[Environment and cardiovascular health: causes, consequences and opportunities in prevention and treatment]. / Medio ambiente y salud cardiovascular: causas, consecuencias y oportunidades en prevención y tratamiento.

The environment is a strong determinant of cardiovascular health. Environmental cardiology studies the contribution of environmental exposures with the aim of minimizing the harmful influences of pollution and promoting cardiovascular health through specific preventive or therapeutic strategies. The present review focuses on particulate matter and metals, which are the pollutants with the strongest level of scientific evidence, and includes possible interventions. Legislation, mitigation and control of pollutants in air, water and food, as well as environmental policies for heart-healthy spaces, are key measures for cardiovascular health. Individual strategies include the chelation of divalent metals such as lead and cadmium, metals that can only be removed from the body via chelation. The TACT (Trial to Assess Chelation Therapy, NCT00044213) clinical trial demonstrated cardiovascular benefit in patients with a previous myocardial infarction, especially in those with diabetes. Currently, the TACT2 trial (NCT02733185) is replicating the TACT results in people with diabetes. Data from the United States and Argentina have also shown the potential usefulness of chelation in severe peripheral arterial disease. More research and action in environmental cardiology could substantially help to improve the prevention and treatment of cardiovascular disease.

Environment and cardiovascular health: causes, consequences and opportunities in prevention and treatment.

The environment is a strong determinant of cardiovascular health. Environmental cardiology studies the contribution of environmental exposures with the aim of minimizing the harmful influences of pollution and promoting cardiovascular health through specific preventive or therapeutic strategies. The present review focuses on particulate matter and metals, which are the pollutants with the strongest level of scientific evidence, and includes possible interventions. Legislation, mitigation and control of pollutants in air, water and food, as well as environmental policies for heart-healthy spaces, are key measures for cardiovascular health. Individual strategies include the chelation of divalent metals such as lead and cadmium, metals that can only be removed from the body via chelation. The TACT (Trial to Assess Chelation Therapy, NCT00044213) clinical trial demonstrated cardiovascular benefit in patients with a previous myocardial infarction, especially in those with diabetes. Currently, the TACT2 trial (NCT02733185) is replicating the TACT results in people with diabetes. Data from the United States and Argentina have also shown the potential usefulness of chelation in severe peripheral arterial disease. More research and action in environmental cardiology could substantially help to improve the prevention and treatment of cardiovascular disease.

Implications of Iron Deficiency in STEMI Patients and in a Murine Model of Myocardial Infarction.

In patients with a first anterior ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, iron deficiency (ID) was associated with larger infarcts, more extensive microvascular obstruction, and higher frequency of adverse left ventricular remodeling as assessed by cardiac magnetic resonance imaging. In mice, an ID diet reduced the activity of the endothelial nitric oxide synthase/soluble guanylate cyclase/protein kinase G pathway in association with oxidative/nitrosative stress and increased infarct size after transient coronary occlusion. Iron supplementation or administration of an sGC activator before ischemia prevented the effects of the ID diet in mice. Not only iron excess, but also ID, may have deleterious effects in the setting of ischemia and reperfusion.

Mapping potentials adjacent to the cavo-tricuspid isthmus ablation line during incremental pacing: A feasible and highly accurate maneuver to confirm complete CTI conduction block.

BACKGROUND: The diagnostic accuracy of incremental atrial pacing (IP) to determine complete cavo-tricuspid isthmus (CTI) block during typical atrial flutter (AFL) ablation is limited by both an extensive/nonlinear ablation and/or the presence of intra-atrial conduction delay elsewhere in the right atrium. We examined the diagnostic performance of an IP variant based on the assessment of the atrial potentials adjacent to the ablation line which aims at overcoming both limitations. METHODS: From a prospective population of 108 consecutive patients, 15 were excluded due to observation of inconclusive CTI ablation potentials precluding for a straight comparison between the IP maneuver and its variant. In the remaining 93, IP was performed from the low lateral right atrium and the coronary sinus ostium, with the ablation catheter positioned both at the CTI line and adjacent (<5 mm) to its septal and lateral aspect. The IP variant consisted of measuring the interval between the two atrial electrograms situated on the same side of the ablation line, opposite to the pacing site, a ≤10 ms increase indicating complete CTI block. RESULTS: The IP maneuver and its variant were consistent with complete CTI block in 82/93 (88%) and 87/93 (93%) patients, respectively. Four patients had AFL recurrence during follow-up: 2/4 and 4/4 had been adequately classified as incomplete block by the IP maneuver and its variant, respectively. Twenty-three patients (24%) had significant intra-atrial conduction delay elsewhere in the right atrium. The IP maneuver and its variant were suggestive of an incomplete CTI block in 11/23 and 4/23 in this setting (P = .028), with the later best predicting subsequent AFL relapses (2/12 vs 2/4, P = .01). CONCLUSIONS: The IP variant, which was designed to overcome the limitations of the conventional IP maneuver, accurately distinguishes complete from incomplete CTI block and helps to predict AFL recurrences after ablation.

Burning the Gap: Electrical and Anatomical Basis of the Incremental Pacing Maneuver for Cavotricuspid Isthmus Block Assessment.

INTRODUCTION: The incremental pacing (IP) maneuver is a highly specific technique that improves the ability to confirm complete CTI conduction block during typical atrial flutter (AFL) ablation, and reduces long-term AFL recurrences. The purpose of this study is to assess the performance of new catheters equipped with additional high precision bipoles (AHPB) to allow the visualization of the cavotricuspid isthmus (CTI) conduction gap and to compare them with the IP maneuver. METHODS AND RESULTS: Twenty consecutive patients undergoing catheter ablation of the CTI for AFL were included. The IP maneuver confirmed functional versus complete CTI block. Local electrogram analysis using AHPB was then used to assess the presence or absence of gaps across the CTI line. Mean age was 67 years and 80% were male. At the end of the procedure CTI block was achieved in all patients. A transient stage of functional CTI block was observed in 40%. In all cases a continuous fragmented electrogram was present between the double potentials in the CTI in the AHPB channels. In contrast, no electrogram was observed between the CTI double potentials in any of the 20 patients once complete block was confirmed by the IP maneuver. When both techniques were compared a significant association and correlation were observed (chi-square <0.01, Spearman's rho = 1, P < 0.01). CONCLUSION: Catheters equipped with AHPB can aid in the assessment of complete CTI block during AFL ablation procedures by detecting conduction gaps that correlate with incomplete functional block diagnosed by the IP maneuver.

Incremental His-to-coronary sinus maneuver: a nonlocal electrogram-based technique to assess complete cavotricuspid isthmus block during typical flutter ablation.

BACKGROUND: Achievement of complete cavotricuspid isthmus (CTI) conduction block reduces typical atrial flutter recurrences after ablation. The lack of increase in the His-to-coronary sinus ostium atrial interval during incremental pacing (IP) from the low lateral right atrium may distinguish slow conduction from complete CTI conduction block. METHODS AND RESULTS: Sixty-six consecutive patients (age, 65±13 years; 18% female) were prospectively included. A <10 ms increase in the His-to-coronary sinus ostium atrial timing during low lateral right atrium IP at cycle length of 600 ms through 300 ms was compared with the previously reported IP maneuver for the confirmation of complete CTI block. On the basis of the IP maneuver, complete CTI block (phase 2) was achieved in 59 patients, in 13 of whom an intermediate phase of functional CTI block (phase 1) was observed. In the remaining 7 patients, the IP maneuver did not allow for assessment of complete CTI block because of the presence of inconclusive potentials in the CTI ablation line. As compared with the IP maneuver, the incremental His-to-coronary sinus ostium maneuver was consistent with functional CTI block during phase 1 in all cases and conclusive of complete CTI block in 98% of cases during phase 2. CONCLUSIONS: The incremental His-to-coronary sinus ostium maneuver is analogous to the IP maneuver in distinguishing complete CTI block from persistent CTI conduction. This maneuver may provide confirmation of CTI block in those patients in whom assessment of local electrogram-based criteria is not feasible because of inconclusive potentials in the CTI ablation line.

T-type calcium current contributes to escape automaticity and governs the occurrence of lethal arrhythmias after atrioventricular block in mice.

BACKGROUND: When complete atrioventricular block (AVB) occurs, infranodal escape rhythms are essential to prevent bradycardic death. The role of T-type Ca(2+) channels in pacemaking outside the sinus node is unknown. We investigated the role of T-type Ca(2+) channels in escape rhythms and bradycardia-related ventricular tachyarrhythmias after AVB in mice. METHODS AND RESULTS: Adult male mice lacking the main T-type Ca(2+) channel subunit Cav3.1 (Cav3.1(-/-)) and wild-type (WT) controls implanted with ECG telemetry devices underwent radiofrequency atrioventricular node ablation to produce AVB. Before ablation, Cav3.1(-/-) mice showed sinus bradycardia (mean±SEM; RR intervals, 148±3 versus 128±2 ms WT; P<0.001). Immediately after AVB, Cav3.1(-/-) mice had slower escape rhythms (RR intervals, 650±75 versus 402±26 ms in WT; P<0.01) but a preserved heart-rate response to isoproterenol. Over the next 24 hours, mortality was markedly greater in Cav3.1(-/-) mice (19/31; 61%) versus WT (8/26; 31%; P<0.05), and Torsades de Pointes occurred more frequently (73% Cav3.1(-/-) versus 35% WT; P<0.05). Escape rhythms improved in both groups during the next 4 weeks but remained significantly slower in Cav3.1(-/-). At 4 weeks after AVB, ventricular tachycardia was more frequent in Cav3.1(-/-) than in WT mice (746±116 versus 214±78 episodes/24 hours; P<0.01). Ventricular function remodeling was similar in Cav3.1(-/-) and WT, except for smaller post-AVB fractional-shortening increase in Cav3.1(-/-). Expression changes were seen post-AVB for a variety of genes; these tended to be greater in Cav3.1(-/-) mice, and overexpression of fetal and profibrotic genes occurred only in Cav3.1(-/-). CONCLUSIONS: This study suggests that T-type Ca(2+) channels play an important role in infranodal escape automaticity. Loss of T-type Ca(2+) channels worsens bradycardia-related mortality, increases bradycardia-associated adverse remodeling, and enhances the risk of malignant ventricular tachyarrhythmias complicating AVB.

HAK transporters from Physcomitrella patens and Yarrowia lipolytica mediate sodium uptake.

The widespread presence of Na(+)-specific uptake systems across plants and fungi is a controversial topic. In this study, we identify two HAK genes, one in the moss Physcomitrella patens and the other in the yeast Yarrowia lipolytica, that encode Na(+)-specific transporters. Because HAK genes are numerous in plants and are duplicated in many fungi, our findings suggest that some HAK genes encode Na(+) transporters and that Na(+) might play physiological roles in plants and fungi more extensively than is currently thought.

The SOS1 transporter of Physcomitrella patens mediates sodium efflux in planta.

• SOS1 is an Na(+)/H(+) antiporter that plays a central role in Na(+) tolerance in land plants. SOS1 mediation of Na(+) efflux has been studied in plasma-membrane vesicles and deduced from the SOS1 suppression of the Na(+) sensitivity of yeast mutants defective in Na(+) -efflux. However, SOS1-mediated Na(+) efflux has not been characterized in either plant or yeast cells. Here, we use Physcomitrella patens to investigate the function of SOS1 in planta. • In P. patens, a nonvascular plant in which the study of ion cellular fluxes is technically simple, the existence of two SOS1 genes suggests that the Na(+) efflux remaining after the deletion of the ENA1 ATPase is mediated by a SOS1 system. Therefore, we cloned the P. patens SOS1 and SOS1B genes (PpSOS1 and PpSOS1B, respectively) and complementary DNAs, and constructed the PpΔsos1 and PpΔena1/PpΔsos1 deletion lines by gene targeting. • Comparison of wild-type, and PpΔsos1 and PpΔena1/PpΔsos1 mutant lines revealed that PpSOS1 is crucial for Na(+) efflux and that the PpΔsos1 line, and especially the PpΔena1/PpΔsos1 lines, showed excessive Na(+) accumulation and Na(+)-triggered cell death. The PpΔsos1 and PpΔena1/PpΔsos1 lines showed impaired high-affinity K(+) uptake. • Our data support the hypothesis that PpSOS1 mediates cellular Na(+) efflux and that PpSOS1 enhances K(+) uptake by an indirect effect.

Characterization of focal right atrial appendage tachycardia.

AIMS: Though right atrial appendage tachycardia (RAAT) has been described, no studies to date have focused on its clinical characterization. The aim of the present study was to analyze its clinical, electrocardiographic (ECG), and electrophysiologic (EP) characteristics and the results of radiofrequency ablation (RFA) in RAAT. METHODS AND RESULTS: Out of 186 consecutive patients undergoing RFA for AT, 15 (8%) had focal RAAT. Mapping was performed using conventional catheters or a 3D electroanatomic mapping system. Patients with RAAT were more likely to be male (66 vs. 38%; P= 0.013) and younger (32 +/- 12.6 vs. 55 +/- 13.2 years; P < 0.001) than patients with AT originating elsewhere. They were also more likely to have dyspnea (27 vs. 7.6%; P = 0.03), incessant tachycardia (53 vs. 16%; P < 0.001), and left ventricular systolic dysfunction (27 vs. 5%; P = 0.018). RFA was effective in all patients (100 vs. 75%; P = 0.022) and no recurrences (0 vs. 8%; P = 0.31) were observed during a mean follow-up of 37 +/- 36 months. A specific ECG pattern was identified, consisting of negative P-waves in leads V1-V2 and a transition to positivity in the rest of the precordial leads. This ECG pattern correctly identified RAAT with a sensitivity of 100%, a specificity of 98%, a positive predictive value of 88%, and a negative predictive value of 100%. CONCLUSION: Right atrial appendage tachycardia is more prevalent in young male patients and is commonly associated with tachycardiomyopathy. RFA is effective over long-term follow-up. A characteristic ECG pattern identifies RAAT with a very high sensitivity and specificity.

Cloning of two SOS1 transporters from the seagrass Cymodocea nodosa. SOS1 transporters from Cymodocea and Arabidopsis mediate potassium uptake in bacteria.

Two cDNAs isolated from Cymodocea nodosa, CnSOS1A, and CnSOSIB encode proteins with high-sequence similarities to SOS1 plant transporters. CnSOS1A expressed in a yeast Na+-efflux mutant under the control of a constitutive expression promoter mimicked AtSOS1 from Arabidopsis; the wild type cDNA did not improve the growth of the recipient strain in the presence of Na+, but a cDNA mutant that expresses a truncated protein suppressed the defect of the yeast mutant. In similar experiments, CnSOS1B was not effective. Conditional expression, under the control of an arabinose responsive promoter, of the CnSOSIA and CnSOS1B cDNAs in an Escherichia coli mutant defective in Na+ efflux was toxic, and functional analyses were inconclusive. The same constructs transformed into an E. coli K+-uptake mutant revealed that CnSOS1A was also toxic, but that it slightly suppressed defective growth at low K+. Truncation in the C-terminal hydrophilic tail of CnSOS1A relieved the toxicity and proved that CnSOS1A was an excellent low-affinity K+ and Rb+ transporter. CnSOS1B mediated a transient, extremely rapid K+ or Rb+ influx. Similar tests with AtSOS1 revealed that it was not toxic and that the whole protein exhibited excellent K+ and Rb+ uptake characteristics in bacteria.

Sodium, potassium-atpases in algae and oomycetes.

We have investigated the presence of K(+)-transporting ATPases that belong to the phylogenetic group of animal Na(+),K(+)-ATPases in the Pythium aphanidermatum Stramenopile oomycete, the Porphyra yezoensis red alga, and the Udotea petiolata green alga, by molecular cloning and expression in heterologous systems. PCR amplification and search in EST databases allowed one gene to be identified in each species that could encode ATPases of this type. Phylogenetic analysis of the sequences of these ATPases revealed that they cluster with ATPases of animal origin, and that the algal ATPases are closer to animal ATPases than the oomycete ATPase is. The P. yezoensis and P. aphanidermatum ATPases were functionally expressed in Saccharomyces cerevisiae and Escherichia coli alkali cation transport mutants. The aforementioned cloning and complementary searches in silicio for H(+)- and Na(+),K(+)-ATPases revealed a great diversity of strategies for plasma membrane energization in eukaryotic cells different from typical animal, plant, and fungal cells.

Molecular cloning and functional expression in bacteria of the potassium transporters CnHAK1 and CnHAK2 of the seagrass Cymodocea nodosa.

The cDNAs CnHAK1 and CnHAK2, encoding K+ transporters, were amplified from the leaves of the seagrass Cymodocea nodosa. None of these transporters suppressed the K+ deficiency of a Saccharomyces cerevisiae mutant, but both suppressed the equivalent defect of an Escherichia coli mutant. Overexpression of the transporter CnHAKI, but not CnHAK2, mediated very rapid K+ or Rb+ influxes in the E. coli mutant. The concentration dependence of these influxes demonstrated that CnHAK1 is a low-affinity K+ transporter, which does not discriminate between K+ and Rb+. CnHAK1 expressed in E. coli worked in reverse when the external K+ concentrations were low, and we established the condition of a simple functional test of K+ loss for transporters of the Kup-HAK family. In comparison with its homologue barley transporter HvHAK2, CnHAKI was insensitive to Na+.