Danuta Czarnecka

Pulsatile but Not Steady Component of Blood Pressure Predicts Cardiovascular Events in Coronary Patients

Although the differences between central and peripheral blood pressure (BP) values have been known for decades, the consequences of decision making based on peripheral rather than central BP have only recently been recognized. There are only a few studies assessing the relationship between intraaortic BP and cardiovascular risk. In addition, the relationship between central BP and the risk of cardiovascular events in a large group of coronary patients has not yet been evaluated. Therefore, the aim of the study was to determine the prognostic significance of central BP-derived indices in patients undergoing coronary angiography. Invasive central BPs were taken at baseline, and study end points were ascertained during over a 4.5-year follow-up in 1109 consecutive patients. The primary end point (cardiovascular death or myocardial infarction or stroke or cardiac arrest or heart transplantation or myocardial revascularization) occurred in 246 (22.2%) patients. Central pulsatility was the most powerful predictor of the primary end point (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.14 to 1.48). Central pulse pressure was also independently related to the primary end point (HR 1.25, 95% CI 1.09 to 1.43). Central mean BP as well as peripheral BP parameters were not independently related to the primary end point risk. Central pulsatility was also related to risk of cardiovascular death or myocardial infarction or stroke. The pulsatile component of BP is the most important factor related to the cardiovascular risk in coronary patients. It is more closely associated with cardiovascular risk than steady component of BP.

Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure

AIMS Periodic breathing with central sleep apnoea (CSA) is common in heart failure patients and is associated with poor quality of life and increased risk of morbidity and mortality. We conducted a prospective, non-randomized, acute study to determine the feasibility of using unilateral transvenous phrenic nerve stimulation for the treatment of CSA in heart failure patients. METHODS AND RESULTS Thirty-one patients from six centres underwent attempted transvenous lead placement. Of these, 16 qualified to undergo two successive nights of polysomnography-one night with and one night without phrenic nerve stimulation. Comparisons were made between the two nights using the following indices: apnoea-hypopnoea index (AHI), central apnoea index (CAI), obstructive apnoea index (OAI), hypopnoea index, arousal index, and 4% oxygen desaturation index (ODI4%). Patients underwent phrenic nerve stimulation from either the right brachiocephalic vein (n = 8) or the left brachiocephalic or pericardiophrenic vein (n = 8). Therapy period was (mean ± SD) 251 ± 71 min. Stimulation resulted in significant improvement in the AHI [median (inter-quartile range); 45 (39-59) vs. 23 (12-27) events/h, P = 0.002], CAI [27 (11-38) vs. 1 (0-5) events/h, P≤ 0.001], arousal index [32 (20-42) vs. 12 (9-27) events/h, P = 0.001], and ODI4% [31 (22-36) vs. 14 (7-20) events/h, P = 0.002]. No significant changes occurred in the OAI or hypopnoea index. Two adverse events occurred (lead thrombus and episode of ventricular tachycardia), though neither was directly related to phrenic nerve stimulation therapy. CONCLUSION Unilateral transvenous phrenic nerve stimulation significantly reduces episodes of CSA and restores a more natural breathing pattern in patients with heart failure. This approach may represent a novel therapy for CSA and warrants further study.

The effect of hormone replacement therapy on arterial blood pressure and vascular compliance in postmenopausal women with arterial hypertension.

Arterial pathology is a major contributor to cardiovascular disease, morbidity and mortality. Women are at higher risk of cardiovascular disease after menopause. Arterial stiffness determined by pulse wave velocity, increases with age both in men and women, whereas arterial compliance in premenopausal women is greater than in men of similar age. This difference is lost in the postmenopausal years, with evidence of rapid decline in arterial compliance in the perimenopausal period. Loss of hormonal modulation is a likely explanation for reduced arterial compliance in postmenopausal women. Long-term treatment with hormone replacement therapy (HRT) may be expected to partially reverse the increase in arterial stiffness. The aim of the study was to analyse the effect of HRT on blood pressure and arterial compliance in postmenopausal women with arterial hypertension receiving hypotensive drugs. The results in the present study of postmenopausal women with mild to moderate arterial hypertension receiving HRT showed only a transient tendency towards lower blood pressure. In our study HRT was found to improve arterial compliance at 3 months after HRT, and the effect was maintained throughout 12 months. The increased arterial compliance in women receiving HRT was independent of blood pressure. In parallel with decreasing pulse wave velocity women receiving HRT had lower total and low-density lipoprotein cholesterol. The conclusions were that after 1 year HRT in postmenopausal women with arterial hypertension improves circadian blood pressure pattern, but it does not affect significantly blood pressure values and variability. The present study also shows that HRT significantly inhibits age-related rigidity of large arteries.

Eligibility for Renal Denervation: Experience at 11 European Expert Centers

Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure–lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center’s criteria was 42.5% (95% confidence interval, 38.0%–47.0%) and 39.7% (36.2%–43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered.Based on the SYMPLICITY studies and CE (Conformite Europeenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure–lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center’s criteria was 42.5% (95% confidence interval, 38.0%–47.0%) and 39.7% (36.2%–43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered. # Novelty and Significance {#article-title-32}

Aortic pulse wave velocity in young normotensives with a family history of hypertension.

OBJECTIVE To assess the effect of selected clinical and biochemical parameters, with particular consideration of familial hypertension, on the pulse wave velocity (PWV) in young normotensives. SUBJECTS AND METHODS Seventy voluntary students were enrolled (mean age 22.3+/-2.1 years), 39 men and 31 women, with normal blood pressure. A history was obtained with respect to diabetes mellitus, ischaemic heart disease, lipid disorders and arterial hypertension in the family. The subjects were subdivided into two groups: those with (n = 33) and without (n = 37) a family history of arterial hypertension, and blood pressure and heart rate were measured three times and total cholesterol and its subfractions determined in plasma. The carotid to femoral PWV was measured using an automatic computerized recorder and analysed by the Complior program. RESULTS The subjects with a family history of arterial hypertension had higher blood pressure levels (systolic and diastolic blood pressure, pulse pressure and mean arterial pressure), as well as mean body mass index and low-density lipoprotein (LDL) cholesterol. The PWV in this group did not differ from that in the subjects without a family history of arterial hypertension (9.69+/-2.8 versus 9.32+/-2.0). However, the PWV was significantly higher in males than females (10.62+/-2.2 versus 7.86+/-1.13, P < 0.0001) and there was a significant positive correlation between male gender and PWV. CONCLUSIONS Familial arterial hypertension does not significantly affect aortic stiffness in terms of PWV. Male gender in this population of young healthy subjects is one of the most important factors associated with central arterial stiffness.

QT dispersion and hypertensive heart disease in the elderly.

Aim To determine the predictors and risk of increased QT dispersion in the elderly hypertensive patients. Methods A 12-lead electrocardiogram (ECG), M-mode echocardiography and ambulatory blood pressure as well as Holter monitoring were performed for 67 patients over 60 years of age with essential hypertension (I and II° WHO). The presence of ischaemic changes on ECG was evaluated based on the Minnesota Code. QT intervals were corrected with Bazett0s formulae and QT dispersion was determined as the difference between maximal and minimal QTc intervals. Interventricular septal thickness (IVSTd), left ventricular internal diameter (LVDd) and posterior wall thickness (PWTd) were measured and left ventricular mass index (LVMI) was calculated. Subjects were divided according to the median of QTc dispersion (0.10 s). The differences between groups were assessed using chi-squared and Students t-test. Results Subjects with increased QTc dispersion did not differ from those with low QTc dispersion when age, gender and body mass index were analysed. Similarly, the average systolic blood pressure, diastolic blood pressure and blood pressure variability were comparable in both groups. The mean QTc interval was similar in both groups. In patients with increased QT dispersion, left ventricular hypertrophy (LVH) and ischaemic changes on ECG were more frequently recognized (respectively 41.2 versus 18.2%, P < 0.001; 47.1 versus 21.2%, P < 0.05). Moreover, these subjects presented a significantly greater number of premature ventricular beats (317.1 ± 665.6 versus 64.88 6 188.6, P < 0.05) and higher classes of Lowns arrhrythmia scale (classes III-IV, 23.35% versus 9.1%). LVMI was insignificantly higher in the group with greater QTc dispersion (165.82 ± 54.5 versus 145.07 ± 36.47 g/m2). Other echocardiographic indices of LVH were similar in both groups. On the other hand, the analysis of regression indicated positive correlation between the dispersion of QTc interval and thickness of left ventricle walls (for IVSd – r = 0.37; for PWd – r = 0.31), relative wall thickness (r = 0.28) and LVMI (r = 0.28). Conclusions QTc dispersion is increased in the elderly hypertensive individuals, with the presence of LVH and myocardial ischaemia on ECG. These patients are more likely to demonstrate severe ventricular dysrhythmias.

Left ventricular lead implantation at a phrenic stimulation site is safe and effective.

AIMS Phrenic stimulation (PS) is a major limiting factor for both left ventricular (LV) lead placement and cardiac resynchronization therapy (CRT) delivery. We have developed a protocol allowing for LV lead implantation at a PS site based on specific criteria regarding phrenic and LV acute capture thresholds. The present study examined long-term outcomes in patients treated using this protocol. METHODS AND RESULTS A total of 211 consecutive patients underwent CRT device implantation. The procedure was successful in 201 patients. Leads were implanted at a PS site in 27 patients (PS patients) and a non-PS site in 174 patients (non-PS patients). Left ventricular leads were placed at a PS site only on the following conditions: no PS at ≤3.5 V/0.5 ms, LV threshold ≤1.5 V, and a PS/LV threshold ratio >4. The mean PS threshold decreased (5.1 ± 1.6 vs. 2.8 ± 1.6 V, P < 0.001) and the mean LV threshold remained stable (1.0 ± 0.7 vs. 0.9 ± 0.8 V, P = 0.6) in PS patients over the 16 ± 9 month follow-up. Only one PS patient experienced non-reprogrammable PS and required a re-operation. Seven PS patients required very low LV channel output programming without the usual safety margin of twice the LV threshold amplitude or three times the pulse width. However, 100% LV capture was shown in those patients during daily activity. Non-reprogrammable PS occurred in 2 of the 174 non-PS patients. CONCLUSION Our strategy for LV lead implantation at a PS site was found to result in long-term safe and effective outcomes.

Ambulatory blood pressure, left ventricular mass and vascular phenotypes in relation to the endothelial nitric oxide synthase gene Glu298Asp and intron 4 polymorphisms in a population-based family study

Reduced nitric oxide production is associated with pathological changes in the cardiovascular system. In a study of randomly chosen families, we analysed the relationship between two polymorphisms (Glu298Asp and intron 4) of the endothelial nitric oxide synthase (eNOS) and ambulatory blood pressure (ABP), left ventricular mass index (LVMI) and vascular phenotypes. The study population consisted of 127 parents and 167 offspring. All subjects underwent 24 h ABP monitoring using a SpaceLabs 90207 device. 2D and M-mode echocardiograms were obtained. Pulse wave velocity between the common carotid and femoral artery was measured with the Complior® device, and the carotid intima-media thickness (IMT) was assessed by ultrasound. For statistical analysis, covariables and correlations between relatives were taken into account. The frequency of genotypes was as follows: for Glu298Asp: 55.1%—Glu/Glu, 40.1%—Glu/Asp and 4.8%—Asp/Asp; for intron 4: 65.0%—4 b/b, 33.3%—4 b/a and 1.7%—4 a/a, being in Hardy–Weinberg equilibrium (P⩾0.29). There was no relationship between the eNOS gene polymorphisms and ABP or LVMI either in parents or their offspring. Among parents, carriers of the 298Asp allele had higher IMT values as compared with Glu/Glu homozygotes (0.94 vs 0.70 mm; P=0.007). Among offspring, there was a similar tendency (0.60 vs 0.53 mm; P=0.10), which was confirmed by transmission disequilibrium tests for quantitative variables (P⩾0.07). Our findings indicate that the Glu298Asp polymorphism of eNOS identifies patients with larger carotid IMT, also in younger subjects.Journal of Human Hypertension advance online publication, 03 March 2005; doi:10.1038/sj.jhh.1001837

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

BACKGROUND The 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. METHODS We 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. RESULTS In 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). CONCLUSIONS In 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.

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.