Atrial flutter with multilevel atrioventricular block and cyclical occurrence of varying QRS morphologies.

An electrocardiogram showing atrial flutter in which varying ratios of AV conduction and the cyclical recurrence of varying QRS morphologies are observed is presented.

Advances in the management of atrial fibrillation with a special focus on non-pharmacological approaches to prevent thromboembolism: a review of current recommendations.

Atrial fibrillation (AFIB) is the most common heart rhythm abnormality and is associated with significant morbidity and mortality. While the treatment of AFIB involves strategies of rate with or without rhythm control, it is also essential to strategize appropriate therapies to prevent thromboembolic complications arising from AFIB. Previously, anticoagulation was the main treatment option which exposed patients to higher than usual risk of bleeding. However, with the advent of new technology, novel therapeutic options aimed at surgical or percutaneous exclusion or occlusion of the left atrial appendage in preventing thromboembolic complications from AFIB have evolved. This review evaluates recent advances and therapeutic options in treating AFIB with a special focus on both surgical and percutaneous interventions which can reduce and/or eliminate thromboembolic complications of AFIB.

Mechanical stress analysis of a rigid inclusion in distensible material: a model of atherosclerotic calcification and plaque vulnerability.

The role of atherosclerotic calcification in plaque rupture remains controversial. In previous analyses using finite element model analysis, circumferential stress was reduced by the inclusion of a calcium deposit in a representative human anatomical configuration. However, a recent report, also using finite element analysis, suggests that microscopic calcium deposits increase plaque stress. We used mathematical models to predict the effects of rigid and liquid inclusions (modeling a calcium deposit and a lipid necrotic core, respectively) in a distensible material (artery wall) on mechanical failure under uniaxial and biaxial loading in a range of configurations. Without inclusions, stress levels were low and uniform. In the analytical model, peak stresses were elevated at the edges of a rigid inclusion. In the finite element model, peak stresses were elevated at the edges of both inclusions, with minimal sensitivity to the wall distensibility and the size and shape of the inclusion. Presence of both a rigid and a soft inclusion enlarged the region of increased wall stress compared with either alone. In some configurations, the rigid inclusion reduced peak stress at the edge of the soft inclusion but simultaneously increased peak stress at the edge of the rigid inclusion and increased the size of the region affected. These findings suggest that the presence of a calcium deposit creates local increases in failure stress, and, depending on relative position to any neighboring lipid pools, it may increase peak stress and the plaque area at risk of mechanical failure.

Modulation of the sinus rate during ventricular fibrillation.

BACKGROUND: During supraventricular and ventricular tachycardia, the arterial baroreflex predominates with minimal contribution from the cardiopulmonary reflex. To our knowledge, the role of the arterial baroreflex gain (BRG) during and immediately following termination of ventricular fibrillation (VF) has not been characterized. OBJECTIVE: We hypothesized that (1) arterial BRG correlated with sinus node cycle length (SNCL) changes during VF, and that (2) the greater the arterial BRG, the greater the blood pressure (BP) recovery following successful defibrillation. METHODS: Arterial BRG was assessed in 18 patients referred for the implantation of a defibrillator incorporating an atrial lead. The average SNCL was measured during the 5 seconds prior to VF induction and the last 5 seconds during VF before defibrillation. Percent SNCL change (%DeltaSNCL) was determined. Arterial BP recovery was calculated as the difference in mean BP following defibrillation compared to during VF. RESULTS: Arterial BRG ranged between -3 and 18 ms/mmHg. During VF, SNCL shortened in 11 patients (group A, mean %DeltaSNCL =-15%), and surprisingly lengthened in seven patients (group B, mean %DeltaSNCL = 5%). There was no correlation between %DeltaSNCL and arterial BRG. In fact, arterial BRG in group A was lower when compared with group B (P = 0.075). Similarly, there was no correlation between arterial BRG and BP recovery. CONCLUSIONS: We found no correlation between arterial BRG and %DeltaSNCL during VF, or BP recovery following defibrillation. Our findings of SNCL lengthening in 7 of 18 patients suggest that in some patients, arterial BRG plays a minor role during VF with a greater contribution from the cardiopulmonary BRG.

Inappropriate ICD shocks for inappropriate reasons.

ICD shocks can result from a variety of etiologies; determining the proper etiology of the inappropriate shock is essential for correction of the problem. Electromagnetic interference (EMI) can mimic cardiac signals and cause inappropriate defibrillator shocks. We present two cases of inappropriate ICD shocks due to EMI and reversal of the proximal and distal DF-1 lead terminals of the ICD lead. These are two unusual etiologies for inappropriate defibrillator shocks.

Relation of osteoprotegerin to coronary calcium and aortic plaque (from the Dallas Heart Study).

Circulating osteoprotegerin (OPG) has been shown to be elevated in patients with vascular disease. The role of OPG as a biomarker for atherosclerosis in a large, unselected population is not well known. Plasma OPG levels were measured in 3,386 subjects in the Dallas Heart Study, a multiethnic, population-based probability sample of adults aged 30 to 65 years. Coronary artery calcium (CAC) was measured by electron beam computed tomography. Aortic plaque was assessed by magnetic resonance imaging. Multivariable logistic regression was used to assess associations among OPG, cardiovascular risk factors, CAC, and aortic plaque. Age, female gender, black race, smoking, personal and family history of coronary artery disease (CAD), diabetes mellitus, hyperlipidemia, CAC, and aortic plaque were significantly associated with higher plasma OPG levels (p <0.01) in univariable analyses. The prevalence of CAC and aortic plaque increased across OPG quartiles (p <0.001 for each). An OPG level in the fourth quartile was independently associated with CAC (RR 1.39, 95% confidence interval 1.01 to 1.93) and aortic plaque (RR 1.42, 95% confidence interval 1.09 to 1.86) after adjustment for age, gender, smoking, diabetes, hyperlipidemia, and family history of premature CAD. In conclusion, plasma OPG is independently associated with CAC and aortic plaque in an unselected population, suggesting it may be a novel biomarker for atherosclerosis in humans.

Heart rate turbulence parameters correlate with post-premature ventricular contraction changes in muscle sympathetic activity.

BACKGROUND: Heart rate turbulence (HRT) has been shown to be vagally mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) after a premature ventricular contraction (PVC) remains unclear. OBJECTIVE: We sought to evaluate the relationship between HRT and the changes in peripheral SNA after PVCs. METHODS: We recorded postganglionic muscle SNA during electrocardiogram monitoring in eight patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during (1) the dominant burst after the PVC (dominant burst area) and (2) the 10 seconds after the dominant burst (postburst SNA). RESULTS: The mean TO was 0.1% +/- 4.6%, and the mean TS was 6.1 +/- 6.6. The dominant burst area negatively correlated with TO (r = -0.50, P = .0002). The postburst SNA showed a significant positive correlation with TO (r = 0.44, P = .001) and a negative correlation with TS (r = -0.42, P = .002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. CONCLUSIONS: Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease.

The effects of rate and irregularity on sympathetic nerve activity in human subjects.

BACKGROUND: We have recently shown that atrial fibrillation is associated with an increase in sympathetic nerve activity (SNA) compared with sinus rhythm. It remains unclear, however, whether these findings are true at various rates and whether the magnitude of sympathoexcitation is related to the degree of irregularity. OBJECTIVE: To determine the role of irregularity in mediating the SNA changes at various pacing rates. Univariate analysis showed that as the irregularity increased, SBP increased (r = 0.44, P < .001) but that MAP and DBP did not change significantly. METHODS: Using custom-made software, atrioventricular sequential pacing with predetermined rates (100, 120, and 140 bpm) and irregularities (standard deviation = 0%, 5%, 15%, and 25% of mean cycle length) was performed in 23 patients referred for electrophysiologic evaluation. Pacing at each rate/irregularity was performed for 2 minutes, with 2 minutes of recovery in between. Systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MAP), central venous pressure (CVP), and SNA were measured at baseline and during pacing. RESULTS: Univariate analysis showed that as the irregularity increased, SBP increased (r = 0.44, P < .001 but that MAP and DBP did not change significantly. A significant correlation was found between the pacing irregularity and SNA, with greater sympathoexcitation noted at greater degrees of irregularity (r = 0.2, P = .04). A five-variable linear model using DBP, MAP, CVP, and degree of pacing irregularity to predict SNA was highly statistically significant (r = 0.46, P < .001). After controlling for hemodynamic changes, for every 1% increase in irregularity, there was a 6.1% increase in SNA. CONCLUSION: We have shown that greater degrees of irregularity cause greater sympathoexcitation and that the effects of irregular pacing on SNA are independent of the hemodynamic changes.

Insulin-like growth factor-I regulates proliferation and osteoblastic differentiation of calcifying vascular cells via extracellular signal-regulated protein kinase and phosphatidylinositol 3-kinase pathways.

Vascular calcification develops within atherosclerotic lesions and results from a process similar to osteogenesis. One of the paracrine regulators of bone-derived osteoblasts, insulin-like growth factor-I (IGF-I), is also present in atherosclerotic lesions. To evaluate its possible role in vascular calcification, we assessed its in vitro effects on proliferation and differentiation in calcifying vascular cells (CVCs), a subpopulation of bovine aortic medial cells. Results showed that IGF-I inhibited spontaneous CVC differentiation and mineralization as evidenced by decreased alkaline phosphatase (AP) activity and decreased matrix calcium incorporation, respectively. Furthermore, IGF-I inhibited the AP activity induced by bacterial lipopolysaccharide, TNF-alpha, or H2O2. It also induced CVC proliferation based on 3H-thymidine incorporation. Results from Northern analysis and tests using IGF-I analogs suggest that IGF-I effects are mediated through the IGF-I receptor. IGF-I also activated both the extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) pathways. Inhibition of either the ERK or PI3K pathway reversed IGF-I effects on CVC proliferation and AP activity, suggesting a common downstream target. Overexpression of ERK activator also mimicked IGF-I inhibition of lipopolysaccharide-induced AP activity. These results suggest that IGF-I promotes proliferation and inhibits osteoblastic differentiation and mineralization of vascular cells via both ERK and PI3K pathways.

Failure to Treat Life-Threatening Ventricular Tachyarrhythmias in Contemporary Implantable Cardioverter-Defibrillators: Implications for Strategic Programming.

BACKGROUND: In clinical trials, manufacturer-specific, strategic programming of implantable cardioverter-defibrillators (ICDs), including faster detection rates, reduces unnecessary therapy but permits therapy for ventricular tachycardia/ventricular fibrillation (VF). Present consensus recommends a generic rate threshold between 185 and 200 beats per minute, which exceeds the rate tested in clinical trials for some manufacturers. In a case series, we sought to determine the relationship between programmed parameters and failure of modern ICDs to treat VF. METHODS AND RESULTS: We reviewed cases in which normally functioning ICDs failed to deliver timely therapy for VF from April 2015 to January 2017 at 4 institutions. Of 10 ambulatory patients, 5 died from untreated VF, 4 had cardiac arrests requiring external shocks, and 1 was rescued by a delayed ICD shock. VF did not satisfy programmed detection criteria in 9 patients (90%). Seven of these patients had slowest detection rates that were consistent with generic recommendations but not tested in a peer-reviewed trial for their manufacturer's ICDs. Manufacturer-specific factors interacted with fast detection rates to withhold therapy, including strict VF episode termination rules, enhancements to minimize T-wave oversensing, and features that restrict therapy to regular rhythms in ventricular tachycardia zones. Untreated VF despite recommended programming accounted for 56% of sudden deaths and 11% of all deaths during the study period. CONCLUSIONS: Complex and unanticipated interactions between manufacturer-specific features and generic programming can prevent therapy for VF. More data are needed to assess the risks and benefits of translating evidence-based detection parameters from one manufacturer to another.

Mesenchymal stem cells and the artery wall.

The presence of ectopic tissue in the diseased artery wall is evidence for the presence of multipotential stem cells in the vasculature. Mesenchymal stem cells were first identified in the marrow stroma, and they differentiate along multiple lineages giving rise to cartilage, bone, fat, muscle, and vascular tissue in vitro and in vivo. Transplantation studies show that marrow-derived mesenchymal stem cells appear to enter the circulation and engraft other tissues, including the artery wall, at sites of injury. Recent evidence indicates that mesenchymal stem cells are also present in normal artery wall and microvessels and that they also may enter the circulation, contributing to the population of circulating progenitor cells and engrafting other tissues. Thus, the artery wall is not only a destination but also a source of progenitor cells that have regenerative potential. Although potential artifacts, such as fusion, need to be taken into consideration, these new developments in vascular biology open important therapeutic avenues. A greater understanding of how mesenchymal stem cells from the bone marrow or artery wall bring about vascular regeneration and repair may lead to novel cell-based treatments for cardiovascular disease.

Acute coronary syndrome after infliximab infusion.

The TNFalpha inhibitor infliximab is widely used in the treatment of rheumatoid arthritis and Crohn disease. Mild infusion reactions consisting of low-grade fever, headache, nausea, and fatigue are common, but we describe for the first time the occurrence of an acute coronary syndrome during infliximab administration. This case alerts infusion centers to consider the possibility that chest pain and dyspnea during infliximab infusion can represent a myocardial infarction, even in younger patients without a history of cardiac disease.

Vascular calcification: mechanisms and clinical ramifications.

Vascular calcification, long thought to result from passive degeneration, involves a complex, regulated process of biomineralization resembling osteogenesis. Evidence indicates that proteins controlling bone mineralization are also involved in the regulation of vascular calcification. Artery wall cells grown in culture are induced to become osteogenic by inflammatory and atherogenic stimuli. Furthermore, osteoclast-like cells are found in calcified atherosclerotic plaques, and active resorption of ectopic vascular calcification has been demonstrated. In general, soft tissue calcification arises in areas of chronic inflammation, possibly functioning as a barrier limiting the spread of the inflammatory stimulus. Atherosclerotic calcification may be one example of this process, in which oxidized lipids are the inflammatory stimulus. Calcification is widely used as a clinical indicator of atherosclerosis. It progresses nonlinearly with time, following a sigmoid-shaped curve. The relationship between calcification and clinical events likely relates to mechanical instability introduced by calcified plaque at its interface with softer, noncalcified plaque. In general, as calcification proceeds, interface surface area increases initially, but eventually decreases as plaques coalesce. This phenomenon may account for reports of less calcification in unstable plaque. Vascular calcification is exacerbated in certain clinical entities, including diabetes, menopause, and osteoporosis. Mechanisms linking them must be considered in clinical decisions. For example, treatments for osteoporosis may have unanticipated effects on vascular calcification; the converse also applies. Further understanding of processes governing vascular calcification may yield new therapeutic options for vascular disease.

Case report: Radiofrequency catheter ablation of typical atrial flutter and the atrioventricular junction via the superior vena caval approach in a patient with a congenital absence of an inferior vena cava.

The absence of an inferior vena cava is a rare congenital condition often without clinical significance. Alternative venous approaches are often needed to treat these patients. We report a case of successful ablation of both isthmus dependent flutter and the AV junction using the superior vena cava in a patient with an inferior vena cava anomaly.

Linear left atrial lesions in minimally invasive surgical ablation of persistent atrial fibrillation: techniques for assessing conduction block across surgical lesions.

Minimally invasive surgical (MIS) ablation, with pulmonary vein (PV) isolation and ganglionated plexi (GP) ablation, has proven highly successful for paroxysmal atrial fibrillation but has limited success in patients with persistent and long-standing persistent (P-LSP) AF. A set of linear left atrial (LA) lesions has been added to interrupt some macroreentrant components of P-LSP AF. This includes a Transverse Roof Line and Left Fibrous Trigone Line (from Roof Line to mitral annulus at the left fibrous trigone). With complete conduction block (CCB), these lesions should prevent single- or double-loop macroreentrant LA tachycardias from propagating around the PVs or mitral annulus. It is critical to identify whether CCB has been achieved and, if not, to locate the gap for further ablation, since residual gaps will support macroreentrant atrial tachycardias. Confirming CCB involves pacing close to one side of the ablation line and determining the direction of activation on the opposite side, by recording close bipolar electrograms at multiple paired sites (perpendicular and close to the ablation line) along the entire length of the line. Simpler approaches have been used, but all have limitations, especially when the conduction time across a gap is long. The extended lesion set was created after PV isolation and GP ablation in 14 patients with P-LSP AF. Mapping after the first set of radiofrequency applications for the Transverse Roof and Left Trigone Lines confirmed CCB in only 3/14 (21%) patients for each line, showing the importance of checking for CCB. During follow-up (median 8 months), 10/14 (71%) patients had no symptoms of atrial arrhythmia (7/10 off antiarrhythmic drugs). Of the remaining four patients, three have only infrequent episodes (self-terminating in 2/3). These preliminary results suggest that adding Roof and Trigone Lines may increase MIS success in patients with P-LSP AF. Accurate mapping techniques verify CCB and effectively locate gaps in ablation lines for further ablation.