CRT-100.04 Delaying Reperfusion Plus LV Unloading Reduces Infarct Size: A Per-Protocol-Analysis of the STEMI_DTU Pilot Study

Background: Myocardial infarct size (IS) and microvascular obstruction (MVO) are well-established prognostic markers in STEMI. The STEMI-DTU pilot trial was the first exploratory study to identify that LV unloading and delayed reperfusion was feasible. We now report new findings in patients from per-protocol cohort on the basis of magnitude of sum of precordial ST-segment elevation. Method: In a multicenter, prospective, randomized safety and feasibility trial, 50 patients with anterior STEMI to LV unloading using Impella CP were assigned into two different arms including immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). Cardiac magnetic resonance (CMR) imaging assessed infarct size normalized to the area at risk (IS/AAR) 3-5 days after PCI. Patients without CMR at 3-5 days, without PCI of a culprit LAD lesion and without STEMI were not per-protocol and thus excluded from this analysis. Results: 32 patients meeting all inclusion and exclusion criteria (U-IR,n=15; U-DR,n=17) were included in our analysis. Despite longer symptom-to-balloon times in the U-DR arm, IS/AAR was significantly lower with 30 minutes of delay to reperfusion in the presence of active LV unloading (47±16% vs 60±15%, p=0.02) and remained lower irrespective of the magnitude of precordial ΣSTE (Figure 1). MVO was not significantly different between groups (1.5±2.8% vs 3.5±4.8%,p=0.15), but significantly lower in the U-DR arm among patients with precordial ΣSTE≥8mm (1.5±2.5% vs 5.6±5.3%, p=0.04). Conclusion: This analysis supports the paradigm-changing concept that when treated per protocol, 30 minutes of delay to reperfusion with active LV unloading may reduce infarct size irrespective of precordial STE magnitude. Ongoing STEMI-DTU Pivotal trial will provide us further information on these findings

Comparative effects of verapamil and nitroprusside on left ventricular function in patients with hypertension

AbstractThe effects of verapamil were compared with those of nitroprusside at matched mean arterial pressures and heart rates in 10 symptomatic hypertensive patients during cardiac catheterization. Simultaneous radionuclide angiography and micromanometer pressure measurements were obtained to assess left ventricular pressure-volume relations. Compared with control conditions, verapamil increased left ventricular end-diastolic volume index from 57 ± 16 to 70 ± 28 ml/m2 (p = 0.05) without a significant increase in left ventricular end-diastolic pressure (from 10 ± 4 to 13 ± 6 mm Hg). Despite a downward and rightward shift in the end-systolic pressure-volume relation indicating negative inotropic effects, ejection fraction did not decrease significantly (from 52 ± 9% to 46 ± 9%); cardiac index and stroke volume index remained unchanged. The change in stroke volume index with verapamil was directly related to the magnitude of change in end-diastolic volume index (r = 0.82, p < 0.005), suggesting that the increase in enddiastolic volume did not arise purely from negative inotropic effects. Systemic vascular resistance index decreased from 42 ± 8 to 34 ± 7 mm Hg-min-m2/liter (p < 0.05).In contrast, nitroprusside decreased left ventricular end-diastolic volume index from 57 ± 16 to 41 ± 10 ml/m2 (p < 0.05), cardiac index from 3.2 ± 0.7 to 2.8 ± 0.6 liters/min per m2 (p < 0.05) and stroke volume index from 28 ± 6 to 24 ± 5 ml/m2 (p < 0.01), with no change in systemic vascular resistance index (40 ± 10 mm Hg·min·m2). The end-systolic pressure-volume relation shifted downward and leftward in all patients, stemming from altered left ventricular loading.Thus, in equihypotensive doses, verapamil and nitroprusside have markedly different effects on left ventricular function. The peripheral vasodilation and apparent improvement in left ventricular filling during verapamil balanced the negative inotropic effects, resulting in maintenance of stroke volume and cardiac index. The primary hypotensive effect of verapamil was a decrease in systemic vascular resistance, whereas that of nitroprusside was a decrease in cardiac index stemming from reduced left ventricular preload

Dual Vasopressin Receptor Antagonism to Improve Congestion in Patients With Acute Heart Failure:Design of the AVANTI Trial

Background: Loop diuretics are the main treatment for patients with acute heart failure, but are associated with neurohormonal stimulation and worsening renal function and do not improve long-term outcomes. Antagonists to arginine vasopressin may provide an alternative strategy to avoid these effects. The AVANTI study will investigate the efficacy and safety of pecavaptan, a novel, balanced dual-acting V1a/V2 vasopressin antagonist, both as adjunctive therapy to loop diuretics after admission for acute heart failure, and later as monotherapy. Methods and Results: AVANTI is a double-blind, randomized phase II study in 571 patients hospitalized with acute heart failure and signs of persistent congestion before discharge. In part A, patients will receive either pecavaptan 30 mg/d or placebo with standard of care for 30 days. In part B, eligible patients will continue treatment or receive pecavaptan or diuretics as monotherapy for another 30 days. The primary end points for part A are changes in body weight and serum creatinine; for part B, changes in body weight and blood urea nitrogen/creatinine ratio. Conclusions: This study will provide the first evidence that a balanced V1a/V2 antagonist may safely enhance decongestion, both as an adjunct to loop diuretics and as an alternative strategy

Response to Letter Regarding Article, "Hypertrophic Cardiomyopathy Is Predominantly a Disease of Left Ventricular Outflow Tract Obstruction"

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