Transcatheter Mitral Valve Implantation Systematic Review: Focus on Transseptal Approach and Mitral Annulus Calcification.

INTRODUCTION: This systematic review was performed to evaluate the results of transcatheter mitral valve implantation (TMVI) in the native mitral valve. EVIDENCE ACQUISITION: Medline, EMBASE, and the Cochrane Central register were systematically searched for studies that reported results of TMVI in mitral valve regurgitation and/or stenosis and mitral annular calcification. To improve the sensitivity of the literature search, we performed citation chasing in Google Scholar, Scopus, and Web of Science. EVIDENCE SYNTHESIS: Twelve studies reporting results of TMVI in mitral regurgitation were retrieved and included 347 patients. The transseptal approach represented 28% of cases. Secondary mitral regurgitation was the predominant indication in 63% of cases. Thirty-day mortality was 11% and was lowered with the transseptal approach (7%). Technical success was 92%. Surgical conversion was needed in 5% of patients. Only one patient presented moderate to severe mitral regurgitation. These hemodynamic results were sustainable up to one year of follow-up. Three series focused on results of TMVI in mitral annulus calcification including 167 patients. Only nine patients were treated with TMVI dedicated prosthesis. Eighty-seven patients had their prosthesis delivered through a transseptal approach. Mitral stenosis was present in 63% of cases. Thirty-day mortality was 24%, and none with TMVI prosthesis. Technical success was achieved in 71% of cases and was improved by using TMVI prosthesis (89%). The main complication was left ventricular outflow tract obstruction (20%). Post procedural moderate to severe mitral regurgitation was observed in 4% of cases. CONCLUSION: TMVI seems to be feasible, achieving good technical success and predictable and durable MR reduction.

Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

[Renal denervation a treatment for resistant hypertension: a French experience]. / La dénervation rénale un traitement pour l'hypertension artérielle résistante : expérience française.

Arterial hypertension is the largest single contributor to global mortality, and is poorly controlled in approximately 50% of patients despite lifestyle and pharmacologic interventions. Randomized clinical trials have demonstrated that catheter-based renal sympathetic denervation reduces blood pressure (BP) in patients with resistant hypertension. We sought to evaluate the efficacy of this novel therapy in "Real World" clinical practice. Consecutive patients with treatment-resistant primary hypertension, as defined as home BP>160 mmHg despite treatment with ≥3 antihypertensive drugs, were selected for denervation following renal artery screening. Ambulatory and home BP monitoring was performed in all patients prior to and following percutaneous renal sympathetic denervation. In total, 35 patients were selected for catheter-based renal sympathetic denervation. The mean age was 63.6 ± 11.7 years, 37.1% were women, 37.1% were diabetic, and 11.4% had renal impairment (GFR<45 mL/min). The basal BP (home or ambulatory) was 179.1 ± 20.75/99.66 ± 19.76 mmHg, despite an average of 4.91 ± 0.98 medications per patient. Successful bilateral sympathetic denervation was performed in 33/35 patients (1 renal artery stenosis on angiography [not ablated], 1 patient with renal artery spasm [unilateral denervation]), with an average 5.9 ± 1.6 ablations per renal artery. No procedural complications occurred. At 6 months, blood pressure was 15.5 ± 22.37/87.76 ± 13.97 mmHg (P<0.01). At 2 years follow-up, systolic blood pressure (ABPM or Home BP) was 143.8 ± 15.30 mmHg (P<0.0001) and diastolic 83.42 ± 12.80 mmHg (P=0.0004). There were no adverse events during follow-up, and no deterioration in renal function was observed. Catheter-based renal denervation is safe and efficacious treatment, which results in significant reductions in blood pressure in patients with treatment-resistant hypertension, stable at 2 years follow-up. These results are applicable to real-world patient populations.

Platelet reactivity in type 2 diabetes mellitus: a comparative analysis with survivors of myocardial infarction and the role of glycaemic control.

UNLABELLED: Patients with type 2 diabetes mellitus exhibit considerable platelet dysfunction, though this is poorly characterized in patients with diabetes taking aspirin for the primary prevention of cardiovascular events. We sought to compare platelet function in this patient population with that of a high-risk group of non-diabetic subjects with a history of previous myocardial infarction (MI), and to assess whether glycaemic control impacts on platelet function. METHODS: Platelet aggregation was measured in response to incremental concentrations of five platelet agonists using light transmission aggregometry. All patients were taking aspirin, and aspirin insensitivity was defined as ≥ 20% arachidonic acid (AA) mediated aggregation. Patients with diabetes were divided according to glycaemic control (HbA(1c)): optimal ≤ 6.5, good 6.6-7.4 and suboptimal ≥ 7.5%. RESULTS: In total, 85 patients with type 2 diabetes and 35 non-diabetic patients with previous MI were recruited. Compared to MI patients, diabetes patients had increased aggregation in response to multiple concentrations of epinephrine, collagen, adenosine diphosphate and AA. Aspirin insensitivity was more common in type 2 diabetes (15% vs. 0%, p=0.037). Platelet aggregation was increased in response to several agonists patients with suboptimal glycaemic control compared to patients with optimal control. Aspirin insensitivity was also more common in patients with suboptimal glycaemic control compared to those with good or optimal control (26.0% vs. 8.3% vs. 4%, p=0.04). CONCLUSION: Patients with type 2 diabetes mellitus, without proven vascular disease, exhibit platelet dysfunction and have increased platelet aggregation and aspirin insensitivity compared to non-diabetic patients with previous MI. Platelet dysfunction in diabetes is more severe in patients with suboptimal glycaemic control.

Clopidogrel discontinuation and platelet reactivity following coronary stenting.

AIMS: Antiplatelet therapy with aspirin and clopidogrel is recommended for 1 year after drug-eluting stent (DES) implantation or myocardial infarction. However, the discontinuation of antiplatelet therapy has become an important issue as recent studies have suggested a clustering of ischemic events within 90 days of clopidogrel withdrawal. The objective of this investigation was to explore the hypothesis that there is a transient 'rebound' increase in platelet reactivity within 3 months of clopidogrel discontinuation. METHODS AND RESULTS: In this prospective study, platelet function was assessed in patients taking aspirin and clopidogrel for at least 1 year following DES implantation. Platelet aggregation was measured using a modification of light transmission aggregometry in response to multiple concentrations of adenosine diphosphate (ADP), epinephrine, arachidonic acid, thrombin receptor activating peptide and collagen. Clopidogrel was stopped and platelet function was reassessed 1 week, 1 month and 3 months later. Thirty-two patients on dual antiplatelet therapy were recruited. Discontinuation of clopidogrel increased platelet aggregation to all agonists, except arachidonic acid. Platelet aggregation in response to ADP (2.5, 5, 10, and 20 µm) and epinephrine (5 and 20 µm) was significantly increased at 1 month compared with 3 months following clopidogrel withdrawal. Thus, a transient period of increased platelet reactivity to both ADP and epinephrine was observed 1 month after clopidogrel discontinuation. CONCLUSIONS: This study demonstrates a transient increase in platelet reactivity 1 month after clopidogrel withdrawal. This phenomenon may, in part, explain the known clustering of thrombotic events observed after clopidogrel discontinuation. This observation requires confirmation in larger populations.

Multivessel percutaneous coronary intervention: a review of the literature and fallacies in its interpretation.

Since its inception in the 1960s, coronary revascularization has established itself as a fundamental therapy for treating the acute and chronic manifestations of atherosclerotic coronary disease. Catheter-based techniques were realized in the late 1970s and have evolved from balloon dilatation of simple, discrete stenoses to complex, multivessel interventions across the spectrum of coronary disease presentations. In retrospect, there were two defining technological developments the introduction of coronary stenting which enabled more stable acute outcomes and the evolution of drug-eluting stents which ameliorated the effect of neointimal hyperplasia the dominant cause of delayed loss of efficacy. The role of catheter-based intervention in multivessel disease is well established in the treatment of ST-elevation myocardial infarction and acute coronary syndromes. On the contrary, in the arena of in stable coronary disease, its utility is keenly debated. The pace of development in cardiovascular pharmacology has rendered early investigation of best treatment strategies largely obsolete, while newer revascularization techniques have successfully extended the remit of catheter-based multivessel intervention strategies to include left main stem disease, bifurcation stenosis and chronic occlusions. Consequently complete revascularization is now available via a percutaneous approach and conventional beliefs relating to choice of revascularization strategy deserve re-assessment. The authors present a contemporary review of the literature and a challenge against fallacies in its interpretation.

Lipid lowering targets are easier to attain than those for treatment of hypertension in type 2 diabetes.

AIM: To assess the impact of therapeutic strategies to reduce cardiovascular risk in patients with type 2 diabetes. METHODS: Five-hundred patients with type 2 diabetes were studied, using retrospective case note analysis in 1997 (followed by a unit policy targeting vascular risk) and again in 2001. RESULTS: The mean BP of the hypertensive patients was unchanged, 151/83 +/- 23/12 mmHg (1997) and 149/84 +/- 19.1/9.8 mmHg (P=0.2) (2001) (despite increase in patients receiving 23 antihypertensives (4.2% to 18.0%, P<0.01). The mean cholesterol improved from 5.34 +/- 1.1 mmol/L to 4.72 +/- 0.94 mmol/L (P<0.01). 2.9% compared with 44.6% (P<0.01) of hypercholesterolaemic patients, achieved target cholesterol. Antiplatelet therapy increased from 27.6% to 61.2% (P<0.01). Reduced mean HbA1c, 7.91 +/- 1.61% to 7.12 +/- 1.41% (P<0.01). CONCLUSION: Improved lipid profiles, aspirin uptake and glycaemic control, but no improvement in blood pressure targets were achieved. Additional strategies are required to achieve cardiovascular risk factor targets.

Expression of the K54 and O4 specific antigen has opposite effects on the bactericidal activity of squalamine against an extraintestinal isolate of Escherichia coli.

Squalamine is a novel cationic steroid that possesses potent, broad spectrum, antimicrobial activity. Recent data suggests that squalamine or related compounds may be present and important in host resistance to infection in the urinary tract. Therefore, the role of the K54 capsule and the O4 specific antigen moiety of the lipopolysaccharide in protecting an extraintestinal isolate of Escherichia coli against the bactericidal activity of this novel antimicrobial compound was studied. The O4 specific antigen was important for protection against squalamine. Surprisingly, in contrast, the presence of the K54 antigen enhanced the bactericidal activity of squalamine. This is the first example, to our knowledge, in which an established virulence trait, the K54 capsule, may be detrimental to an infecting pathogen under certain circumstances.