Inotrope versus placebo therapy in cardiogenic shock: Rationale and study design of the CAPITAL DOREMI2 trial.

BACKGROUND: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS. METHODS AND DESIGN: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge. IMPLICATION: This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients.

Revisiting the Evidence for Dipyridamole in Reducing Restenosis: A Systematic Review and Meta-analysis.

ABSTRACT: Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion-an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7-3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40-0.70], I2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences -1.13 (95% CI -1.74 to -0.53), I2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67-0.88), I2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization.

Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial.

BACKGROUND: Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS. METHODS: Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters. RESULTS: Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73-1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18-0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization. CONCLUSIONS: BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165.

Journal Initiatives to Enhance Preclinical Research: Analyses of Stroke, Nature Medicine, Science Translational Medicine.

Background and Purpose- Preclinical research using animals often informs clinical trials. However, its value is dependent on its scientific validity and reproducibility, which are, in turn, dependent on rigorous study design and reporting. In 2011, Stroke introduced a Basic Science Checklist to enhance the reporting and methodology of its preclinical studies. Except for Nature and Science journals, few others have implemented similar initiatives. We sought to estimate the impact of these journal interventions on the quality of their published reports. Methods- All articles published in Stroke, Nature Medicine, and Science Translational Medicine over 9 to 18 years and in 2 control journals without analogous interventions over a corresponding 11.5 years were reviewed to identify reports of experiments in nonhuman mammals with proposed clinical relevance. The effect of journal interventions on the reporting and use of key study design elements was estimated via interrupted time-series analyses. Results- Of 33 009 articles screened, 4162 studies met inclusion criteria. In the 3.5 to 12 years preceding each journal's intervention, the proportions of studies reporting and using key study design elements were stable except for blinding in Stroke and randomization in Science Translational Medicine, which were both increasing. Post-intervention, abrupt and often marked increases were seen in the reporting of randomization status (level change: +17% to +44%, P≤0.005), blinding (level change: +20% to +40%, P≤0.008), and sample size estimation (level change: 0% to +40%, P≤0.002 in 2 journals). Significant but more modest improvements in the use of these study design elements were also observed. These improvements were not seen in control journals. Conclusions- Journal interventions such as Stroke's author submission checklist can meaningfully improve the quality of published preclinical research and should be considered to enhance study transparency and design. However, such interventions are alone insufficient to fully address widespread shortcomings in preclinical research practices.

Methodological Rigor in Preclinical Cardiovascular Studies: Targets to Enhance Reproducibility and Promote Research Translation.

RATIONALE: Methodological sources of bias and suboptimal reporting contribute to irreproducibility in preclinical science and may negatively affect research translation. Randomization, blinding, sample size estimation, and considering sex as a biological variable are deemed crucial study design elements to maximize the quality and predictive value of preclinical experiments. OBJECTIVE: To examine the prevalence and temporal patterns of recommended study design element implementation in preclinical cardiovascular research. METHODS AND RESULTS: All articles published over a 10-year period in 5 leading cardiovascular journals were reviewed. Reports of in vivo experiments in nonhuman mammals describing pathophysiology, genetics, or therapeutic interventions relevant to specific cardiovascular disorders were identified. Data on study design and animal model use were collected. Citations at 60 months were additionally examined as a surrogate measure of research impact in a prespecified subset of studies, stratified by individual and cumulative study design elements. Of 28 636 articles screened, 3396 met inclusion criteria. Randomization was reported in 21.8%, blinding in 32.7%, and sample size estimation in 2.3%. Temporal and disease-specific analyses show that the implementation of these study design elements has overall not appreciably increased over the past decade, except in preclinical stroke research, which has uniquely demonstrated significant improvements in methodological rigor. In a subset of 1681 preclinical studies, randomization, blinding, sample size estimation, and inclusion of both sexes were not associated with increased citations at 60 months. CONCLUSIONS: Methodological shortcomings are prevalent in preclinical cardiovascular research, have not substantially improved over the past 10 years, and may be overlooked when basing subsequent studies. Resultant risks of bias and threats to study validity have the potential to hinder progress in cardiovascular medicine as preclinical research often precedes and informs clinical trials. Stroke research quality has uniquely improved in recent years, warranting a closer examination for interventions to model in other cardiovascular fields.

Photoplethysmography using a smartphone application for assessment of ulnar artery patency: a randomized clinical trial.

BACKGROUND: Radial artery access is commonly performed for coronary angiography and invasive hemodynamic monitoring. Despite limitations in diagnostic accuracy, the modified Allen test (manual occlusion of radial and ulnar arteries followed by release of the latter and assessment of palmar blush) is used routinely to evaluate the collateral circulation to the hand and, therefore, to determine patient eligibility for radial artery access. We sought to evaluate whether a smartphone application may provide a superior alternative to the modified Allen test. METHODS: We compared the modified Allen test with a smartphone heart rate-monitoring application (photoplethysmography readings detected using a smartphone camera lens placed on the patient's index finger) in patients undergoing a planned cardiac catheterization. Test order was randomly assigned in a 1:1 fashion. All patients then underwent conventional plethysmography of the index finger, followed by Doppler ultrasonography of the radial and ulnar arteries (the diagnostic standard). The primary outcome was diagnostic accuracy of the heart rate-monitoring application. RESULTS: Among 438 patients who were included in the study, we found that the heart rate-monitoring application had a superior diagnostic accuracy compared with the modified Allen test (91.8% v. 81.7%, p = 0.002), attributable to its greater specificity (93.0% v. 82.8%, p = 0.001). We also found that this application had greater diagnostic accuracy for assessment of radial or ulnar artery patency in the ipsilateral and contralateral wrist (94.0% v. 84.0%, p < 0.001). INTERPRETATION: A smartphone application used at the bedside was diagnostically superior to traditional physical examination for confirming ulnar patency before radial artery access. This study highlights the potential for smartphone-based diagnostics to aid in clinical decision-making at the patient's bedside. Trial registration: Clinicaltrials.gov, no. NCT02519491.

Association between plasminogen activator inhibitor-1 and cardiovascular events: a systematic review and meta-analysis.

BACKGROUND: Small studies have implicated plasminogen activator inhibitor-1 (PAI-1) as a predictor of cardiovascular events; however, these findings have been inconsistent.We sought out to examine the potential role of PAI-1 as a marker for major adverse cardiovascular events (MACE). METHODS: We systematically reviewed all indexed studies examining the association between PAI-1 and MACE (defined as death, myocardial infarction, or cerebrovascular accident) or restenosis. EMBASE, Web of Science, Medline, and the Cochrane Library were searched through October 2016 to identify relevant studies, supplemented by letters to authors and review of citations. Studies reporting the results of PAI-1 antigen and/or activity levels in association with MACE in human subjects were included. RESULTS: Of 5961 articles screened, we identified 38 articles published between 1991 to 2016 that reported PAI-1 levels in 11,557 patients. In studies that examined PAI-1 antigen and activity levels, 15.1% and 29.6% of patients experienced MACE, respectively. Patients with MACE had higher PAI-1 antigen levels with a mean difference of 6.11 ng/mL (95% CI, 3.27-8.96). This finding was similar among patients with and without known coronary artery disease. Comparatively, studies that stratified by PAI-1 activity levels were not associated with MACE. In contrast, studies of coronary restenosis suggest PAI-1 antigen and activity levels are negatively associated with MACE. CONCLUSIONS: Elevated plasma PAI-1 antigen levels are associated with MACE. Definitive studies are needed to ascertain if PAI-1 acts simply as a marker of risk or if it is indeed a bona fide therapeutic target.

Evaluation of Cobalt and Chromium Levels Following Implantation of Cobalt Chromium Coronary Stents: A Pilot Study.

BACKGROUND: Large increases in myocardial trace elements may adversely affect metabolism and become detrimental to cardiac function. Percutaneous coronary intervention (PCI) allows for the revascularisation of obstructive coronary artery disease using drug-eluting stents. These stents are comprised of a metallic stent backbone covered in an engineered polymer which delivers a drug over a prescribed period to the vessel wall. Given the potential implications of trace metal accumulation within the myocardium, our goal is to determine if metallic coronary stents are able to cause detectable elevations in serum cobalt and/or chromium levels. METHODS: This study was a single centre, observational, pilot study with 20 patients who underwent planned PCI with implantation of a cobalt chromium drug eluting stent. Serum blood samples were drawn at baseline prior to PCI, 4hours post-stent deployment and at the time of routine follow-up after PCI. All blood samples were analysed for cobalt and chromium concentrations. The primary outcome of this study was the difference in serum cobalt and chromium levels at routine clinical follow-up. RESULTS: The mean follow up was 64.1±17.3 days. There was no difference in serum cobalt levels when comparing baseline and routine clinical follow up (3.32±2.14nmol/L vs. 3.14±1.00nmol/L, p=0.99) nor in chromium levels (4.24±2.31nmol/L vs. 2.82±1.22 nmol/L, p=0.11). There was also no difference between baseline and 4hours post-PCI serum concentrations. CONCLUSIONS: Percutaneous coronary intervention with cobalt chromium coronary stents does not appear to cause an elevation in these trace element serum concentrations.

Cost-effectiveness of population screening for aortic stenosis.

BACKGROUND AND AIMS: Aortic stenosis (AS) is a progressive disease predominantly affecting elderly patients that carries significant morbidity and mortality without aortic valve replacement, the only proven treatment. Our objective was to determine the cost-effectiveness of AS screening using transthoracic echocardiography (TTE) in a geriatric population from the perspective of the publicly funded healthcare system in Canada. METHODS: Markov models estimating the cost-effectiveness ratio (ICER) for AS screening with a one-time TTE were developed. The model included diagnosed and undiagnosed AS health states, hospitalizations, TAVR and post-TAVR health states. Primary analysis included screening at 70 and 80 years of age with intervention at symptom onset, with scenario analysis included for early intervention at the time of severe asymptomatic AS diagnosis. Monte Carlo simulation of 5000 replications was completed with a lifetime horizon and 1.5% discount for costs and outcomes. RESULTS: Screening for AS at the age of 70 years was associated with an ICER of $156,722 and screening at 80 years of age was associated with an ICER of $28,005, suggesting that screening at 80 years of age is cost-effective when willingness-to-pay per QALY is $50,000. Scenario analysis with early intervention was not cost-effective with an ICER of $142,157 at 70 years, and $124,651 at 80 years. CONCLUSION: Screening for AS at 80 years of age with a one-time TTE, in a Canadian population, improves quality of life and is cost-effective in a publicly funded healthcare system providing TAVR is reserved for symptomatic patients.

Sex-Related Disparities in Cardiovascular Outcomes Among Older Adults With Late-Onset Hypertension.

BACKGROUND: It is unclear whether sex-based differences in cardiovascular outcomes exist in late-onset hypertension. METHODS: This is a population-based cohort study in Ontario, Canada of 266 273 adults, aged ≥66 years with newly diagnosed hypertension. We determined the incidence of the primary composite cardiovascular outcome (myocardial infarction, stroke, and congestive heart failure), all-cause mortality, and cardiovascular death by sex using Cox proportional hazard models adjusted for demographic factors and comorbidities. RESULTS: The mean age of the total cohort was 74 years, and 135 531 (51%) were female. Over a median follow-up of 6.6 (4.7-9.0) years, females experienced a lower crude incidence rate (per 1000 person-years) than males for the primary composite cardiovascular outcome (287.3 versus 311.7), death (238.4 versus 251.4), and cardiovascular death (395.7 versus 439.6), P<0.001. The risk of primary composite cardiovascular outcome was lower among females (adjusted hazard ratio, 0.75 [95% CI, 0.73-0.76]; P<0.001) than in males. This was consistent after adjusting for the competing risk of all-cause death with a subdistributional hazard ratio, 0.88 ([95% CI, 0.86-0.91]; P<0.001). CONCLUSIONS: Females had a lower risk of cardiovascular outcomes compared with males within a population characterized by advanced age and new hypertension. Our results highlight that the severity of outcomes is influenced by sex in relation to the age at which hypertension is diagnosed. Further studies are required to identify sex-specific variations in the diagnosis and management of late-onset hypertension due to its high incidence in this group.

Efficacy of Milrinone and Dobutamine in Cardiogenic Shock: An Updated Systematic Review and Meta-Analysis.

OBJECTIVES: Inotropic support is commonly used in patients with cardiogenic shock (CS). High-quality data guiding the use of dobutamine or milrinone among this patient population is limited. We compared the efficacy and safety of these two inotropes among patients with low cardiac output states (LCOS) or CS. DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched up to February 1, 2023, using key terms and index headings related to LCOS or CS and inotropes. DATA EXTRACTION: Two independent reviewers included studies that compared dobutamine to milrinone on all-cause in-hospital mortality, length of ICU stay, length of hospital stay, and significant arrhythmias in hospitalized patients. DATA SYNTHESIS: A total of eleven studies with 21,084 patients were included in the meta-analysis. Only two randomized controlled trials were identified. The primary outcome, all-cause mortality, favored milrinone in observational studies only (odds ratio [OR] 1.19 (95% CI, 1.02-1.39; p = 0.02). In-hospital length of stay (LOS) was reduced with dobutamine in observational studies only (mean difference -1.85 d; 95% CI -3.62 to -0.09; p = 0.04). There was no difference in the prevalence of significant arrhythmias or in ICU LOS. CONCLUSIONS: Only limited data exists supporting the use of one inotropic agent over another exists. Dobutamine may be associated with a shorter hospital LOS; however, there is also a potential for increased all-cause mortality. Larger randomized studies sufficiently powered to detect a difference in these outcomes are required to confirm these findings.

Evaluation of a Rabbit Model of Vascular Stent Healing: Application of Optical Coherence Tomography.

Percutaneous coronary intervention (PCI) is a management strategy for symptomatic obstructive coronary artery disease (CAD). Despite advancements, in-stent restenosis (ISR) still imparts a 1-2% annual rate of repeat revascularization-a focus of ongoing translational research. Optical coherence tomography (OCT) provides high resolution virtual histology of stents. Our study evaluates the use of OCT for virtual histological assessment of stent healing in a rabbit aorta model, enabling complete assessment of intraluminal healing throughout the stent. ISR varies based on intra-stent location, stent length, and stent type in a rabbit model-important considerations for translational experimental design. Atherosclerosis leads to more prominent ISR proliferation independent of stent-related factors. The rabbit stent model mirrors clinical observations, while OCT-based virtual histology demonstrates utility for pre-clinical stent assessment. Pre-clinical models should incorporate clinical and stent factors as feasible to maximize translation to clinical practice.

Dipyridamole and vascular healing following stent implantation.

Introduction: Patients undergoing coronary stent implantation incur a 2% annual rate of adverse events, largely driven by in-stent restenosis (ISR) due to neointimal (NI) tissue proliferation, a process in which smooth muscle cell (SMC) biology may play a central role. Dipyridamole (DP) is an approved therapeutic agent with data supporting improved vascular patency rates. Pre-clinical data supports that DP may enact its vasculoprotective effects via adenosine receptor-A2B (ADOR-A2B). We sought to evaluate the efficacy of DP to mitigate ISR in a pre-clinical rabbit stent model. Methods & Results: 24 New Zealand White Rabbits were divided into two cohorts-non-atherosclerosis and atherosclerosis (n = 12/cohort, 6 male and 6 female). Following stent implantation, rabbits were randomized 1:1 to control or oral dipyridamole therapy for 6 weeks followed by optical coherence tomography (OCT) and histology assessment of NI burden and stent strut healing. Compared to control, DP demonstrated a 16.6% relative reduction in NI volume (14.7 ± 0.8% vs. 12.5 ± 0.4%, p = 0.03) and a 36.2% relative increase in optimally healed stent struts (37.8 ± 2.8% vs. 54.6 ± 2.5%, p < 0.0001). Atherosclerosis demonstrated attenuated effect with no difference in NI burden (15.2 ± 1.0% vs. 16.9 ± 0.8%, p = 0.22) and only a 14.2% relative increase in strut healing (68.3 ± 4.1% vs. 78.7 ± 2.5%, p = 0.02). DP treated rabbits had a 44.6% (p = 0.045) relative reduction in NI SMC content. In vitro assessment of DP and coronary artery SMCs yielded dose-dependent reduction in SMC migration and proliferation. Selective small molecule antagonism of ADOR-A2B abrogated the effects of DP on SMC proliferation. DP modulated SMC phenotypic switching with ADOR-A2B siRNA knockdown supporting its role in the observed effects. Conclusion: Dipyridamole reduces NI proliferation and improves stent healing in a preclinical model of stent implantation with conventional antiplatelets. Atherosclerosis attenuates the observed effect. Clinical trials of DP as an adjunctive agent may be warranted to evaluate for clinical efficacy in stent outcomes.

Arrhythmic Events and Mortality in Patients With Cardiogenic Shock on Inotropic Support: Results of the DOREMI Randomized Trial.

BACKGROUND: Inotropic support is widely used in the management of cardiogenic shock (CS). Existing data on the incidence and significance of arrhythmic events in patients with CS on inotropic support is at high risk of bias. METHODS: The Dobutamine Compared to Milrinone (DOREMI) trial randomized patients to receive dobutamine or milrinone in a double-blind fashion. Patients with and without arrhythmic events (defined as arrhythmias requiring intervention or sustained ventricular arrhythmias) were compared to identify factors associated with their occurrence, and to examine their association with in-hospital mortality and secondary outcomes. RESULTS: Ninety-two patients (47.9%) had arrhythmic events, occurring equally with dobutamine and milrinone (P = 0.563). The need for vasopressor support at initiation of the inotrope and a history of atrial fibrillation were positively associated with arrhythmic events, whereas predominant right ventricular dysfunction, previous myocardial infarction, and increasing left ventricular ejection fraction were negatively associated with them. Supraventricular arrhythmic events were not associated with mortality (relative risk [RR], 0.97; 95% confidence interval [CI], 0.68-1.40; P = 0.879) but were positively associated with resuscitated cardiac arrests and hospital length of stay. Ventricular arrhythmic events were positively associated with mortality (RR, 1.66; 95% CI, 1.13-2.43; P = 0.026) and resuscitated cardiac arrests. Arrhythmic events were most often treated with amiodarone (97%) and electrical cardioversion (27%), which were not associated with mortality. CONCLUSIONS: Clinically relevant arrhythmic events occur in approximately one-half of patients with CS treated with dobutamine or milrinone and are associated with adverse clinical outcomes. Five factors may help to identify patients most at risk of arrhythmic events.

Diagnostic accuracy of point-of-care ultrasound with artificial intelligence-assisted assessment of left ventricular ejection fraction.

Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice (n = 208) and 0.845 in the experienced (n = 216) cohorts. There was a significant bias of 0.73% towards TTE (p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings.

Milrinone vs Dobutamine for the Management of Cardiogenic Shock: Implications of Renal Function and Injury.

Background: Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction. Objectives: This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function. Methods: In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Results: Baseline eGFR <60 ml/min/1.73 m2 and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m2 did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome (P interaction = 0.02) and death (P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI. Conclusions: In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

Stress Perfusion Cardiac Magnetic Resonance Imaging With a 3.0-Tesla Scanner for Myocardial Viability in a Patient With a Conditional Pacemaker.

Cardiac magnetic resonance (CMR) imaging provides images with high spatial and temporal resolution, with high diagnostic and prognostic performance. An abundance of data indicate the safety and efficacy of noncardiac magnetic resonance imaging at both 1.5 Tesla (T) and 3T in patients with cardiac implantable electronic devices (CIEDs). Safety and efficacy have also been evaluated for stress perfusion (SP)-CMR for pateints with CIEDs, using 1.5T scanners, but no previous reports have been made of SP-CMR using 3T scanners. Herein, we report a case of a patient with a CIED who successfully and safely underwent SP-CMR imaging using a 3T scanner.

L'imagerie par résonance magnétique cardiaque (IRMC) procure des images à haute résolution spatiale et temporelle en plus d'offrir une capacité diagnostique et pronostique élevée, mais une multitude de données mettent en lumière l'innocuité et l'efficacité de l'imagerie non cardiaque réalisée au moyen d'appareils d'IRM produisant un champ magnétique de 1,5 ou de 3 teslas (T) chez des patients porteurs d'un dispositif cardiaque électronique implantable (DCEI). L'innocuité et l'efficacité de l'évaluation de la perfusion à l'effort (EPE) par IRMC ont aussi été évaluées chez des patients porteurs d'un DCEI au moyen d'appareils produisant un champ magnétique de 1,5 T, mais pas au moyen d'appareils produisant un champ magnétique de 3 T. Nous rapportons ici le cas d'un patient porteur d'un DCEI ayant subi avec succès et en toute sécurité une EPE par IRMC réalisée au moyen d'un appareil produisant un champ magnétique de 3 T.