Prevalence and clinical significance of systolic impairment in hypertrophic cardiomyopathy

Objectives: To determine the frequency of systolic impairment (SI) and its impact on the natural history of hypertrophic cardiomyopathy (HCM).     

Reversal of inappropriate peripheral vascular responses in hypertrophic cardiomyopathy

OBJECTIVES: We assessed the frequency of abnormal forearm vasodilator responses during lower body negative pressure (LBNP) in 21 non-obstructive hypertrophic cardiomyopathy (HCM) patients (31 +/- 8 [20 to 43] years) with abnormal blood pressure response (ABPR) to exercise and the effects of three drugs used to treat vasovagal syncope (propranolol, clonidine, and paroxetine) in a double-blind crossover study. BACKGROUND: Some HCM patients have an ABPR to exercise, which may be due to paradoxical peripheral vasodilatation. A similar proportion has paradoxical forearm vasodilatation during central volume unloading using LBNP. These abnormal reflexes may be caused by left ventricular mechanoreceptor activation. Similar mechanisms may also contribute to some cases of vasovagal syncope. METHODS: Blood pressure changes were assessed during exercise, and forearm vascular responses and baroreceptor sensitivity were assessed during LBNP using plethysmography. RESULTS: Nine (43%) patients (group A) had paradoxical vasodilator responses (forearm vascular resistance [FVR] fell by 7.5 +/- 4.6 U), and 12 (57%) patients (group B) had normal vasoconstrictor responses during LBNP (FVR increased by 7.7 +/- 4.9 U). Paroxetine augmented systolic blood pressure (SBP) during exercise in group A (21 +/- 6 mm Hg vs. 14 +/- 11 mm Hg at baseline, p = 0.02); no effect was detected in group B. Paroxetine reversed paradoxical vascular responses during LBNP in seven (78%) patients from group A. Propranolol and clonidine had no significant effect on SBP during exercise but reversed paradoxical vascular responses in some patients from group A (n = 5 and n = 3). CONCLUSIONS: Paradoxical vasodilatation during LBNP occurs in 40% of patients with ABPR during exercise and is reversed by propranolol, clonidine, and paroxetine. Paroxetine also improved SBP response to exercise.     

Haematogones in the peripheral blood of adults: a four-colour flow cytometry study of 102 patients

Haematogones have been extensively characterized in bone marrow, but not in the peripheral blood (PB). We studied 102 PB samples from adult patients with a sensitive flow cytometry method. Sixty-six of 102 samples (65%) contained detectable haematogones, ranging from 0.01% to 1.3% of white blood cells (median 0.06%, mean 0.13%). Of 66 cases with complete blood count data, 51 had absolute haematogone counts of 0.00037-0.105 x 10(9)/l (median 0.0054 x 10(9)/l, mean 0.012 x 10(9)/l). PB haematogones belonged exclusively to the most mature maturational stage. These findings have implications for PB analysis of minimal residual disease in acute lymphoblastic leukaemia and follicular lymphoma.     

Hypocellular acute leukemia

We examined the clinical features and therapeutic response of a group of patients with acute leukemia and hypocellular bone marrow. Therapists have generally avoided, delayed or modified therapy because of hypocellularity. We demonstrated not only that aggressive therapy is possible, but also that the remission rate is high (complete remission = 73 percent) and survival prolonged (x? > 40 months).     

Health related quality of life and psychological wellbeing in patients with dilated cardiomyopathy

OBJECTIVE—To assess the health related quality of life and psychological wellbeing of patients with dilated cardiomyopathy, and relate these to clinical variables and psychological adjustment.
DESIGN—Postal questionnaire survey of 99 adult patients with dilated cardiomyopathy, selected at random from a larger database (60.6% response rate). Assessments included the short form 36 (SF-36) health survey, the hospital anxiety and depression scales, the sleep problems index, and a measure of psychological adjustment to cardiomyopathy.
RESULTS—Patients with dilated cardiomyopathy reported significant impairments in physical functioning, role limitations owing to physical and emotional problems, social functioning, mental health, perceptions of general health, sleep, and vitality. Anxiety and depression levels were higher than in population samples. Impairment in several domains of quality of life was associated with low shortening fraction, high left ventricular end diastolic diameter, and the presence of heart failure and mitral regurgitation. Patients with familial cardiomyopathy had less impairment in quality of life than those with non-familial disease. Psychological adjustment scores were associated with several aspects of quality of life and emotional wellbeing. In multivariate analysis, demographic and clinical variables accounted for 0.1-40.7% of the variance in different domains of quality of life, and psychological adjustment scores accounted for an additional 0.5-22.4% of variance.
CONCLUSIONS—Patients with dilated cardiomyopathy experience pronounced restrictions in quality of life and psychological wellbeing. These limitations are only partly accounted for by symptoms and the severity of underlying disease. Patients may benefit from efforts to improve psychological adjustment to the condition.


Keywords: dilated cardiomyopathy; quality of life; adjustment; wellbeing     

Differences and Similarities between Culture-Confirmed Human Granulocytic Anaplasmosis and Early Lyme Disease

Lyme disease is transmitted by the bite of certain Ixodes ticks, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Although culture can be used to identify patients infected with A. phagocytophilum and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms (P = 0.003) and had a higher body temperature on presentation (P < 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho = 0.389, P = 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease.     

To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.