Jacek S. Dubiel

Late hyperenhancement in gadolinium-enhanced magnetic resonance imaging: comparison of hypertrophic cardiomyopathy patients with and without nonsustained ventricular tachycardia

AimTo assess the extent of hyperenhancement in hypertrophic cardiomyopathy (HCM) patients with nonsustained ventricular tachycardia (NSVT) in comparison to patients without NSVT.DesignIn HCM patients, NSVT in Holter monitoring is a risk factor for sudden cardiac death; however, its positive predictive value is low. Varying risk of sudden death related to NSVT may be dependent on the heterogeneous extent of the arrhythmogenic substrate, which seems to be visible as hyperenhancement in gadolinium-enhanced magnetic resonance imaging (MRI).MethodsHyperenhancement was assessed in 47xa0HCM patients (30 males and 17 females, mean age 42xa0±xa012xa0years): 32 patients had NSVT, 15 patients had no NSVT. The extent of hyperenhancement was calculated by software and expressed as a mass.ResultsIn HCM patients with NSVT 97% had some extent of hyperenhancement on MRI, ranging from 1 to 76xa0g. The mean mass of hyperenhanced myocardium was 19xa0±xa018xa0g (8.1xa0±xa07.6% of total left ventricular mass). In HCM patients without NSVT, a significantly lower percentage of patients (60%) had hyperenhancement (Pxa0<xa00.05). However, the amount of hyperenhanced myocardium was not significantly different (13xa0±xa019xa0g, 6.3xa0±xa09.1% of total left ventricular mass; Pxa0<xa00.05).ConclusionsHyperenhancement was visible in almost all HCM patients with NSVT (97%) and in a significantly lower percentage of patients without NSVT (60%). Whether this finding explains the increased risk of sudden death in case of NSVT is not clear, since the extent of hyperenhancement was not significantly different between the two groups.

Plasma asymmetric dimethylarginine is related to anticitrullinated protein antibodies in rheumatoid arthritis of short duration

We have recently demonstrated elevated plasma levels of an endogenous nitric oxide synthase inhibitor, asymmetric dimethyl-L-arginine (ADMA), and its association with carotid atherosclerosis in rheumatoid arthritis (RA). Both an elevated risk of myocardial infarction and increased levels of anticitrullinated protein antibodies (ACPAs), specific for RA, had been shown to precede the onset of clinical RA symptoms. Therefore, our aim was to verify the hypothesis that ADMA accumulation might accompany raised ACPAs titers in RA of short duration (< or = 3 years). Twenty patients (16 women, 4 men; mean age, 45 +/- 12 years; mean disease duration, 2.3 +/- 0.5 years) with active RA despite chronic disease-modifying antirheumatic medication, free of cardiovascular disease or atherosclerotic risk factors, were studied. Plasma levels of ADMA and its stereoisomer, symmetric dimethyl-L-arginine (SDMA), were assayed by liquid chromatography/tandem mass spectrometry. The ACPAs were measured by a second-generation enzyme-linked immunosorbent assay. In addition to routine biochemical assays, plasma concentrations of tumor necrosis factor alpha, monocyte chemoattractant protein-1, and vascular cell adhesion molecule-1 soluble form were analyzed with respective enzyme-linked immunosorbent assays. A significant positive correlation between levels of ACPAs and ADMA (r = .60, P = .005), but not SDMA (r = -.02, P = .9), was found. Neither ADMA nor SDMA was correlated to any of the clinical or biochemical parameters reflecting disease activity and inflammatory activation. Thus, excessive ADMA accumulation accompanies elevated ACPAs levels in patients with RA of short duration free of cardiovascular disease or risk factors.

The influence of age on gender-specific differences in the left ventricular cavity size and contractility in patients with hypertrophic cardiomyopathy

BACKGROUNDnThe aim of the study was to assess gender-specific differences in left ventricular cavity size, contractility and left ventricular outflow tract obstruction in younger and older subgroups of patients with hypertrophic cardiomyopathy.nnnMETHODSnWe studied retrospectively 153 referred patients with hypertrophic cardiomyopathy (89 males and 64 females). The echocardiographically measured left ventricular end-systolic, end-diastolic dimensions, fractional shortening and occurrence of left ventricular outflow tract gradient were compared between sexes in subgroups of patients </=50 and >50 years of age.nnnRESULTSnIn younger patients with hypertrophic cardiomyopathy, left ventricular end-diastolic and end-systolic dimensions were significantly smaller in females than males (41.9+/-5.8 vs. 44.7+/-5 mm P<0.01 23.4+/-5 vs. 25.2+/-5.4 mm P<0.05, respectively). Fractional shortening was comparable in both sexes (44.7+/-7.5 vs. 43.7+/-8.2% P>0.05). The left ventricular outflow tract gradient occurred in females as frequently as in males (13.3 vs. 17.6% P>0.05). In older patients with hypertrophic cardiomyopathy, left ventricular end-diastolic and end-systolic dimensions were also significantly smaller in females than males (42.5+/-6 vs. 46.3+/-3.2 mm P<0.02; 25.7+/-4.8 vs. 28.6+/-3.7 mm P<0.01, respectively). In contrast to the younger group, the fractional shortening was significantly higher in females than males (44.4+/-6.8 vs. 38.2+/-7.3% P<0.02). The left ventricular outflow tract gradient occurred in females more frequently than in males (63.2 vs. 20.8% P<0.02).nnnCONCLUSIONSnIn patients with hypertrophic cardiomyopathy, the gender-based differences in the absolute value of left ventricular cavity size persisted with aging. In older females left ventricular contractility was higher and left ventricular outflow tract gradient occurred more frequently than in males. In younger patients with hypertophic cardiomyopathy these sex-based differences were absent. The gender-specific differences in the parameters of left ventricular systolic function became apparent with increasing age.

Enhanced oxidative stress in hypertrophic cardiomyopathy

Elevated plasma levels of inflammation and endothelial dysfunction markers have been reported in patients with hypertrophic cardiomyopathy (HCM). The aim of the current study was to determine whether HCM is associated with enhanced oxidative stress. We enrolled 54 HCM patients with sinus rhythm, including 21 subjects with a left ventricular outflow tract (LVOT) obstruction (gradient >/= 30 mmHg), and 54 age- and sex-matched controls without cardiovascular diseases. Serum levels of 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), a stable marker of oxidative stress, were determined. Serum 8-iso-PGF(2alpha) levels were elevated in HCM patients compared with controls (35.4 +/- 10.2 vs. 29.9 +/- 9.9 pg/ml, p < 0.001). Patients with obstructive HCM displayed higher 8-iso-PGF(2alpha) levels compared with the non-obstructive HCM subgroup (41.6 +/- 12.7 vs. 31.4 +/- 5.4 pg/ml, p < 0.0001). Both anatomic (mitral-septal distance) and hemodynamic (subaortic gradient) indexes of LVOT obstruction, but not other echocardiographic variables, correlated with 8-iso-PGF(2alpha) levels (r = -0.43; p < 0.05 and r = 0.39; p < 0.05, respectively). This study is the first to show that HCM is characterized by enhanced oxidative stress as evidenced by higher 8-iso-PGF(2alpha), which achieves its highest values in the presence of LVOT obstruction in HCM patients.

Comparison of the Effect of Verapamil and Propranolol on Response of Coronary Vasomotion to Cold Pressor Test in Symptomatic Patients with Hypertrophic Cardiomyopathy

Impaired endothelium-dependent vasodilatation of coronary resistance vessels has been demonstrated in patients with hypertrophic cardiomyopathy (HC). The aim of this study was to compare the effect of verapamil and propranolol on the response of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance index to the cold pressor test (CPT) in symptomatic HC patients. In 15 patients with HC, the CBFV was measured in the distal portion of the left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. Peak diastolic CBFV and coronary vascular resistance index (calculated as ratio of mean aortic pressure/CBFV ratio) were measured at baseline and after CPT. Changes of these parameters induced by the CPT (expressed as percentage of baseline values) were compared after verapamil and propranolol treatment in a crossover study. The same measurements were obtained in nine healthy control subjects. CPT induced an increasing pattern of CBFV during verapamil therapy, which was absent in CPT after propranolol administration (10.1 ± 5.6% vs. −0.9 ± 4.1%, P < 0.01). In healthy controls CBFV increased in response to CPT more than in HC patients receiving verapamil or propranolol (23.1±12.8% P < 0.01 and P < 0.05, respectively). The coronary vascular resistance index increased during the CPT significantly less on verapamil than on propranolol treatment (3.5 ± 9.2% vs. 18.1 ± 13.5%, P < 0.01). In healthy controls the coronary vascular resistance index decreased during CPT −4.5 ± 8.5% (P < 0.05 vs. verapamil and P < 0.01 vs. propranolol). Verapamil improved the coronary vasomotor response to CPT in relation to propranolol. Verapamil blunted the increase of the coronary vascular resistance index to the CPT in comparison with its change at CPT after propranolol. Thus, coronary endothelial dysfunction in symptomatic HC patients may be partially reduced by verapamil in comparison with propranolol treatment.

Verapamil improves the response of coronary vasomotion to cold pressor test in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy.

Summary. Impaired endothelium-dependent vasodilatation of coronary resistance vessels was previously demonstrated in patients with hypertrophic cardiomyopathy (HC). Therefore, we decided to assess the effect of verapamil administration on the response of diastolic coronary blood flow velocity (CBFV) and the coronary vascular resistance index to the cold pressor test in asymptomatic and mildly symptomatic HC patients. In 10 patients with nonobstructive HC, the CBFV was detected in the distal portion of the left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. Peak diastolic CBFV, the velocity-time integral of diastolic CBF, and the coronary vascular resistance index (calculated as the mean aortic pressure/CBFV ratio) were measured at baseline and after the cold pressor test. The percentage changes from baseline to the cold pressor test of these parameters were compared before and after 1 month of verapamil therapy. Open-label verapamil changed the decrease in CBFV into an increase in response to the cold pressor test (from −4.1 ± 6.4% to +11 ± 10.9%, P < 0.01). A similar reversibility of changes in the velocity–time integral of CBF in response to the cold pressor test after verapamil therapy was observed (from −3.3 ± 8.3% to +9.6 ± 10.3%, P < 0.05). Verapamil reversed the response of coronary resistance vessels to the cold pressor test from a +12 ± 9.8% increase to a −5.2 ± 10.2% decrease in the coronary vascular resistance index (P < 0.01). We concluded that in asymptomatic and mildly symptomatic HC patients in response to the cold pressor test, treatment with open-label verapamil increased CBF parameters and decreased the coronary vascular resistance index. Verapamil reversed the abnormal vasoconstrictor to vasodilator response of coronary resistance vessels to the cold pressor test. The restoration of the vasodilator response to the by verapamil cold pressor test suggests the potential positive effect of verapamil on endothelium-dependent coronary vasodilatation in HC patients. Thus, a randomized blinded trial is now required.

Sex Differences in Age at Onset of Symptoms in Patients with Hypertrophic Cardiomyopathy

Background We hypothesized that, in hypertrophic cardiomyopathy, endogenous estrogen may delay the development of symptoms in females as compared with males by several cardiovascular protective mechanisms, We examined this by assessing the sex distribution in relation to age at onset of symptoms in patients with hypertrophic cardiomyopathy, Methods The study population of 94 patients (55 men and 39 women) was subdivided into four groups according to age at onset of symptoms: < 15 years, 15-29 years, 30-39 years and > 40 years. In the first group, comprising the youngest patients, all the girls were pre-menarche. The age of 40 years was chosen as the lower limit for the last group because of the possible influence of pre- and perimenopausal decrease in estrogen levels on the onset of symptoms in women in their fifth decade of life. Results In general, females with hypertrophic cardiomyopathy developed symptoms later than did males (31.3 ± 11.9 compared with 26.7 ± 9.9 years; P < 0.05). Among adolescents, similar percentages of girls and boys developed the condition. Among young adult patients (between 15 and 29 years of age), it was predominantly men who developed symptoms, Men predominated, albeit insignificantly, among patients with onset of symptoms in the fourth decade of life, but there was a significant dominance of women over men in the group who became symptomatic after 40 years of age. Conclusion Delayed onset of symptoms in women with hypertrophic cardiomyopathy compared with men resulted in nearly one-third of women remaining asymptomatic until 40 years of age, symptoms developing in the fifth decade of life.

The costs of heart failure in Poland from the public payer’s perspective. Polish programme assessing diagnostic procedures, treatment and costs in patients with heart failure in randomly selected outpatient clinics and hospitals at different levels of car

BACKGROUNDnHeart failure (HF) is a chronic disease of great clinical and economic significance for both the healthcare system and patients themselves.nnnAIMnTo determine the consumption of medical resources for treatment and care of HF patients and to estimate the related costs.nnnMETHODSnThe study involved 400 primary care practices and 396 specialist outpatient clinics, as well as 259 hospitals at all reference levels. The sample was representative and supplemented with patient interview data. Based on the consumption of particular resources and the unit costs of services in 2011, costs of care for HF patients in Poland were estimated. Separate analyses were conducted depending on the stage of the disease (according to NYHA classification I-IV). The public payers perspective and a one year time horizon were adopted.nnnRESULTSnDirect annual costs of an HF patients treatment in Poland may range between PLN 3,373.23 and 7,739.49 (2011), the main cost item being hospitalisation. The total costs for the healthcare system could be as high as PLN 1,703 million, which is 3.16% of the National Health Funds budget (Ex. rate from 05.03.2012: 1 EUR = 4.14 PLN).nnnCONCLUSIONSnThe costs of treating heart failure in Poland are high; proper allocation of resources to diagnostic procedures and treatment may contribute to rationalisation of the relevant expenditure.

Effects of acute euglycemic hyperinsulinemia on urinary nitrite/nitrate excretion and plasma endothelin-1 levels in men with essential hypertension and normotensive controls

Insulin stimulates the production of endothelin-1 (ET-1) and nitric oxide (NO) by isolated endothelial cells. Additionally, insulin-dependent glucose transport and insulin-mediated NO production partially share common elements in signal transduction. There are discordant data on plasma ET-1 levels during acute euglycemic systemic hyperinsulinemia in normotensive men and men with essential hypertension (EH) (known to be insulin-resistant), as well as on the relations between insulin sensitivity and vascular function. Our aim was to assess the response of approximate measures of whole-body generation of NO and ET-1 to acute euglycemic hyperinsulinemia in EH patients and controls. We studied 17 newly diagnosed untreated men with uncomplicated EH and 10 normotensive controls. Plasma ET-1 and urinary excretion of nitrite plus nitrate, stable NO metabolites (Uno(x)), were measured before and during a 3-hour hyperinsulinemic-euglycemic clamp. Both in hypertensives and normotensives, plasma ET-1 levels were reduced after 2 hours of the clamp (EH: baseline, 3.1+/-1.9 pg/mL; 2 hours, 1.9+/-1.2 pg/mL, P = .04 v baseline; controls: baseline, 4.2+/-2.6 pg/mL; 2 hours, 2.8+/-1.4 pg/mL, P = .04 v baseline). No significant changes in Uno(x) during the clamp were observed. Changes in Uno(x) during the clamp (deltaUno(x)) and differences in plasma ET-1 measured before the end and before the beginning of the clamp (deltaET-1) were correlated in the controls (r = .75, P = .01) but not in EH (r = -.01, P = .97). No parameter of glucose metabolism correlated with basal Uno(x), basal plasma ET-1, deltaUno(x), and deltaET-1, whether absolute or percent values, in either group. Thus, acute euglycemic hyperinsulinemia produces a decrease in plasma ET-1 in both EH patients and controls. The lack of correlation between deltaUno(x) and deltaET-1 under these conditions in EH may suggest an impairment of systems governing interactions between the NO-dependent pathway and ET-1. In addition, insulin actions on glucose metabolism and on the endothelial mediators appear dissociated.

Coronary flow reserve and exercise capacity in hypertrophic cardiomyopathy

SummaryThe aim of this study was to evaluate the relation of coronary flow velocity (CFV) and coronary flow reserve (CFR) to exercise capacity in ten verapamil-treated patients with hypertrophic cardiomyopathy (HC). Using Doppler transesophageal echocardiography, we assessed diastolic CFV in the proximal left anterior descending coronary artery at baseline and after administering 0.56 mg/kg intravenous dipyridamole. The CFR was calculated as the postdipyridamole/baseline diastolic CFV ratio. A maximal symptom-limited exercise treadmill test was performed according to a modified Bruce protocol and the exercise capacity was expressed as metabolic equivalents. The mean value for baseline diastolic CFV was 59 ± 27cm/s; this increased after dipyridamole to 134 ± 57cm/s. The CFR was 2.37 ± 0.67. Baseline diastolic CFV correlated negatively with both exercise duration (r = −0.69;P < 0.05) and value for metabolic equivalents (r = −0.70;P < 0.05). CFR was weakly and non-significantly related to exercise duration (r = 0.40;P > 0.05) and to the value for metabolic equivalents (r = 0.32;P > 0.05). Shortening of exercise time and decreasing metabolic equivalents were correlated with increased baseline diastolic CFV. Dipyridamole-assessed CFR, was weakly related to parameters of exercise capacity.