Strategies for repeat ablation for atrial fibrillation: A multicentre comparison of nonpulmonary vein versus pulmonary vein target ablation.

INTRODUCTION: Approximately 18% of patients with atrial fibrillation (AF) undergo a repeat ablation within 12 months after their index ablation. Despite the high prevalence, comparative studies on nonpulmonary vein (PV) target strategies in repeat AF ablation are scarce. Here, we describe 12 months efficacy of non-PV and PV target ablations as a repeat ablation strategy. METHODS: A multicentre retrospective, descriptive study was conducted with data of 280 patients who underwent repeat AF ablation. The ablation strategy for repeat ablation was at the operators' discretion. Non-PV target ablation (n = 140) included PV reisolation, posterior wall isolation, mitral line, roofline, and/or complex fractionated atrial electrogram ablation. PV target ablation (n = 140), included reisolation and/or wide atrium circumferential ablation. Patients' demographics and rhythm outcomes during 12 months follow-up were analyzed. RESULTS: At 12 months, more atrial tachyarrhythmias were observed in the non-PV target group (48.6%) compared to the PV target group (29.3%, p = .001). Similarly, a significantly higher AF and atrial tachycardia (AT) recurrence rate was observed after non-PV target ablation compared to PV target ablation (36.4% vs. 22.1% and 22.9% vs. 10.7%). After adjustment, a significantly higher risk of AT recurrence remained in the non-PV target group. Both groups significantly de-escalated antiarrhythmic drug use; de-escalation was more profound after PV target ablation. Patients with isolated PVs during non-PV target ablation had a significantly higher risk for AF recurrence than those with reconnected PVs. CONCLUSION: Compared to PV target ablation, non-PV target repeat ablation did not improve outcomes after 12 months and was independently associated with an increased risk for AT recurrences.

[Aortic valve replacement and screening for frailty]. / Aortaklepvervanging en screening op kwetsbaarheid.

The prevalence of aortic stenosis is increasing due to aging of the general population. Transcatheter aortic valve implantation (TAVI) is an alternative for surgical aortic valve replacement (AVR) for high-risk patients. Cardiac scoring systems have been developed to predict the risk of adverse outcomes following surgery, but currently they do not include frailty parameters, and frail patients have an increased risk of adverse health outcomes. Preoperative frailty correlates with adverse outcomes, mortality and functional decline in patients undergoing TAVI; by identifying these patients it is possible to counteract symptoms of frailty by implementing tailored intervention by the geriatrician. The Comprehensive Geriatric Assessment (CGA) is a tool used to detect frailty. Based on the current literature, we highly recommend performing a CGA and a minimum of a Timed Up and Go test, a mini nutritional assessment and serum albumin measurements in patients aged > 70 years undergoing a TAVI or surgical AVR, in order to aim reducing the accompanying risks of the intervention.

Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?

BACKGROUND: Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype. METHODS: Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates. RESULTS: Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations. CONCLUSIONS: We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.

Genetic factors are relevant and independent determinants of antihypertensive drug effects in a multiracial population.

BACKGROUND: The success of antihypertensive drugs may be improved by better prediction of their efficacy in individual patients. The objective of our study was to determine whether genetic variation predicts the individual systolic blood pressure (SBP) response to antihypertensive drugs and to assess to what extent the individual treatment response could be explained by the combined effects of known demographic, environmental, and genetic factors. METHODS: A population-based, crossover, open-label randomized treatment study stratified for ethnicity in 102 mildly hypertensive patients aged 35-60 years in an outpatient hypertension clinic (the ROTATE study). Patients underwent five successive 6-week treatment episodes of single-drug treatment in a randomized order with representatives of the major antihypertensive drug classes. The primary outcome measure was the DeltaSBP after 6-week drug therapy. RESULTS: Participants (n = 97) completed 407 treatment episodes. The estimated unpredictable natural variation of SBP within individuals was 65% of the total study variance. The primary analysis model that considered the effects of environmental, demographic, and genetic factors and their interactions to SBP response to antihypertensive drugs, explained 23% of the total variance accounting for 66% of the predictable variance. Ethnicity, low sodium intake, and ADD1 614G-->T polymorphism were the only drug-related predictors. A number of genetic variants (ADD1 614G-->T, ADRB1 145A-->G, ADRB2 79C-->G, CYP11B2 -344C-->T, and SLC12A3 78G-->A) contributed significantly (9%) to the total variance of the SBP response. The contribution of each individual single-nucleotide polymorphism (SNP) ranged from 1.1 to 2.4%. CONCLUSIONS: Genetic factors are relevant and independent determinants of antihypertensive drug effects in a multiracial population.

Low creatine kinase is associated with a high population incidence of fainting.

OBJECTIVE: Vasoconstrictor capacity, skeletal muscle tone, and renal sodium retention are involved in the pathogenesis of fainting. As muscle contractility and ion transport are highly energy-demanding processes, we hypothesized that a low activity of the energy-generating enzyme creatine kinase (CK) is associated with a higher risk of fainting. The aim of this observational study was to explore the association of vasovagal syncope with low CK. METHODS: A random sample of 1,000 subjects aged 34-60 years was drawn from the general population, with 442 subjects eventually included in the study. Data on fainting history were collected with the investigators blinded to participants' CK level. We prepared this report according to the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) statement. The main outcome was the lifetime cumulative incidence of vasovagal syncope in subjects with low versus high-normal serum CK after a 3 days rest. RESULTS: The proportion of fainters within the high CK group was 29 out of 130 (22%) versus 121 out of 312 (39%) in the low CK group; a 73% greater occurrence of fainting with low CK (P = 0.0005). This finding was consistent across recurrent fainters, and in men and women. INTERPRETATION: Low CK is associated with a 73% higher incidence of fainting in a random population sample. The association is biologically plausible, as CK enhances cardiovascular and skeletal muscle contractility and salt retention. The presented data suggest that low CK activity is a potential new risk factor for vasovagal syncope.

Are RGS2 gene polymorphisms associated with high blood pressure in an ethnicity- and gender-specific manner?

BACKGROUND: Polymorphisms in the Regulator of G-protein Signaling 2 (RGS2) gene have been reported to be associated with hypertension (HT) in Japanese women and black Americans of either gender but not in white Americans or Japanese men. We have tested whether these proposed ethnicity- and gender-specific associations between RGS2 gene polymorphisms and HT can be confirmed in an independent population of male and female blacks, whites, and south Asians. METHODS: A population-based sample of 1379 black, white Dutch, and south Asian subjects from the Amsterdam area was genotyped for eight polymorphisms in the RGS2 gene. All analyses were done separately per ethnic group. The phenotype high blood pressure was defined as a dichotomous variable comparing HT vs. normotension (NT) and as a linear variable using systolic blood pressure (SBP) in a multiple regression analysis with concomitant antihypertensive medication, age and body mass index as coexplanatory variables. RESULTS: Ethnic differences in the frequency of polymorphisms and haplotypes (HAPs) derived thereof were in line with previous studies. Our data do not confirm previously reported ethnicity- or gender-specific associations regardless which phenotype definition was used. While the D allele of 1891-1892TC insertion/deletion polymorphism showed association in several groups, they differed from previously reported ones. Haplotype-phenotype analysis was not more sensitive to detect genotype-phenotype associations than individual alleles. CONCLUSIONS: Previously reported ethnicity- and gender-specific associations of RGS2 genotype and hypertensive phenotype are not robust. Nevertheless, the 1891-1892TC insertion/deletion polymorphism warrants further investigation.

Prevalence of diabetes mellitus and the performance of a risk score among Hindustani Surinamese, African Surinamese and ethnic Dutch: a cross-sectional population-based study.

BACKGROUND: While the prevalence of type 2 diabetes mellitus (DM) is high, tailored risk scores for screening among South Asian and African origin populations are lacking. The aim of this study was, first, to compare the prevalence of (known and newly detected) DM among Hindustani Surinamese, African Surinamese and ethnic Dutch (Dutch). Second, to develop a new risk score for DM. Third, to evaluate the performance of the risk score and to compare it to criteria derived from current guidelines. METHODS: We conducted a cross-sectional population based study among 336 Hindustani Surinamese, 593 African Surinamese and 486 Dutch, aged 35-60 years, in Amsterdam. Logistic regressing analyses were used to derive a risk score based on non-invasively determined characteristics. The diagnostic accuracy was assessed by the area under the Receiver-Operator Characteristic curve (AUC). RESULTS: Hindustani Surinamese had the highest prevalence of DM, followed by African Surinamese and Dutch: 16.7, 8.1, 4.2% (age 35-44) and 35.0, 19.0, 8.2% (age 45-60), respectively. The risk score included ethnicity, body mass index, waist circumference, resting heart rate, first-degree relative with DM, hypertension and history of cardiovascular disease. Selection based on age alone showed the lowest AUC: between 0.57-0.62. The AUC of our score (0.74-0.80) was higher than that of criteria from guidelines based solely on age and BMI and as high as criteria that required invasive specimen collection. CONCLUSION: In Hindustani Surinamese and African Surinamese populations, screening for DM should not be limited to those over 45 years, as is advocated in several guidelines. If selective screening is indicated, our ethnicity based risk score performs well as a screening test for DM among these groups, particularly compared to the criteria based on age and/or body mass index derived from current guidelines.

Distribution of creatine kinase in the general population: implications for statin therapy.

BACKGROUND: Eligible subjects with mildly elevated serum creatine kinase (CK) activity are often excluded before randomization in statin trials, but patients may potentially be misclassified as having hyperCKemia when inappropriate reference limits are used. Little information is usually given regarding how reference limit data were established, although evidence suggests that the variation of CK activity in the general population is wider than reflected in reference intervals in current use. METHODS: We determined reference intervals for serum CK according to National Committee on Clinical Laboratory Standards/Nordic Reference Interval Project guidelines, in a stratified random sample of the population, including 1444 individuals, aged 34 to 60 years, after 3 days of rest. Participants were mainly of white European (n = 503), South Asian (n = 292), or African descent (n = 580). RESULTS: The calculated upper reference limits (97.5th percentile) for nonblack and black women and men were 2 to 5 times higher than recommended by the assay manufacturer. Respectively 13% of the white Europeans, 23% of South Asians, and 49% of the black people had serum CK activities above the manufacturer-provided limits. CONCLUSION: The variation in CK activity within the population is wider than previously suggested in smaller, nonrandom samples, and relatively high values occur frequently in all subgroups studied after rest. Therefore, we infer that upward adjustment of the upper reference limit is necessary for all population subgroups studied. The use of appropriately established reference intervals may improve the use of statins and particularly benefit the control of dyslipidemia in those with relatively high baseline CK activity.

Creatine kinase activity is associated with blood pressure.

BACKGROUND: We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular contraction, and antagonizes nitric oxide-mediated functions. Relatively high activity of the enzyme, particularly in resistance arteries, is thought to enhance pressor responses and increase blood pressure. Tissue creatine kinase activity is reported to be high in black people, a population subgroup with greater hypertension risk; the proposed effects of high creatine kinase activity, however, are not "race dependent." We therefore assessed whether creatine kinase is associated with blood pressure in a multiethnic population. METHODS AND RESULTS: We analyzed a stratified random sample of the population of Amsterdam, The Netherlands, consisting of 1444 citizens (503 white European, 292 South Asian, 580 black, and 69 of other ethnicity) aged 34 to 60 years. We used linear regression analysis to investigate the association between blood pressure and normal serum creatine kinase after rest, as a substitute measure of tissue activity. Creatine kinase was independently associated with blood pressure, with an increase in systolic and diastolic pressure, respectively, of 8.0 (95% CI, 3.3 to 12.7) and 4.7 (95% CI, 1.9 to 7.5) mm Hg per log creatine kinase increase after adjustment for age, sex, body mass index, and ethnicity. CONCLUSIONS: Creatine kinase is associated with blood pressure. Further studies are needed to explore the nature of this association, including how variation in cardiovascular creatine kinase activity may affect pressor responses.

Lifetime cumulative incidence of syncope in the general population: a study of 549 Dutch subjects aged 35-60 years.

INTRODUCTION: There are limited and conflicting data on the lifetime cumulative incidence of syncope in the general population. The aim of our study was to determine the lifetime cumulative incidence and triggers of syncope in the general population. METHODS: Questions about syncope were added to a cross-sectional survey on cardiovascular risk factors carried out between 2001 and 2003 in 549 native Dutch respondents, aged 35-60 years. RESULTS: The lifetime cumulative incidence of syncope in our study population was 35% (95% confidence interval 31-39%). Syncope occurred more often in women than in men (41% vs 28%; P = 0.003). A peak in the incidence of syncope occurred around the age of 15 years in both men and women. The median number of episodes in persons with syncope was 2 (Inter Quartile Range 1-5). The top five most frequently mentioned triggers of syncope included warm environment, pain, insufficient food intake, seeing blood/venipuncture, and emotion. CONCLUSION: In conclusion, our study shows that the lifetime cumulative incidence of syncope in the general population is high. Females experience syncope more often than males. The majority of the syncope triggers were related to conditions that affect orthostatic blood pressure regulation and vasomotor responses.

Prevalence, awareness, treatment, and control of hypertension among Black Surinamese, South Asian Surinamese and White Dutch in Amsterdam, The Netherlands: the SUNSET study.

OBJECTIVE: To assess ethnic differences in prevalence, levels of awareness, treatment and control of hypertension among Dutch ethnic groups and to determine whether these differences are consistent with the UK findings. DESIGN: Cross-sectional survey. SETTING: South-east Amsterdam, The Netherlands. PARTICIPANTS: A random sample of 1383 non-institutional adults aged 35-60 years. Of these, 36.7% were White, 42% were Black and 21.3% were South Asian people. MAIN OUTCOME MEASURES: Prevalence of hypertension, rates of awareness, treatment, and control of hypertension. RESULTS: The Black and South Asian subjects had a higher prevalence of hypertension compared with White people. After adjustments for age, the odds ratios (95% confidence interval) for being hypertensive were 2.2 (1.4-3.4; P < 0.0001) and 3.8 (2.6-5.7; P < 0.0001) for Black men and women, respectively, and 1.7 (1.0-2.6; P = 0.039) and 2.8 (1.8-4.5; P < 0.0001) for South Asian men and women, compared with White people. There were no differences in awareness and pharmacological treatment of hypertension between the groups. However, Black hypertensive men 0.3 (0.1-0.7; P < 0.01) and women 0.5 (0.3-0.9; P < 0.05) were less likely to have their blood pressure adequately controlled compared with White people. CONCLUSION: The higher prevalence of hypertension found among Black and South Asian people in The Netherlands is consistent with the UK studies. However, the lower control rates and the similar levels of awareness and treatment of hypertension in Black Surinamese contrast with the higher rates reported in African Caribbeans in the UK. The rates for the South Asians in The Netherlands were relatively favourable compared to similar South Asian groups in the UK. These findings underscore the urgent need to develop strategies aimed at improving the prevention and control of hypertension, especially among Black people, in The Netherlands.

Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension.

Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function. Recently, the biological clock was shown to be involved in autonomic cardiovascular regulation. Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension. We conducted a randomized, double-blind, placebo-controlled, crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute (single) and repeated (daily for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg, respectively. The treatment did not affect heart rate. The day-night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15% and 25%, respectively. A single dose of melatonin had no effect on blood pressure. Repeated (but not acute) melatonin also improved sleep. Improvements in blood pressure and sleep were statistically unrelated. In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension.