Long-term outcomes associated with the transaortic approach to transcatheter Aortic valve replacement.

OBJECTIVE: We investigated the long-term safety, efficacy and clinical outcomes associated with transaortic (TAO) transcatheter aortic valve replacement (TAVR) in the United States. BACKGROUND: We previously reported the technical feasibility and short-term safety of TAO TAVR. Compared to transapical (TAP) access, the TAO approach was associated with shorter median intensive care unit (ICU) length of stay (LOS) and more favorable technical learning curve. However, outcomes data beyond 30 days were lacking and the longer-term clinical consequences of this strategy were unknown. METHODS: Mortality outcomes at 1 year (and longer) of 44 consecutive patients who underwent TAO TAVR in our institution were compared with that of 76 consecutive patients who underwent TAP TAVR at our site. Risk-adjusted analysis was performed in propensity-matched patients (25 from each group) to account for baseline differences. RESULTS: TAO TAVR was associated with a trend towards lower all-cause mortality at 1 year compared to TAP TAVR (18% vs. 34%, P=0.09 in the overall sample; 12% vs. 40%, P=0.05 in the matched cohort). The higher probability of survival with TAO TAVR persisted after a median follow-up period of 23 months (hazard ratio [HR]=1.96, P=0.06 in the overall sample; HR=3.4, P=0.01 in the matched cohort). Cardiovascular mortality at 1 year was lower with TAO TAVR (2% vs. 22%, P=0.01 in the overall sample; 4% vs. 28%, P=0.05 in the matched cohort). ICU LOS (shorter in the TAO group) and implantation of second prosthetic valve (higher incidence in the TAP group) were independent predictors of long-term mortality. CONCLUSION: The outcomes associated with TAO TAVR compare favorably with TAP TAVR. Our results appear to corroborate the long-term safety and efficacy of the TAO approach in TAVR patients with inadequate iliofemoral access.

Clinical outcomes with on-label and off-label use of the transcatheter heart valve in the United States.

OBJECTIVE: We explored the efficacy, safety, and clinical consequences of on-label and off-label transcatheter aortic valve replacement (TAVR) in the real-world setting. BACKGROUND: The transcatheter heart valve (THV) was initially approved only for transfemoral (TF) delivery (on-label use) during TAVR in inoperable patients with severe aortic stenosis (AS). Because of lack of alternative options in TAVR-eligible patients with inadequate TF access, other routes have been utilized for THV implantation (off-label use), outcomes of which were previously unknown. METHODS: Consecutive patients with severe inoperable AS who underwent clinical TAVR at our site were enrolled in a prospective database. Fifty subjects underwent TF-TAVR (on-label group), while non-TF routes were utilized in 60 subjects (off-label group). Procedural events, 30-day clinical outcomes, and 1-year all-cause mortality data were analyzed. RESULTS: Technical device success was similar between on-label and off-label groups (88% vs. 87%, respectively; P = 0.92), as was the incidence of procedural complications and 30-day clinical events. The on-label group had lower 1-year all-cause death rate (12%) compared to the off-label group (32%; P = 0.02). The 1-year all-cause mortality in the off-label group was comparable to published clinical trial and registry data on TAVR, and appeared lower than historical outcomes with conservative medical therapy. CONCLUSION: On-label use of the THV in the real-world setting was associated with favorable survival outcomes compared to off-label TAVR and historical data. Off-label use of the THV appeared to be safe and effective when used in select patients with inoperable AS who are not eligible for TAVR via TF approach.

The anti-ischemic and anti-anginal properties of statins.

Angina pectoris resulting from myocardial ischemia afflicts half of all patients with coronary heart disease (CHD). Chronic angina remains a major public health burden despite state-of-the-art therapies, and improvement in survival from myocardial infarction and CHD has only increased its prevalence. There is growing experimental and clinical evidence pointing to the anti-ischemic and anti-anginal properties of statins. Some data suggest that the degree of anti-ischemic efficacy of statins may be comparable to the current standard pharmacologic and mechanical strategies. The pleiotropic effects of statins are postulated to be primarily responsible for their anti-ischemic and anti-anginal properties. These include improvement of endothelial function, enhancement of the ischemic vasodilatory response, modulation of inflammation, and protection from ischemia-reperfusion injury. The anti-ischemic effects of statins further strengthen their role as a crucial component of the optimal medical therapy for CHD.

Acute myocardial infarction and the five-chambered heart.

The case of a patient presenting with acute inferior ST-elevation myocardial infarction is described. Emergent coronary angiography of the right coronary artery revealed what appeared to be the abrupt drainage of contrast into a large, peculiar cavity or chamber. Echocardiography and cardiac computed tomography demonstrated a giant right coronary aneurysm in the right coronary artery that gave the impression of a "fifth heart chamber." The patient underwent successful surgical resection of the aneurysm. Diagnostic and treatment approaches to giant coronary aneurysms are discussed.

The role of renin-angiotensin agents in altering the natural history of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease (CVD) morbidity and mortality worldwide. Renin-angiotensin system (RAS) blockers have been indispensable in diminishing the macrovascular and microvascular complications of diabetes. In addition, cumulative evidence from retrospective studies pointed toward a beneficial effect of RAS agents in preventing the development and progression of T2DM. This disease-modifying potential of RAS blockers has been substantiated by recent prospective trials. Contemporary concepts regarding the natural history of T2DM and the pathophysiologic processes involved have increased our understanding of the mechanisms underlying the therapeutic potential of these agents in diabetes management. In addition to their established roles in the primary prevention of CVD in patients with diabetes, RAS blockers might be considered a suitable therapeutic choice for preventing the development of frank diabetes in high-risk patients.

The current state of beta blockers in hypertension therapy.

Beta adrenergic blockers have had a long history as frontline agents in hypertension therapy. They are the mainstay of treatment in ischemic heart disease, heart failure, high risk coronary artery disease and arrhythmias, as their importance in these compelling indications are well-established. However, the efficacy and relevance of beta blockers in the treatment of uncomplicated hypertension have been questioned because the traditional agents were deemed not atpar with drugs from other classes in terms of cardiovascular outcomes. Although atenolol and other traditional agent s have lost favor, the other cardioselective agents have been shown to be at least as efficacious in hypertension as the other classes of drugs. Their use in hypertension therapy should continue, especially in young and diabetic individuals where high sympathetic tone and high renin levels are the primary features. The newer-generation vasodilating beta blockers have favorable hemodynamic and metabolic properties, better side effect profile and improved efficacy in treating uncomplicated hypertension. With the advent of these new agents, the beta blocker class should remain as a viable first-line option in antihypertensive therapy.

Oral midodrine is effective for the treatment of hypotension associated with carotid artery stenting.

Hypotension is commonly encountered during carotid artery stenting (CAS), mediated by vagal stimulation and suppression of sympathetic outflow. Some patients require treatment with intravenous vasopressors (dopamine, nor-epinephrine, or phenylephrine). The authors describe the successful use of the oral agent midodrine as an alternative to intravenous vasopressors in the treatment of hypotension related to CAS. Of 55 patients who underwent elective CAS, 19 (35%) experienced significant hypotension, and 15 (27%) required vasopressor therapy. Eleven patients received intravenous dopamine infusion in an intensive care setting, whereas 4 received oral midodrine in a regular telemetry unit. All patients eventually recovered and were discharged without any residual cardiovascular or neurological complications. No major side effects were noted with the use of both dopamine and midodrine. Cost of hospitalization was significantly higher in the dopamine group because of the need for ICU admission.

Transradial approach to endovascular Infrarenal aortic repair.

Atherosclerotic disease of the abdominal aorta is relatively common. However chronic stenosis of the infrarenal aorta is a fairly rare condition that has been traditionally treated with open endarterectomy and aorto-bifemoral bypass surgery. These surgeries may be associated with a significant increase in mortality and morbidity. Using 2 case examples we describe the feasibility of endovascular treatment of severely calcified infra-abdominal aortic lesion using a transradial endovascular approach that greatly reduce both vascular and access site complications.

Primary Prevention of Atrial Fibrillation - The Path Untread.

The prevalence and incidence of atrial fibrillation (AF) is on the rapid rise. To slow down the AF epidemic, effective primary prevention strategies need to be instituted. Unfortunately, this is an area that has not been well-explored. There is a multitude of risk factors that predispose to the development of AF. Of these, the most common from an epidemiologic perspective are advanced age, hypertension, diabetes, ischemic heart disease, and heart failure. The first-line pharmacologic therapies for these predisposing conditions (e.g. beta blockers, renin-angiotensin system inhibitors, statins, and omega-3 fatty acids) appear to also have potential roles in the primary prevention of AF. Definitive data, however, is lacking as to efficacy of these drugs for this particular purpose. Large-scale, high-quality randomized clinical trials on AF primary preventive strategies are urgently required in order to guide clinical practice. For now, adherence to the guideline-based therapies of each individual risk factor appears to be the most reasonable approach for the primary prevention of AF.

The transaortic approach for transcatheter aortic valve replacement: initial clinical experience in the United States.

OBJECTIVES: This study sought to investigate the technical feasibility and safety of the transaortic (TAO) transcatheter aortic valve replacement (TAVR) approach in patients not eligible for transfemoral (TF) access by using a device commercially available in the United States. BACKGROUND: A large proportion of candidates for TAVR have inadequate iliofemoral vessels for TF access. The transapical route (TAP) is the current alternative but is associated with less favorable outcomes. Other access options need to be explored. METHODS: Forty-four consecutive patients with inoperable, severe aortic stenosis underwent TAO TAVR in our institution. Procedural and 30-day clinical outcomes data were compared with data from 76 consecutive patients who underwent TAP TAVR at our site. Technical learning curves were assessed by comparing outcomes of the first 20 cases with the subsequent patients who underwent each procedure. RESULTS: The TAO and TAP TAVR groups were similar in terms of device success according to Valve Academic Research Consortium criteria (89% vs. 84%; p = 0.59) and rates of the 30-day combined safety endpoint of all-cause mortality, myocardial infarction, major stroke, disabling bleeding, severe acute kidney injury, and valve reintervention (20% vs. 33%; p = 0.21). The TAO approach, compared with TAP TAVR, was associated with lower combined bleeding and vascular event rate (27% vs. 46%; p = 0.05), shorter median intensive care unit length of stay (3 vs. 6 days; p = 0.01), and a favorable learning curve. CONCLUSIONS: TAVR via the TAO approach is technically feasible, seems to be associated with favorable outcomes, and expands the current alternative options for access sites in patients with inoperable aortic stenosis who are ineligible for TF TAVR.

Atrial fibrillation in heart failure.

Heart failure (HF) and atrial fibrillation (AF) are highly prevalent debilitating conditions that often coexist and are frequently encountered in clinical practice. The presence of chronic AF is a marker of worse prognosis in patients with HF, and the onset of new AF in those with chronic HF is associated with increased morbidity and mortality. Advances in the development of novel drugs, nonpharmacologic modalities, and therapeutic strategies, as well the increased understanding of the pathobiology of HF and AF, are key to mitigating the tremendous public health burden that is associated with these conditions.

Intra-graft abciximab and verapamil combined with direct stenting is a safe and effective strategy to prevent slow-flow and no-reflow phenomenon in saphenous vein graft lesions not associated with thrombus.

UNLABELLED: Slow flow and no-reflow phenomenon (SF-NR) in saphenous vein grafts (SVG) stenting is related to the occurrence of distal plaque embolization, platelet activation and microvascular vasospasm. Our article discusses few of the patents related to strategies for preventing slow-flow/no-reflow phenomenon in SVG percutaneous coronary intervention (SVG PCI). METHODS: Data from 163 consecutive patients who underwent PCI of SVG lesions without visible macro-thrombus without use of distal embolic protection device over a 10-year period were reviewed. Patients in the novel strategy group received prophylactic intra-graft administration of abciximab and verapamil followed by direct stenting (n=91). The control group (n=72) comprised of patients who had undergone conventional PCI technique before the routine availability of distal embolic protection devices, with balloon pre-dilatation of the target lesion followed by stent deployment and optional use of intragraft verapamil or intravenous abciximab. Patients with visible macro-thrombus in the vein graft were excluded from the study, since these patients underwent PCI with use of the distal embolic protection (filter). RESULTS: SF-NR (TIMI 0-1 flow) occurred more frequently in the control group compared to the novel strategy group (18% vs. 1%, P=0.0001). One patient in the control group died after developing persistent SF-NR and acute MI post-PCI. No death was reported in the novel strategy group. In the control group, 13% patients developed cardiac enzyme elevation 3 times more than normal after the PCI as compared to 1% in the novel strategy group (P < 0.05). CONCLUSIONS: In recent years several distal embolic protection devices have been granted patents for minimizing the chance of slow-flow/no-reflow phenomenon. In carefully selected subgroup of SVG lesions without visible macrothrombus, a strategy of prophylactic intra-graft administration of abciximab and verapamil, combined with direct stenting of the graft lesion without pre-dilatation, can be safely accomplished without any significant risk of slow-flow/no-reflow phenomenon. We propose a patent to this 3-step strategy of percutaneous coronary intervention of SVG lesions not associated with thrombus.

Lipid-lowering therapy with statins for the primary and secondary prevention of cardiovascular disease.

Cardiovascular disease (CVD) still ranks as the top cause of mortality worldwide. Lipid-modifying therapy has revolutionized the treatment of the disease and is partly responsible for the recent decline in deaths due to CVD. Treatment strategies have evolved since the introduction of the earlier lipid-lowering agents (fibrates, niacin, bile acid resins) to the advent of statins, which have become the standard drugs in cholesterol therapy. The strategy of using high-intensity statin therapy as the initial treatment approach in high-risk individuals, rather than focusing on specific cholesterol levels alone, remains a subject of debate.

Benefits of statin therapy and compliance in high risk cardiovascular patients.

Cardiovascular disease (CVD) remains the top cause of global mortality. There is considerable evidence that supports the mortality and morbidity benefit of statin therapy in coronary heart disease (CHD) and stroke, both in primary and secondary prevention settings. Data also exist pointing to the advantage of statin treatment in other high-risk CVD conditions, such as diabetes, CKD, CHF, and PVD. National and international clinical guidelines in the management of these CVD conditions all advocate for the utilization of statin therapy in appropriate patients. However, overall compliance to statin therapy remains suboptimal. Patient-, physician-, and economic-related factors all play a role. These factors need to be considered in devising approaches to enhance adherence to guideline-based therapies. To fully reap the benefits of statin therapy, interventions which improve long-term treatment compliance in real-world settings should be encouraged.

Atrial fibrillation in heart failure: a comprehensive review.

Chronic heart failure and atrial fibrillation are 2 major disorders that are closely linked. Their coexistence is associated with adverse prognosis. Both share several common predisposing conditions, but their interaction involves complex ultrastructural, electrophysiologic, and neurohormonal processes that go beyond mere sharing of mutual risk factors. Rate control approach remains the standard therapy for atrial fibrillation in heart failure because current strategies at rhythm control have so far failed to positively impact mortality and morbidity. This is largely because of the shortcomings of current pharmacologic anti-arrhythmic agents. Surgical and catheter-based therapies are promising, but long-term data are lacking. The role of non-anti-arrhythmic therapeutic agents also is being explored. Further progress toward improved understanding the complex relationship between atrial fibrillation and heart failure should improve management strategies.

The balance between anti-ischemic efficacy and bleeding risk of antithrombotic therapy in percutaneous coronary intervention: a Yin-Yang paradigm.

BACKGROUND: The development of newer and more potent antithrombotic agents and strategies has markedly reduced cardiovascular mortality and ischemic complications in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). With every approach to reduce coronary thrombosis, however, there is an accompanying risk of increasing bleeding complications elsewhere. Conversely, reducing bleeding complications may increase coronary thrombotic (ischemic) events. This is the Yin-Yang principle of antithrombotic therapy and strategies in PCI. Balancing both ends of the spectrum is essential, and an individualized approach to therapy is advocated. This article reviews the efficacy and bleeding risk profile of the different antithrombotic agents and strategies in PCI, including aspirin, thienopyridines, glycoprotein IIb/IIIa-inhibitors, heparin-based antithrombins, synthetic antithrombins and oral anticoagulants. Recommendations for reducing thrombotic and bleeding complications are also discussed.