Intravascular lithotripsy in calcified-coronary lesions: A real-world observational, European multicenter study.

BACKGROUND: The recently introduced intravascular lithotripsy (IVL) appears promising and relatively safer than conventional approaches when dealing with calcified lesions. Although there are published reports on this novel technology, data from the real world are limited. In this study, we aim to report on the experience of IVL from a real-world population derived from six European centers that undertake high-volume complex coronary interventions. METHODS AND RESULTS: We enrolled all patients treated with IVL between November 2018 and February 2020 at six centers. Procedural success and complications were assessed along with clinical outcomes, which included: cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR), and major adverse cardiac event (MACE) (composite of cardiac death, TVMI, and TLR). Hundred and ninety patients (200 lesions) with a mean age of 72 years were treated using IVL. Diabetes and chronic kidney disease were present in 50% (n = 95) and 16% (n = 30) of cases, respectively. Acute-coronary syndromes accounted for 91 (48%) of the cases. Most were de-novo lesions (77%; n = 154). Upfront use of IVL occurred in 26% of cases, while the rest were bail-out procedures due to inadequate predilatation with conventional balloons. Adjuvant rotational atherectomy was needed in 17% of cases. Procedural success was achieved in 99% of cases with a complication rate of 3%. During the median follow-up of 222 days, there was two cardiac deaths (1%), one case of TVMI (0.5%), 3 TLR (1.5%) taking the MACE rate to 2.6%. CONCLUSION: Use of IVL appears to be safe and effective in dealing with calcified-coronary lesions. A high success rate was observed with low procedural complications and event rates.

Successful treatment of aortic root rupture following transcatheter aortic valve implantation in a heavily calcified aorta: a novel approach to a serious complication.

Aortic root rupture during transcatheter aortic valve implantation (TAVI) is an uncommon but almost uniformly fatal complication. We describe a novel surgical management of this complication using a combination of pledgeted sutures and prolonged direct digital compression with biomatrix and lattice adjuncts. Furthermore, our patient underwent percutaneous coronary intervention with endothelial progenitor cell-capturing stents, which facilitated TAVI to be performed off clopidogrel therapy. We believe the use of these stents reduced the severity of hemorrhage following aortic root rupture and helped maintain vessel patency following prolonged hypotension.

Nuclear and chloroplast DNA phylogeography reveals Pleistocene divergence and subsequent secondary contact of two genetic lineages of the tropical rainforest tree species Shorea leprosula (Dipterocarpaceae) in South-East Asia.

Tropical rainforests in South-East Asia have been affected by climatic fluctuations during past glacial eras. To examine how the accompanying changes in land areas and temperature have affected the genetic properties of rainforest trees in the region, we investigated the phylogeographic patterns of a widespread dipterocarp species, Shorea leprosula. Two types of DNA markers were used: expressed sequence tag-based simple sequence repeats and chloroplast DNA (cpDNA) sequence variations. Both sets of markers revealed clear genetic differentiation between populations in Borneo and those in the Malay Peninsula and Sumatra (Malay/Sumatra). However, in the south-western part of Borneo, genetic admixture of the lineages was observed in the two marker types. Coalescent simulation based on cpDNA sequence variation suggested that the two lineages arose 0.28-0.09 million years before present and that following their divergence migration from Malay/Sumatra to Borneo strongly exceeded migration in the opposite direction. We conclude that the genetic structure of S. leprosula was largely formed during the middle Pleistocene and was subsequently modified by eastward migration across the subaerially exposed Sunda Shelf.

Long-term antiplatelet therapy: from clinical trials to clinical application.

PURPOSE OF REVIEW: This review seeks to describe the emerging clinical trial data that informs clinical practice with regards to dual antiplatelet therapy. RECENT FINDINGS: Recent evidence with vorapaxar has demonstrated an increase in bleeding events with only modest improvement in ischemic outcomes. Platelet function testing to inform clopidogrel dose selection has not shown improvement in clinical outcome. The impact of CYP2C19 loss-of-function alleles on clopidogrel effect may be more modest than initially reported, though an impact on stent thrombosis is evident. Among patients receiving current generation drug eluting stents, 6 months of dual antiplatelet therapy may provide similar ischemic outcomes with fewer bleeding events compared with 12 or 24 months of therapy. Novel anticoagulants entering clinical practice will also potentially influence the clinical decisions regarding the duration of dual antiplatelet therapy. Studies focussing on the discontinuation of aspirin as opposed to the P2Y12 inhibitor to reduce late bleeding risk should be considered. SUMMARY: Evolving evidence and new therapies may enable shorter duration dual antiplatelet therapy.

Promise of factor Xa inhibition in acute coronary syndromes.

Drugs that inhibit factor Xa have been shown to reduce mortality and morbidity in acute coronary syndromes (ACS). Presently, factor Xa inhibition is most often achieved indirectly with the heparins and, increasingly, fondaparinux. Despite effective anticoagulation with indirect factor Xa inhibition there remains considerable mortality and morbidity in ACS. The recently developed direct factor Xa inhibitors (the xabans) appear to offer promise as alternatives to the heparins. We review the evidence behind indirect and direct factor Xa inhibition in non-ST-segment elevation ACS, ST-segment elevation myocardial infarction, and with percutaneous coronary intervention.

"RotaTripsy" for Severe Calcified Coronary Artery Lesions: Insights From a Real-World Multicenter Cohort.

OBJECTIVES: The aim of this study is to assess the feasibility, efficacy and safety of the "RotaTripsy" approach in severe calcified coronary artery lesions. BACKGROUND: Coronary lesions with a high calcium content represent a challenging scenario in interventional cardiology, requiring a proper lesion preparation. In this light, very little is known about the possibility to combine the benefits of rotational atherectomy and intravascular lithotripsy. METHODS: We retrospectively enrolled 34 patients from a real-word, multicenter, cohort of patients affected by severe calcified coronary artery lesions, which required the "RotaTripsy" to obtain a proper lesion preparation. In all the cases, rotational atherectomy and then intravascular lithotripsy were performed as a bail-out strategy following sub-optimal non-compliant balloon expansion. In 53% of the cases, the procedure was guided by intracoronary imaging findings. RESULTS: Procedural success was reported in all the cases, without any in-hospital major complication. Few major adverse clinical events were reported at mid-term follow-up. CONCLUSIONS: "RotaTripsy" can represent a valid therapeutic option for undilatable heavily calcified coronary artery lesions. Our findings demonstrate the feasibility, safety and efficacy of this approach.

Complete Genome Sequences of Microbacterium Bacteriophages Danno, Otwor, and Scumberland, Isolated in Clarksville, Tennessee.

This paper reports the genome sequences of bacteriophages isolated from soil samples using Microbacterium foliorum Phages Danno and Otwor (cluster EE) have genomes of 17,452 bp and 17,454 bp, respectively, and 25 predicted genes. The phage Scumberland (cluster EC) has a genome of 53,276 bp with 92 predicted genes.

Improved Nylon 6,6 Nanofiber Membrane in A Tilted Panel Filtration System for Fouling Control in Microalgae Harvesting.

The competitiveness of algae as biofuel feedstock leads to the growth of membrane filtration as one of promising technologies for algae harvesting. Nanofiber membrane (NFM) was found to be efficient for microalgae harvesting via membrane filtration, but it is highly limited by its weak mechanical strength. The main objective of this study is to enhance the applicability of nylon 6,6 NFM for microalgae filtration by optimizing the operational parameters and applying solvent vapor treatment to improve its mechanical strength. The relaxation period and filtration cycle could be optimized to improve the hydraulic performance. For a cycle of 5 min., relaxation period of ≤2 min shows the highest steady-state permeability of 365 ± 14.14 L m-2 h-1 bar-1, while for 10 min cycle, 3 min. of relaxation period was found optimum that yields permeability of 402 ± 34.47 L m-2 h-1 bar-1. The treated nylon 6,6 NFM was also used to study the effect of aeration rate. It is confirmed that the aeration rate enhances the steady-state performance for both intermittent and continuous mode of aeration. Remarkably, intermittent aeration shows 7% better permeability than the full aeration for all tested condition, which is beneficial for reducing the total energy consumption.

Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment.

BACKGROUND: Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients. METHODS AND RESULTS: In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (VO2max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in VO2max (16.1+/-0.6 to 18.8+/-1.1 mL . kg(-1) . min(-1); P<0.001), quality of life (Minnesota score reduction from 45+/-5 to 34+/-5; P=0.04), and left ventricular ejection fraction (24+/-1% to 34+/-2%; P<0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period. CONCLUSIONS: In patients with CHF, metabolic modulation with perhexiline improved VO2max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.

Modification of myocardial substrate use as a therapy for heart failure.

Despite advances in treatment, chronic heart failure is still associated with significant morbidity and a poor prognosis. The scope for further advances based on additional neurohumoral blockade is small. Effective adjunctive therapies acting via a different cellular mechanism would, therefore, be attractive. Energetic impairment seems to contribute to the pathogenesis of heart failure. The findings from several studies have shown that the so-called metabolic agents could have potential as adjunctive therapies in heart failure. These agents cause a shift in the substrate used by the heart away from free fatty acids, the oxidation of which normally provides around 70% of the energy needed, towards glucose. The oxygen cost of energy generation is lessened when glucose is used as the substrate. In this review we aim to draw attention to the metabolic alteration in heart failure and we present evidence supporting the use of metabolic therapy in heart failure.

Effects of aldosterone on forearm vasculature in treated chronic heart failure.

The nongenomic effects of aldosterone in disease states associated with endothelial dysfunction may differ from those in healthy subjects. The effects of locally infused aldosterone on the forearm blood flow and volume were studied in optimally treated patients with chronic heart failure (CHF). At baseline and after incremental intrabrachial aldosterone, forearm blood flow was assessed using conventional strain gauge plethysmography, and forearm venous volume was assessed by radionuclide plethysmography. Constriction of the resistance vasculature of the forearm without significant effect on forearm venous capacitance was demonstrated in response to aldosterone in patients treated for CHF.

Atrial natriuretic peptide regulates regional vascular volume and venous tone in humans.

OBJECTIVE: To date, the contribution of basal atrial natriuretic peptide (ANP) levels to resting vascular function in humans is unknown. In the present study we sought to investigate the role of ANP in regulating regional vascular volume and venous tone in healthy subjects. METHODS AND RESULTS: We used radionuclide plethysmography to examine the effects of ANP and the ANP-receptor antagonist A71915 on forearm vascular volume. Creating pressure/volume relations, we determined changes in vascular volume, compliance, and tone. Performing dose-ranging studies, we additionally assessed the potency and specificity of A71915 in the forearm resistance vasculature. Equilibrium blood pool scintigraphy was then used to assess the effects of systemic administration of A71915 on regional intestinal vascular volume. Infusion of ANP increased forearm vascular volume in a dose-dependent manner (maximum 20%; P<0.001), exerting a maximum venodilating effect at plasma levels similar to that seen in heart failure. A71915 increased venous tone, thereby decreasing vascular volume by 9.6+/-1.1%, P<0.001 (forearm), and 2.6+/-0.5%, P=0.01 (intestinal beds). At an infusion ratio of 50:1, A71915 almost completely abolished the effects of ANP on forearm blood flow. CONCLUSIONS: ANP locally regulates regional vascular volume and tone without affecting compliance.

Effects of exogenous and endogenous natriuretic peptides on forearm vascular function in chronic heart failure.

OBJECTIVE: Natriuretic peptides (NPs) reduce central venous pressure in patients with chronic heart failure (cHF) despite attenuation of arterial, renal, and humoral effects. This suggests a preserved venodilator response. This study had 4 aims: to compare the venodilator effects of human NPs in patients with cHF; to assess the contribution of basal ANP and BNP levels to regulation of forearm vascular volume (FVV); to test the hypothesis that venous ANP responsiveness is preserved in cHF; and to assess the involvement of endothelial nitric oxide-synthase (eNOS) in NP-induced vascular effects. METHODS AND RESULTS: Venous and arterial forearm vascular responses to incremental intra-arterial doses of ANP, Urodilatin, BNP, CNP, or the ANP receptor antagonist A71915 were studied in 53 patients and 11 controls. ANP receptor antagonism reduced FVV by 4.4%+/-1.2% (P<0.05). The forearm blood flow (FBF) response to ANP was significantly blunted in patients versus controls (P<0.01), whereas FVV increased similarly in both groups (maximum 14.7% and 13.4%, both P<0.001). The eNOS blockade reduced ANP-induced FBF changes in controls but not in patients (P<0.05), whereas similar reductions in FVV changes were seen in groups (both P<0.001). CONCLUSIONS: In cHF venous, but not arterial, ANP responsiveness is preserved. Arterial endothelial dysfunction may contribute to NP resistance.

Comparative efficacy and safety of anticoagulant strategies for acute coronary syndromes. Comprehensive network meta-analysis of 42 randomised trials involving 117,353 patients.

International guidelines differ in strengths of recommendation for anticoagulation strategies in acute coronary syndromes (ACS). We performed a comprehensive network meta-analysis (NMA) of randomised controlled trials (RCTs) to investigate the comparative efficacy and safety of parenteral anticoagulants in ACS. MEDLINE, Cochrane, EMBASE, Google Scholar, major cardiology websites, and abstracts/presentations were searched. Six treatments were identified: 1) unfractionated heparin (UFH) + glycoprotein IIb/IIIa inhibitor (GPI) [UFH+GPI], 2) UFH±GPI, 3) bivalirudin, 4) low-molecular-weight heparins (LMWHs), 5) otamixaban, and 6) fondaparinux. Prespecified outcomes (death, myocardial infarction [MI], revascularisation, major bleeding [MB], minor bleeding, and stent thrombosis [ST]) were evaluated up to 30 days. Forty-two RCTs involving 117,353 patients were included. No significant differences in mortality rates were found among strategies. Compared to UFH+GPI, bivalirudin reduced the odds of MB but increased the odds of ST and MI. LMWHs vs bivalirudin reduced MI risk at the price of MB excess. UFH±GPI significantly increased the odds of MI vs LMWHs, of ST vs UFH+GPI, and of MB vs bivalirudin. Reduced ST risk with otamixaban vs UFH±GPI and vs bivalirudin was offset by a marked 2.5- to four-fold MB excess. Fondaparinux showed an intermediate profile. Results for ST-segment elevation MI were consistent with the overall findings. Early anticoagulant strategies for ACS differ in efficacy and safety, with UFH+GPI and LMWHs reducing ischaemic but increasing bleeding risk, and bivalirudin reducing MB but increases MI and ST. The findings support individualised therapy based on patients' bleeding and ischaemic risks.

Lack of rapid aldosterone effects on forearm resistance vasculature in health.

OBJECTIVES: Systemic infusions of aldosterone cause an acute increase in systemic vascular resistance (SVR) in healthy subjects. It is not clear whether this is due to a direct effect on the vasculature or the result of increased sympathetic tone. We investigated the short-term effects of locally infused aldosterone on the forearm resistance bed. METHODS: In this dose response study, we assessed the effects of incremental doses (10, 50, 100 ng/minute) of intrabrachial aldosterone on forearm blood flow (FBF), using conventional strain gauge plethysmography. Arterial blood pressure was monitored continuously, using finger photo- plethysmography. Forearm vascular resistance (FVR) was calculated. FBF and FVR were also measured in the non-infused arm. Changes in FBF and FVR in the infused arm were corrected for those occurring in the control arm. RESULTS: Plasma aldosterone levels in the venous effluent of the infused arm increased in a dose-dependent fashion, from 113.3+/-17.9 pg/ml at baseline to 297.8+/-51.8 pg/ml at 10 ng/minute (p=<0.01), 743.9+/-105.9 pg/ml at 50 ng/min (p=<0.001 vs. baseline) and 1230.6+/-73.7 pg/ml at 100 ng/min (p=<0.0005 vs. baseline). Plasma concentrations of aldosterone in the control arm did not change significantly vs. baseline. The corrected FBF (+4.1+/-10.3%) and corrected FVR (+4.3+/-11.3%) did not change significantly even at peak infusion rates. CONCLUSIONS: Local intra-arterial infusion of aldosterone had no acute effect on forearm resistance vessels in healthy male volunteers.

Three-layer technique to close a persistent tracheo-oesophageal fistula.

This report of a patient with a persistent tracheo-oesophageal (TE) fistula after removal of a speech valve describes a modification of the technique described by Rosen et al for closing TE. Under local anaesthesia, an incision was made above the stoma edge from 9 o'clock to 3 o'clock. The trachea was separated from the oesophagus to beyond the fistula, and the fistula tract was excised. The oesophageal opening was closed in layers and a local flap rotated from the adjacent sternocleidomastoid muscle and sutured over the oesophageal closure. The trachea was then closed separately.

Lessons from primary PCI practice for the next decade.

Primary percutaneous coronary intervention (PPCI) is the reperfusion treatment of choice for acute ST-elevation myocardial infarction with studies having demonstrated improved outcomes with PPCI over thrombolysis. Its use has increased substantially over the last decade, overtaking thrombolytic therapy in many countries. This has been paralleled with advances in adjunctive technology and pharmacological therapy to further improve outcome, but challenges remain for PPCI practitioners. The evidence behind PPCI is reviewed at every stage of the patient's journey.

Implementing a seventh-order linear multistep method in a predictor-corrector mode or block mode: which is more efficient for the general second order initial value problem.

UNLABELLED: A Seventh-Order Linear Multistep Method (SOLMM) is developed and implemented in both predictor-corrector mode and block mode. The two approaches are compared by measuring their total number of function evaluations and CPU times. The stability property of the method is examined. This SOLMM is also compared with existing methods in the literature using standard numerical examples. AMS SUBJECT CLASSIFICATION: 65L05; 65L06.

Prognostic impact of moderate or severe mitral regurgitation (MR) irrespective of concomitant comorbidities: a retrospective matched cohort study.

OBJECTIVE: We sought to objectively quantify the independent impact of significant mitral regurgitation (MR) on prognosis in patients with multiple comorbidities and ascertain the extent to which median survival is affected by increasing comorbidities. METHODS: This was a retrospective matched cohort study using a clinical-echocardiography reporting database linked to a clinical and administrative database in an Australian tertiary hospital. We identified our study cohort (patients with significant MR) and control cohort (without MR) on transthoracic echocardiographies performed between 2005 and 2010. The main outcome measures were mortality and heart failure rehospitalisation. A Cox proportional hazards model was used to adjust for clinical covariates and the 'win ratio' methodology was utilised to estimate the impact of MR on main outcomes. RESULTS: A total of 218 matched patients with and without significant MR were followed-up for 1 year. Significant MR was associated with an adjusted HR for mortality of 1.83 (95% CI 1.28 to 2.62, p<0.001). The win ratio for death and death or heart failure readmission was 0.57 (95% CI 0.40 to 0.78, p=0.0002) and 0.53 (95% CI 0.39 to 0.71, p<0.0001), respectively. Significant MR with left ventricular (LV) systolic dysfunction and age between 75 and 85 years were associated with a substantial reduction in median survival by 2.3 years. Significant MR with LV systolic dysfunction, age beyond 85 and advance comorbidities were associated with a lesser reduction in median survival by 0.2 years. CONCLUSIONS: Significant MR in patients with multiple comorbidities leads to increase in death and heart failure rehospitalisation with reduced estimated median survival. However, its impact diminishes with increasing comorbidities.

Metabolic manipulation in ischaemic heart disease, a novel approach to treatment.

Antianginal drugs that exert their anti-ischaemic effects primarily by altering myocardial metabolism have recently attracted attention. They have the potential to relieve symptoms in patients with refractory angina who are already on "optimal" medical therapy and have disease that is not amenable to revascularisation, making these drugs an attractive addition to therapy, particularly for the elderly population. In some cases, they may even be used as first-line treatment. These drugs increase glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Whilst they have been demonstrated to reduce ischaemia in several clinical trials, their use remains limited. This review aims to draw attention to these "metabolic" antianginal drugs while surveying the evidence supporting their use and mode of action. Four metabolic antianginal drugs are reviewed: perhexiline, trimetazidine, ranolazine, and etomoxir. We also discuss the metabolic actions of glucose-insulin-potassium and beta-blockers and describe myocardial metabolism during normal and ischaemic conditions. The potential of these metabolic agents may extend beyond the treatment of ischaemia secondary to coronary artery disease. They offer significant promise for the treatment of symptoms occurring due to inoperable aortic stenosis, hypertrophic cardiomyopathy, and chronic heart failure.