be considered in the risk estimation for vascular-related pregnancy complications