Search

Background: In ST-segment–elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. Methods: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. Results: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P =0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P =0.53). Conclusions: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.

Aim This executive summary of the hypertrophic cardiomyopathy clinical practice guideline provides recommendations and algorithms for clinicians to diagnose and manage hypertrophic cardiomyopathy in adult and pediatric patients as well as supporting documentation to encourage their use. Methods A comprehensive literature search was conducted from January 1, 2010, to April 30, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Structure Many recommendations from the earlier hypertrophic cardiomyopathy guidelines have been updated with new evidence or a better understanding of earlier evidence. This summary operationalizes the recommendations from the full guideline and presents a combination of diagnostic work-up, genetic and family screening, risk stratification approaches, lifestyle modifications, surgical and catheter interventions, and medications that constitute components of guideline directed medical therapy. For both guideline-directed medical therapy and other recommended drug treatment regimens, the reader is advised to follow dosing, contraindications and drug-drug interactions based on product insert materials.

Background— Thrombin-dependent platelet activation is heightened in the setting of percutaneous coronary intervention and may cause arterial thrombosis with consequent myocardial necrosis. Given the high incidence of adverse effects in patients with acute coronary syndromes, there remains an unmet need for the development of new therapeutics that target platelet activation without unduly affecting hemostasis. The thrombin receptor, PAR1, has recently emerged as a promising new target for therapeutic intervention in patients with acute coronary syndromes. Methods and Results— We report the development of a first-in-class intracellular PAR1 inhibitor with optimized pharmacokinetic properties for use during percutaneous coronary intervention in patients with acute coronary syndromes. PZ-128 is a cell-penetrating pepducin inhibitor of PAR1 that targets the receptor–G-protein interface on the inside surface of platelets. The structure of PZ-128 closely resembles the predicted off-state of the corresponding juxtamembrane region of the third intracellular loop of PAR1. The onset of action of PZ-128 was rapid and suppressed PAR1 aggregation and arterial thrombosis in guinea pigs and baboons and strongly synergized with oral clopidogrel. There was full recovery of platelet function by 24 hours. Importantly, PZ-128 had no effect on bleeding or coagulation parameters in primates or in blood from patients undergoing percutaneous coronary intervention. Conclusions— Based on the efficacy data in nonhuman primates with no noted adverse effects on hemostasis, we anticipate that the rapid onset of platelet inhibition and reversible properties of PZ-128 are well suited to the acute interventional setting of percutaneous coronary intervention and may provide an alternative to long-acting small-molecule inhibitors of PAR1.

Coronary stenting has become the dominant therapy for patients referred for coronary revascularization. Because of their documented efficacy in reducing in-stent restenosis (ISR),1–3 drug-eluting stents (DES) are used for this purpose in most percutaneous revascularization procedures. Although intended primarily for use in native, de novo stenoses in coronary vessels 2.5 to 3.5 mm in diameter, DES currently are implanted in a diverse array of patients and lesions, including total occlusions, large and small vessels, acute myocardial infarction, and saphenous vein grafts, despite the absence of convincing trial efficacy data in some of these circumstances. Article p 645 Despite the growing perception by cardiac interventionalists of their ability to percutaneously address increasingly complex patient subsets, the diseased left main coronary artery (LM) generally has been regarded as the exclusive purview of the cardiac surgeon. This rationale has centered around older trials documenting enhanced survival and reduced symptoms in surgically treated symptomatic patients with LM disease compared with patients randomized to medical therapy, which generally did not include percutaneous coronary intervention (PCI).4 Surgical referral of symptomatic patients with LM disease was subsequently corroborated by results from interventional studies in the balloon angioplasty and bare metal stenting eras.5,6 Retrospective analysis of data from the Unprotected Left Main Trunk Investigation Multicenter Assessment (ULTIMA) registry suggested that unprotected LM stenting might be successfully performed if guided by a simple patient risk stratification, limiting treatment to younger individuals not exhibiting shock who have relatively preserved left ventricular systolic function.6 Given the deliverability and low restenosis rates of currently available DES, the plausibility of percutaneous therapy targeting unprotected LM stenoses has resurfaced and has initially been addressed in a series of single-center reports and collected registries, most of which suggest improved outcomes compared with bare metal stents7,8 and acceptable results when contrasted …

Case Presentation : A 58-year-old diabetic man was referred for severe progressive exertional dyspnea consistent with New York Heart Association (NYHA) functional class III. Six years earlier, he underwent coronary artery bypass grafting, complicated by a sternal wound infection. Physical examination was notable for a bifid carotid pulse and loud apical systolic ejection murmur. Echocardiography documented hyperdynamic left ventricular (LV) systolic function and asymmetric hypertrophy confined to the basal ventricular septum (measuring 20 mm in thickness) consistent with hypertrophic cardiomyopathy (HCM). Continuous wave Doppler estimated a 65 mm Hg subaortic gradient due to dynamic systolic anterior motion of the mitral valve with septal contact. Coronary angiography showed patent bypass grafts. Medical management with β-blockers and verapamil was ineffective in controlling symptoms. Catheter-based intervention was considered for this patient to reduce outflow obstruction and symptoms. HCM is a relatively common genetic disease with important clinical consequences, including sudden death in the young and disability due to heart failure at any age.1,2 It is estimated that progression to NYHA functional classes III/IV associated with obstruction to LV outflow occurs in about 10% of HCM patients who are limited largely by exertional dyspnea, chest pain, fatigue, and occasionally orthopnea or nocturnal dyspnea.1,2 Long-term consequences of HCM attributable to outflow obstruction have been emphasized, particularly progression of disabling symptoms and death related to heart failure.2 The traditional first line of therapy to improve quality of life in HCM patients with symptoms and outflow obstruction has been administration of negative inotropic agents, including β-blockers, verapamil, and disopyramide.1,2 Although symptoms can be controlled by drug treatment, a small minority of patients may become disabled and refractory to maximum medical management, and consequently eligible for major therapeutic interventions that target relief of obstruction and mitral regurgitation.1 Historically, this strategy has been confined …

Background— Epidemiology data for lower-extremity arterial thromboembolism (LET) are limited and may result from either acute limb ischemia or an acute exacerbation of critical limb ischemia. Given marked changes in both diagnosis and therapy over the last 2 decades, we hypothesized that this time period would have witnessed reductions in both the incidence and in-hospital mortality of LET. Methods and Results— Data from 1988 through 2007 from the National Hospital Discharge Survey were analyzed. All admissions for patients with LET were extracted, and the respective International Classification of Diseases, Ninth Revision, Clinical Modification codes were internally validated for both LET and acute limb ischemia. Descriptive statistics were used. The validity of the codes was good for identifying LET cases but poor for identifying acute limb ischemia cases because many of these acute presentations were attributable to critical limb ischemia. Over the 20-year span, there were 1.76 million cases of LET. The incidence of LET decreased significantly from 42.4 per 100 000 persons between 1988 and 1997 to 23.3 per 100 000 persons between 1998 and 2007. The in-hospital mortality for LET decreased significantly from 8.28% between 1988 and 1997 to 6.34% between 1998 and 2007, and male patients achieved greater mortality reduction compared with female patients. Treatments for acute limb ischemia showed decreasing use of surgical bypass and amputation and increasing rates of catheter-based thrombolysis. Conclusions— Over the 20-year study period, there have been significant reductions in both LET incidence and in-hospital mortality. Unfortunately, LET admissions extracted from an administrative database comprise a diverse group of individuals, including those with acute and chronic forms of limb ischemia and iatrogenic arterial injury, limiting the true assessment of ALI incidence.

Apreviously healthy 65-year-old woman presented with palpitations and positional chest discomfort 3 weeks after she sustained chest wall trauma in a motor vehicle accident. Physical examination revealed occasional premature ventricular beats and low-grade fever. Her erythrocyte sedimentation rate was elevated (66 mm/h). Transthoracic and transesophageal echocardiography revealed a 3×3-cm, well-demarcated, homogeneous, round mass moving with the heart adjacent to the right atrium (Figures 1A, B). There was invagination of nearby cardiac chambers but no obstruction to right heart filling. MRI showed a circumscribed mass with dense tissue characterization (isointense to myocardium) not consistent with blood or fat (Figure 2A). There was minimal enhancement of the mass after gadolinium injection. Coronary angiography was normal. Two weeks later, …

Background— Several trials support the usefulness of disease management (DM) for improving clinical outcomes in heart failure (HF). Most of these studies are limited by small sample size; absence of concurrent, randomized controls; limited follow-up; restriction to urban academic centers; and low baseline use of effective medications. Methods and Results— We performed a prospective, randomized assessment of the effectiveness of HF DM delivered for 90 days across a diverse provider network in a heterogeneous population of 200 patients with high baseline use of approved HF pharmacotherapy. During a 90-day follow-up, patients randomized to DM experienced fewer hospitalizations for HF [primary end point, 0.55±0.15 per patient-year alive versus 1.14±0.22 per patient-year alive in control subjects; relative risk (RR), 0.48, P =0.027]. Intervention patients experienced reductions in hospital days related to a primary diagnosis of HF (4.3±0.4 versus 7.8±0.6 days hospitalized per patient-year; RR, 0.54; P P =0.043), and days in hospital per patient-year alive for cardiovascular cause (RR, 0.64; P Conclusions— In a population with high background use of standard HF therapy, a DM intervention, uniformly delivered across varied clinical sites, produced significant short-term improvement in HF-related clinical outcomes. Longer-term benefit likely requires more active chronic intervention, even among patients who appear clinically stable.