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BACKGROUND: Aortic stenosis (AS) is the most common cause for valve replacement in the United States. The pathophysiology of AS involves obstruction to the left ventricular (LV) outflow and reduced arterial compliance. The intrinsic frequency (IF) method is a system-based approach for hemodynamic monitoring of the LV-arterial system and involves determination of ω1and ω2, which represent the dynamics of LV systolic and vascular function, respectively. Total frequency variation of the systemic circulation is the difference between these IFs (Δω = ω1- ω2). OBJECTIVE: Our goal in this study was to investigate whether Δω, obtained from the ascending aortic pressure waveform, can be indicative of LV-arterial coupling after transcatheter aortic valve replacement (TAVR). APPROACH: Thirty patients undergoing elective TAVR for severe, symptomatic AS were included. We applied the IF method to assess the immediate effects of TAVR on LV-arterial coupling. MAIN RESULTS: Mean age was 86 ±4 years, 50% were male with a mean aortic valve area of 0.7 cm2and mean ejection fraction (EF) of 59 ± 7%. The results showed a significant decrease in Δω (47.6 to 9.5 bpm, p < 0.00001) and a significant increase in ω2(51.9 to 84.6 bpm, p

International audience; A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen "a toxic environmental poison" could be also indispensable for life (Beckman and Ames Physiol Rev 78(2):547-81, 1998; Stadtman and Berlett Chem Res Toxicol 10(5):485-94, 1997)?: the so-called Oxygen Paradox (Davies and Ursini 1995; Davies Biochem Soc Symp 61:1-31, 1995). How can French people apparently disregard the rule that high dietary intakes of cholesterol and saturated fats (e.g., cheese and paté) will result in an early death from cardiovascular diseases (Renaud and de Lorgeril Lancet 339(8808):1523-6, 1992; Catalgol et al. Front Pharmacol 3:141, 2012; Eisenberg et al. Nat Med 22(12):1428-1438, 2016)?: the so-called, French Paradox. Doubtless, the truth is not a duality and epistemological bias probably generates apparently self-contradictory conclusions. Perhaps nowhere in biology are there so many apparently contradictory views, and even experimental results, affecting human physiology and pathology as in the fields of free radicals and oxidative stress, antioxidants, foods and drinks, and dietary recommendations; this is particularly true when issues such as disease-susceptibility or avoidance, "healthspan," "lifespan," and ageing are involved. Consider, for example, the apparently paradoxical observation that treatment with low doses of a substance that is toxic at high concentrations may actually induce transient adaptations that protect against a subsequent exposure to the same (or similar) toxin. This particular paradox is now mechanistically explained as "Adaptive Homeostasis" (Davies Mol Asp Med 49:1-7, 2016; Pomatto et al. 2017a; Lomeli et al. Clin Sci (Lond) 131(21):2573-2599, 2017; Pomatto and Davies 2017); the non-damaging process by which an apparent toxicant can activate biological signal transduction pathways to increase expression of protective genes, by mechanisms that are completely different from those by which the same agent induces toxicity at high concentrations. In this review, we explore the influences and effects of paradoxes such as the Oxygen Paradox and the French Paradox on the etiology, progression, and outcomes of many of the major human age-related diseases, as well as the basic biological phenomenon of ageing itself.

SUMMARY Aims: To describe the relation between emotional stress and cardiovascular events, and review the literature on the cardiovascular effects of emotional stress, in order to describe the relation, the underlying pathophysiology, and potential therapeutic implications. Materials and methods: Targeted PUBMED searches were conducted to supplement the authors’ existing database on this topic. Results: Cardiovascular events are a major cause of morbidity and mortality in the developed world. Cardiovascular events can be triggered by acute mental stress caused by events such as an earthquake, a televised high-drama soccer game, job strain or the death of a loved one. Acute mental stress increases sympathetic output, impairs endothelial function and creates a hypercoagulable state. These changes have the potential to rupture vulnerable plaque and precipitate intraluminal thrombosis, resulting in myocardial infarction or sudden death. Conclusion: Therapies targeting this pathway can potentially prevent acute mental stressors from initiating plaque rupture. Limited evidence suggests that appropriately timed administration of beta-blockers, statins and aspirin might reduce the incidence of triggered myocardial infarctions. Stress management and transcendental meditation warrant further study. Review criteria Dr. Kloner has extensive experience publishing on this topic and was familiar with the majority of the articles referenced in this manuscript. In addition, targeted PUBMED searches were conducted.

Background: Left main coronary artery (LMCA) bifurcation and heavily calcified lesions are common and challenging to treat percutaneously. Rotational atherectomy (RA) may be beneficial in this setting to facilitate stent placement though direct supporting evidence is lacking. This study sought to analyze patients who underwent RA of the LMCA. Methods: Consecutive cases involving RA of the LMCA between 1/1/2004 and 12/31/2009 at a private, tertiary referral hospital were reviewed retrospectively. Medical records, angiograms and clinically driven follow-up were reviewed. Results: Thirty-one cases were identified (20 protected, 11 unprotected), including 23 with stent implantation (21 drug-eluting, 2 bare metal). All 31 lesions had moderate to severe calcification, 84% involved the distal segment. Mean burr-to-vessel ratio was 0.43. Overall angiographic success was 90% (28/31) and was higher with a drug-eluting stent versus no stent (100% vs. 62%; P = 0.0153). In-hospital major adverse cardiovascular events (MACE) occurred in 1 patient (3%). Mid-term MACE occurred in 6 patients (26%) and tended to occur less frequently in patients with protected LMCAs (P = 0.0697). At final follow-up, patients were more likely to be alive and free from angina with a protected LMCA (94% vs. 57% unprotected; P = 0.0564) and with a drug-eluting stent (89% vs. 50% with no stent; P = 0.0281). Conclusions: RA of the LMCA to facilitate stent implantation appears to be safe and effective with favorable mid-term outcomes. In the setting of severe calcification and distal LMCA involvement RA and drug-eluting stent implantation should be considered. Cardiol Res. 2011;2(5):208-217 doi: https://doi.org/10.4021/cr78w

Coronary heart disease affects 7.6% of the population in the United States, where > 900,000 myocardial infarctions (MIs) occur annually. Approximately half of all MIs have an identifiable clinical trigger. Myocardial ischemia, MI, sudden cardiac death, and thrombotic stroke each occur with circadian variation and peak after waking in the morning. In addition, physical exertion and mental stress are common precipitants of MI. Waking in the morning, physical exertion, and mental stress influence a number of physiologic parameters, including blood pressure, heart rate, plasma epinephrine levels, coronary blood flow, platelet aggregability, and endothelial function. Upregulation of sympathetic output and catecholamines increase myocardial oxygen demand and can decrease myocardial oxygen supply and promote thrombosis. Ischemia ensues when myocardial oxygen demand exceeds supply. Increases in blood pressure and ventricular contractility increase intravascular shear stress and may cause vulnerable atherosclerotic plaques to rupture, forming a nidus for thrombosis that can precipitate MI. Numerous clinical triggers of MI have been identified, including blizzards, the Christmas and New Year's holidays, experiencing an earthquake, the threat of violence, job strain, Mondays for the working population, sexual activity, overeating, smoking cigarettes, smoking marijuana, using cocaine, and particulate air pollution. Avoiding clinical triggers or participating in therapies that prevent clinical triggers from precipitating cardiac events could potentially postpone clinical events by several years and improve cardiovascular morbidity and mortality. Direct or indirect evidence suggests that the risk of triggered MIs is reduced with β-blockers, aspirin, statins, stress management, and transcendental meditation.

To determine clinical outcomes of patients who underwent percutaneous revascularization (PR) with multiple devices.PR cases at a private, tertiary referral hospital were reviewed retrospectively. Limb salvage and patency rates were calculated by the Kaplan Meier method. Historical and procedural factors were analyzed by multivariate Cox proportional hazards models.We identified 66 patients and 87 limbs with 261 lesions, including 38 patients with critical limb ischemia (CLI) (51 limbs, 171 lesions). PR incorporated multiple devices (2.0 ± 1.2 devices/lesion, 2.4 ± 1.6 devices/procedure), including balloon angioplasty (57%), excisional atherectomy (54%), orbital atherectomy (44%), and stenting (13%). Last imaged patency was at 18 ± 13 months and last clinical follow-up was 22 ± 12 months. Thirty-five of 87 limbs had ≥1 repeat PR. In 51 limbs with CLI, limb salvage was 75% at 3 years. Independent predictors of amputation were higher creatinine (P=.01; hazard ratio [HR], 1.4), Rutherford category (P=.03; HR, 3.5), and history of coronary artery bypass graft (CABG) (P=.03; HR, 8.9). Overall patency remained 75% through 3 years. Loss of patency or primary patency (patency without repeat PR) was predicted by higher creatinine, Rutherford category, chronic total occlusion, history of CABG, female gender, current and past smoking. Use of excisional atherectomy maintained overall patency (P=.01; HR, 0.36).An aggressive approach to PR with frequent use of atherectomy resulted in high rates of limb salvage and patency. Smoking cessation and excisional atherectomy may improve patency rates.

This report focuses on cardioprotection and describes the advantages and disadvantages of various methods of inducing therapeutic hypothermia (TH) with regard to neuroprotection and cardioprotection for patients with cardiac arrest and ST-segment elevation myocardial infarction (STEMI). TH is recommended in cardiac arrest guidelines. For patients resuscitated after out-of-hospital cardiac arrest, improvements in survival and neurologic outcomes were observed with relatively slow induction of TH. More rapid induction of TH in patients with cardiac arrest might have a mild to modest incremental impact on neurologic outcomes. TH drastically reduces infarct size in animal models, but achievement of target temperature before reperfusion is essential. Rapid initiation of TH in patients with STEMI is challenging but attainable, and marked infarct size reductions are possible. To induce TH, a variety of devices have recently been developed that require additional study. Of particular interest is transcoronary induction of TH using a catheter or wire lumen, which enables hypothermic reperfusion in the absence of total-body hypothermia. At present, the main methods of inducing and maintaining TH are surface cooling, endovascular heat-exchange catheters, and intravenous infusion of cold fluids. Surface cooling or endovascular catheters may be sufficient for induction of TH in patients resuscitated after out-of-hospital cardiac arrest. For patients with STEMI, intravenous infusion of cold fluids achieves target temperature very rapidly but might worsen left ventricular function. More widespread use of TH would improve survival and quality of life for patients with out-of-hospital cardiac arrest; larger studies with more rapid induction of TH are needed in the STEMI population.

Background: Patients with cardiogenic shock (CS) are routinely treated with intra-aortic balloon pumps (IABPs). The utility of 2 new percutaneous left ventricular assist devices (PLVADs), the Impella and TandemHeart, is unknown. The objective of this study was to describe the use of PLVADs for patients with CS at our institution. Methods: All cases involving PLVADs in patients with CS between between January 1, 2008 and June 30, 2010 at a private, tertiary referral hospital were reviewed retrospectively. Results: All 76 cases were identified (50 IABP only, 7 Impella, 19 TandemHeart). Most Impella (5/7) and TandemHeart (10/19) patients were initially treated with an IABP before "upgrading" for increased hemodynamic support. All 76 devices (100%) were initiated successfully. Percutaneous revascularization was attempted in 63 patients with angiographic success in 57 (90%). The incidences of major complications were similar between groups, except bleeding occurred less frequently with the IABP. Mean ejection fraction on presentation was 30.4±16.5% and increased by a mean of 6.6±11.4% (P < 0.001). With the institutional approach of treating patients with CS initially with vasopressors and IABPs, then upgrading to an Impella or TandemHeart device for patients refractory to IABP therapy, the overall mortality rate was 40%. Conclusion: The Impella and TandemHeart devices can be initiated successfully in patients with CS, are associated with high rates of angiographic success during high risk percutaneous interventions and may benefit the myocardium during myocardial infarction. Randomized trials are warranted investigating use of the Impella and TandemHeart devices in patients with CS and in patients refractory to conventional IABP therapy. Cardiol Res. 2012;3(2):54-66 doi: https://doi.org/10.4021/cr121w

Intra-aortic balloon pumps (IABPs) are indicated during high-risk percutaneous coronary intervention (HR-PCI) to reduce major procedural complications. The clinical utility of the newer Impella and TandemHeart devices is not clear. This study determined the baseline characteristics, hemodynamics, and outcomes of patients treated with prophylactic percutaneous left ventricular assist devices (PLVADs) during HR-PCI.A retrospective analysis at a private, tertiary referral hospital was conducted of all cases involving prophylactic PLVAD during HR-PCI between January 1, 2008 and June 30, 2010. General practice in this institution involves a tiered approach to PLVAD whereby patients with the least, intermediate, and highest risk of left ventricular failure are treated with an IABP, Impella, or TandemHeart, respectively.Fifty cases were identified (5 IABP, 13 Impella, 32 TandemHeart). Mean ejection fraction was 31 ± 17%. All devices (100%) were initiated successfully. Angiographic success was achieved in 96% (80% IABP, 100% Impella, 97% TandemHeart). Of the 38 patients not in cardiogenic shock, death occurred in 1 (2.6%), recurrent ischemia in 3 (8%), and stroke in 0%. Shortly after device removal, systolic blood pressure (mean increase, +5 ± 22 mmHg) and ejection fraction (mean increase, +7.4 ± 11%; p = 0.0006) increased in all 3 groups, suggesting a beneficial effect on the myocardium.In patients undergoing HR-PCI with Impella and TandemHeart support, angiographic success was high and major complication rates were low. A tiered approach where patients with the least, intermediate, and highest risk of left ventricular failure are treated with an IABP, Impella, or Tandem- Heart, respectively, theoretically maximizes appropriate hemodynamic support and minimizes complications. Further studies are warranted.

In heavily calcified lesions, rotational atherectomy (RA) improves procedural success and facilitates stent deployment. Reports on RA in the drug-eluting stent (DES) era are limited. The objective of this study was to determine the presenting characteristics, procedural and in-hospital clinical outcomes of patients who underwent RA at our institution in the DES era.Consecutive cases involving RA between January 1, 2004 and December 31, 2009 at a private, tertiary referral hospital were reviewed retrospectively.A total of 158 patients (236 lesions) who underwent RA are described, including 112 patients (158 lesions) with subsequent DES implantation, 19 patients (28 lesions) with bare-metal stent (BMS) implantation, and 27 patients (50 lesions) with no stent. RA was utilized to modify heavily calcified plaque (84%), as bail-out therapy (16%), to preserve the patency of sidebranches (25%) and as debulking therapy for chronic total occlusion (13 lesions) and in-stent restenosis (7 lesions). DES were not placed in 46 patients (23%) due to reference vessel diameter2.25 or3.75 mm, inability to deliver DES, or desire to avert clopidogrel therapy. Angiographic and procedural success rates were significantly higher in the DES and BMS groups compared with the no stent group (angiographic success: 99.1% for DES versus 95% for BMS versus 63% for no stent; p0.05; procedural success: 96.4% for DES versus 95% for BMS versus 63% for no stent; p0.05).In the DES era, RA remains utilized primarily to modify heavily calcified plaque. In unadjusted analysis, procedural success appears high with subsequent stent placement (DES or BMS) versus RA alone. However, 1 in 4 are not candidates for stent placement, and the lower procedural success rate in this population should be considered prior to embarking on RA.

Vascular access-site complications are an important cause of morbidity following catheterization procedures. Manual compression is the "gold standard" in achieving hemostasis of an arteriotomy site; however, manual compression is limited by the need to interrupt anticoagulation, prolonged bed rest, patient discomfort and time demands for healthcare providers. Vascular closure devices (VCDs) improve patient comfort, free medical staff resources and shorten the time needed for hemostasis, ambulation and discharge. However, the safety of VCDs remains in question and they may increase the risks of infection and leg ischemia. Compared with manual compression, the rate of major complications appears to be increased with VasoSeal, decreased with Angio-Seal and decreased in diagnostic cases with Perclose. The safety of VCDs cannot be assumed due to "class effect," and nearly all individual trials are underpowered to detect differences in complication rates, so the safety of other individual VCDs is unclear. In the absence of puncture site-related risk factors, VCDs as a whole appear to have little influence on complication rates, and patients at high baseline risk for bleeding due to clinical factors may benefit from these devices. Screening with femoral angiography prior to VCD placement and avoidance of VCDs in the presence of puncture site-related risk factors might reduce the risk of vascular complications. This review describes the mechanism, efficacy and safety of VCDs including hemostasis pads, the FemoStop, Clamp Ease, Mynx, Duett, FISH, Boomerang, ExoSeal, Starclose, VasoSeal, Angio-Seal and Perclose devices.

We sought to describe the use of the TandemHeart percutaneous left ventricular assist device (PVAD) in a group of high-risk patients undergoing complex cardiovascular procedures.There is a substantial risk of acute decompensation and death in patients with cardiogenic shock or a reduced cardiac reserve undergoing high-risk cardiovascular interventions. The TandemHeart PVAD provides near-total hemodynamic support in this setting.Thirty-seven high-risk patients underwent placement of the TandemHeart PVAD during 38 separate procedures between April 2007 and April 2009. PVAD insertion was considered emergent if a patient was not expected to survive more than 6 hours without PVAD support. Technical success was defined as successful initiation of the PVAD and completion of the intended interventional procedure.All 37 patients were in cardiogenic shock or undergoing complex coronary and valvular interventions with a high probability of hemodynamic collapse. The mean (+/- standard deviation) patient age was 73 +/- 14 years; 97% were in either NYHA class III-IV heart failure or cardiogenic shock; and the mean EuroSCORE was 11 +/- 3.4. Indications for ventricular assist device placement included critical aortic stenosis (n = 8), severe left main coronary stenosis (n = 18), severe multivessel coronary stenosis (n = 19) and severe cardiomyopathy (n = 23). Four patients were being managed for fulminant myocarditis, ventricular free-wall rupture, flail mitral valve or severe paravalvular leak. Despite their critical status and frequent (82%) need for post-procedure blood transfusion, this complex and high-risk patient population tolerated PVAD-supported intervention well and technical success was achieved in all patients. Seventy-one percent of patients survived to hospital discharge with improved functional status. Most deaths occurred in patients not expected to survive due to their moribund status and multiorgan failure.This experience demonstrates the utility and effectiveness of TandemHeart PVAD support in patients with advanced disease, critical clinical status and limited therapeutic options.

Endothelial cells have numerous endocrine functions and contribute to a variety of processes, including penile erection and vasodilation. Endothelial dysfunction is associated with cardiovascular risk factors and has been implicated in the pathogenesis of atherosclerosis and ED. This study reviews endothelial function, in addition to endothelial dysfunction and its role in atherosclerosis and ED. Measurement of endothelial function is reviewed, including catheter-based methods, venous occlusion plethysmography, high-frequency ultrasound, peripheral arterial tonometry, digital pulse amplitude tonometry, digital thermal monitoring, the L-arginine test and measurement of compounds released by endothelial cells. Therapy and medications that improve endothelial function are reviewed. As the scientific community learns more about the importance of the endothelium, it is increasingly important for the clinician to understand endothelial function, dysfunction, measurement of endothelial function and therapies that affect this remarkable cell type.

Levosimendan increases the sensitivity of the cardiac fibrils to calcium, favorably affects hemodynamics in patients with heart failure. It is a positive inotrope and a peripheral vasodilator. The elimination half-life of the compound is about 1 hour. The drug decreases pulmonary capillary wedge pressure, increases cardiac output with the improvement in left ventricular ejection fraction leading to symptomatic improvement which includes decreased dyspnea and fatigue. Levosimendan can be used safely with diuretics, nitrates, beta-blockers, digoxin, and angiotensin-converting enzyme inhibitors. The most common adverse effects of levosimendan are headache and hypotension. Prolongation of the QTc interval does not appear to increase the incidence of arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Levosimendan is a novel agent in the treatment of decompensated heart failure, representing a newer class of medications aimed at increasing calcium sensitivity. Its properties holds promise for the treatment of heart failure but further large-scale studies will be needed to determine its precise efficacy, safety, as well as the compound's long-term impact on mortality.