Reducing Cardiovascular Mortality Through Prevention and Management of Raised Blood Pressure: A World Heart Federation Roadmap.

Prospective epidemiological data have shown that blood pressure has a graded, continuous adverse effect on the risk of various forms of CVD (including stroke, myocardial infarction, heart failure, peripheral arterial disease and end-stage renal disease). 'Raised blood pressure' is frequently considered to be any systolic blood pressure greater than 115 mmHg. It accounts for 45% of all heart disease deaths and 51% of all stroke-related deaths [1], which together are the biggest causes of morbidity and mortality worldwide [2,3,4]. Annually, there are >17 million deaths due to CVD worldwide, of which 9.4 million are attributable to complications of raised blood pressure. This highlights the importance of both high-risk and population-based strategies in blood pressure management and control.

β-Adrenergic modulation of skeletal muscle contraction: key role of excitation-contraction coupling.

Our aim is to describe the acute effects of catecholamines/β-adrenergic agonists on contraction of non-fatigued skeletal muscle in animals and humans, and explain the mechanisms involved. Adrenaline/β-agonists (0.1-30 μm) generally augment peak force across animal species (positive inotropic effect) and abbreviate relaxation of slow-twitch muscles (positive lusitropic effect). A peak force reduction also occurs in slow-twitch muscles in some conditions. β2 -Adrenoceptor stimulation activates distinct cyclic AMP-dependent protein kinases to phosphorylate multiple target proteins. β-Agonists modulate sarcolemmal processes (increased resting membrane potential and action potential amplitude) via enhanced Na(+) -K(+) pump and Na(+) -K(+) -2Cl(-) cotransporter function, but this does not increase force. Myofibrillar Ca(2+) sensitivity and maximum Ca(2+) -activated force are unchanged. All force potentiation involves amplified myoplasmic Ca(2+) transients consequent to increased Ca(2+) release from sarcoplasmic reticulum (SR). This unequivocally requires phosphorylation of SR Ca(2+) release channels/ryanodine receptors (RyR1) which sensitize the Ca(2+) -induced Ca(2+) release mechanism. Enhanced trans-sarcolemmal Ca(2+) influx through phosphorylated voltage-activated Ca(2+) channels contributes to force potentiation in diaphragm and amphibian muscle, but not mammalian limb muscle. Phosphorylation of phospholamban increases SR Ca(2+) pump activity in slow-twitch fibres but does not augment force; this process accelerates relaxation and may depress force. Greater Ca(2+) loading of SR may assist force potentiation in fast-twitch muscle. Some human studies show no significant force potentiation which appears to be related to the β-agonist concentration used. Indeed high-dose β-agonists (∼0.1 μm) enhance SR Ca(2+) -release rates, maximum voluntary contraction strength and peak Wingate power in trained humans. The combined findings can explain how adrenaline/β-agonists influence muscle performance during exercise/stress in humans.

Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium.

BACKGROUND: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. METHODS AND RESULTS: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. CONCLUSIONS: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

Right heart ischemia in cases of sepsis.

Data from the literature suggest that cases of sepsis complicated by right ventricular (RV) dysfunction have poorer prognosis. In these cases progressive hypoperfusion associated to increasing, injury-related, pulmonary vascular resistance account for RV ischemia. In the present analysis, we wanted to evaluate whether prevalent RV cardiac ischemic damage could be detected in a series of fatal sepsis cases. We retrospectively investigated 20 cases of sepsis that underwent forensic autopsy (study group-11♀, 9♂, mean age 57 years) and compared them to a group of 20 cases of hanging (hanging group-4 ♀, 16 ♂, mean age 44 years) as well as to a group of 20 cases of myocardial infarction (MI group-9 ♀, 11 ♂, mean age 65 years), as examples of cardiac damage due to global hypoxia during agony and ischemic damage, respectively. We performed immunohistochemistry with the antibodies anti-fibronectin and C5b-9. The reactions were semiquantitively classified and the groups were compared. In 30% of the cases of sepsis prevalent RV ischemic damage could be detected with the antibody anti-fibronectin. This expression was significantly different from that observed in cases of MI (p=0.028) and hanging (p<0.001). Our study showed that, in cases of fatal sepsis, prevalent RV ischemic damage occurred in a substantial minority of cases.

Typology of "Fatigue" by Heart Rate Variability Analysis in Elite Nordic-skiers.

This study investigated changes in heart rate variability (HRV) in elite Nordic-skiers to characterize different types of "fatigue" in 27 men and 30 women surveyed from 2004 to 2008. R-R intervals were recorded at rest during 8 min supine (SU) followed by 7 min standing (ST). HRV parameters analysed were powers of low (LF), high (HF) frequencies, (LF+HF) (ms(2)) and heart rate (HR, bpm). In the 1 063 HRV tests performed, 172 corresponded to a "fatigue" state and the first were considered for analysis. 4 types of "fatigue" (F) were identified: 1. F(HF(-)LF(-))SU_ST for 42 tests: decrease in LFSU (- 46%), HFSU (- 70%), LFST (- 43%), HFST (- 53%) and increase in HRSU (+ 15%), HRST (+ 14%). 2. F(LF(+) SULF(-) ST) for 8 tests: increase in LFSU (+ 190%) decrease in LFST (- 84%) and increase in HRST (+ 21%). 3. F(HF(-) SUHF(+) ST) for 6 tests: decrease in HFSU (- 72%) and increase in HFST (+ 501%). 4. F(HF(+) SU) for only 1 test with an increase in HFSU (+ 2161%) and decrease in HRSU (- 15%). Supine and standing HRV patterns were independently modified by "fatigue". 4 "fatigue"-shifted HRV patterns were statistically sorted according to differently paired changes in the 2 postures. This characterization might be useful for further understanding autonomic rearrangements in different "fatigue" conditions.

Association between parental history and genetic risk scores for coronary heart disease prediction: The population-based CoLaus study.

BACKGROUND AND AIMS: Parental history (PH) and genetic risk scores (GRSs) are separately associated with coronary heart disease (CHD), but evidence regarding their combined effects is lacking. We aimed to evaluate the joint associations and predictive ability of PH and GRSs for incident CHD. METHODS: Data for 4283 Caucasians were obtained from the population-based CoLaus Study, over median follow-up time of 5.6 years. CHD was defined as incident myocardial infarction, angina, percutaneous coronary revascularization or bypass grafting. Single nucleotide polymorphisms for CHD identified by genome-wide association studies were used to construct unweighted and weighted versions of three GRSs, comprising of 38, 53 and 153 SNPs respectively. RESULTS: PH was associated with higher values of all weighted GRSs. After adjustment for age, sex, smoking, diabetes, systolic blood pressure, low and high density lipoprotein cholesterol, PH was significantly associated with CHD [HR 2.61, 95% CI (1.47-4.66)] and further adjustment for GRSs did not change this estimate. Similarly, one standard deviation change of the weighted 153-SNPs GRS was significantly associated with CHD [HR 1.50, 95% CI (1.26-1.80)] and remained so, after further adjustment for PH. The weighted, 153-SNPs GRS, but not PH, modestly improved discrimination [(C-index improvement, 0.016), p = 0.048] and reclassification [(NRI improvement, 8.6%), p = 0.027] beyond cardiovascular risk factors. After including both the GRS and PH, model performance improved further [(C-index improvement, 0.022), p = 0.006]. CONCLUSION: After adjustment for cardiovascular risk factors, PH and a weighted, polygenic GRS were jointly associated with CHD and provided additive information for coronary events prediction.

New Insights in the Diagnosis and Treatment of Heart Failure.

Cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndrome are leading to an increasing number of "survivors" who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The aim of this review is to evaluate the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists.

Surgical treatment for heart myxomas.

According to unselected autopsy data, primary cardiac tumours are a rare entity. About 80% of the tumours are benign and nearly half of these are myxomas. In clinical practice, when diagnosis of this pathological entity is ascertained, decision for surgical treatment is made in order to prevent thromboembolism and obstruction of the valvular apparatus. Surgical resection including total tumour removal is accompanied by low perioperative mortality. The recidive rate is low in sporadic cases. However, in familial syndrome groups, such as the Swiss-Carney syndrome, the recurrence rate is higher.

Procedural Results and Clinical Outcomes of Transcatheter Aortic Valve Implantation in Switzerland: An Observational Cohort Study of Sapien 3 Versus Sapien XT Transcatheter Heart Valves.

BACKGROUND: New generation transcatheter heart valves (THV) may improve clinical outcomes of transcatheter aortic valve implantation. METHODS AND RESULTS: In a nationwide, prospective, multicenter cohort study (Swiss Transcatheter Aortic Valve Implantation Registry, NCT01368250), outcomes of consecutive transfemoral transcatheter aortic valve implantation patients treated with the Sapien 3 THV (S3) versus the Sapien XT THV (XT) were investigated. An overall of 153 consecutive S3 patients were compared with 445 consecutive XT patients. Postprocedural mean transprosthetic gradient (6.5±3.0 versus 7.8±6.3 mm Hg, P=0.17) did not differ between S3 and XT patients, respectively. The rate of more than mild paravalvular regurgitation (1.3% versus 5.3%, P=0.04) and of vascular (5.3% versus 16.9%, P<0.01) complications were significantly lower in S3 patients. A higher rate of new permanent pacemaker implantations was observed in patients receiving the S3 valve (17.0% versus 11.0%, P=0.01). There were no significant differences for disabling stroke (S3 1.3% versus XT 3.1%, P=0.29) and all-cause mortality (S3 3.3% versus XT 4.5%, P=0.27). CONCLUSIONS: The use of the new generation S3 balloon-expandable THV reduced the risk of more than mild paravalvular regurgitation and vascular complications but was associated with an increased permanent pacemaker rate compared with the XT. Transcatheter aortic valve implantation using the newest generation balloon-expandable THV is associated with a low risk of stroke and favorable clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01368250.

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

BACKGROUND: The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. AIM: The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. DESIGN: Case control study. POPULATION: Eleven stroke survivors with spastic hemiplegia. METHODS: Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. RESULTS: None of the variable considered showed statistically significant changes after BoNT-A injection. CONCLUSION: The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. CLINICAL REHABILITATION IMPACT: The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.