Arun Krishnamoorthy

Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure

Background In an early analysis of this trial, use of a magnetically levitated centrifugal continuous‐flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical‐bearing axial continuous‐flow pump, at 6 months in patients with advanced heart failure. Methods In a randomized noninferiority and superiority trial, we compared the centrifugal‐flow pump with the axial‐flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal‐flow pump group minus axial‐flow pump group) was ‐10 percentage points. Results Of 366 patients, 190 were assigned to the centrifugal‐flow pump group and 176 to the axial‐flow pump group. In the intention‐to‐treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal‐flow pump group, as compared with 106 (60.2%) in the axial‐flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal‐flow pump group than in the axial‐flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal‐flow pump group than in the axial‐flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). Conclusions In patients with advanced heart failure, a fully magnetically levitated centrifugal‐flow pump was superior to a mechanical‐bearing axial‐flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.)

Transient and persistent worsening renal function during hospitalization for acute heart failure

BACKGROUND Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF. METHODS We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (< 0.3 mg/dL) or persistent WRF (≥ 0.3 mg/dL). We examined unadjusted rates and adjusted associations between 90-day outcomes and WRF status. RESULTS Among 27,309 patients, 18,568 (68.0%) had no WRF, 3,205 (11.7%) had transient WRF, and 5,536 (20.3%) had persistent WRF. Patients with WRF had higher observed rates of 90-day postdischarge all-cause readmission and 90-day postadmission mortality (P < .001). After multivariable adjustment, transient WRF (hazard ratio [HR] 1.19, 99% CI 1.05-1.35) and persistent WRF (HR 1.73, 99% CI 1.57-1.91) were associated with higher risks of 90-day postadmission mortality (P < .001 for both). Compared with transient WRF, persistent WRF was associated with a higher risk of 90-day postadmission mortality (HR 1.46, 99% CI 1.28-1.66, P < .001). CONCLUSIONS Transient and persistent WRF during hospitalization for acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes.

The impact of a failing right heart in patients supported by intra-aortic balloon counterpulsation.

Background: Intra-aortic balloon pumps (IABPs) provide primarily left ventricular support, yet few data detail the efficacy of this temporary mechanical circulatory support device in patients with concomitant right ventricular failure. We compared the efficacy of IABPs in cardiogenic shock patients with isolated left ventricular versus biventricular failure. Methods: IABP-treated cardiogenic shock patients were identified from our center between 2006 and 2012, with patients stratified by either isolated left ventricular failure or biventricular failure. We compared baseline characteristics and 72-hour and 30-day outcomes between groups. Outcomes of interest included escalation of mechanical circulatory support, a clinical definition of IABP failure, and death. Results: Among 107 patients, 60 patients (56%) had isolated left ventricular failure compared with 47 patients (44%) having biventricular failure. Patients with isolated left ventricular failure were older and more likely to have coronary artery disease (p<0.05, both). Patients with biventricular failure more often required escalation of mechanical circulatory support at both 72 hours (21% vs. 2%, p<0.001) and 30 days (36% vs. 30%). However, there was no significant difference between groups for failure of IABP therapy at 72 hours (p=0.27) or at 30 days (p=0.62) and death at 30 days (p=0.98). In adjusted analysis, there was no significant difference between groups with regard to risk for a clinical definition of IABP failure at 30 days (odds ratio=0.85, 95% confidence interval (0.27, 2.69)). Conclusions: IABP-treated cardiogenic shock patients with biventricular failure more often required early escalation of mechanical circulatory support. However, there were no significant differences by type of ventricular failure with regard to 30-day outcomes.

A crisis of the heart: an acute reversible cardiomyopathy bridged to recovery in a patient with Addison's disease.

Primary adrenal insufficiency or Addisons disease is a rare disorder often difficult to diagnose on presentation by the nature of its associated nonspecific symptoms, such as nausea or weakness. Cardiovascular complications of the condition are usually limited to hypovolemic hypotension; however, we highlight here a rare, dramatic case of a fulminant adrenal crisis in a young man primarily marked by acute biventricular systolic failure and cardiogenic shock. The patient was successfully treated with corticosteroid replacement and bridged with temporary mechanical circulatory support to eventual complete the recovery of native myocardial function.

The periprocedural management of novel oral anticoagulants in patients with nonvalvular atrial fibrillation: rationale and a summary of the available evidence from phase 3 clinical trials.

The novel oral anticoagulants (NOACs) have rapidly emerged as an alternative therapy to warfarin. Several recent phase 3 randomized control trials have demonstrated the efficacy and safety of the NOACs in the treatment for patients with nonvalvular atrial fibrillation. As the NOACs are incorporated in clinical practice, questions have begun to arise concerning their optimal use in commonly encountered situations. In this review, we provide a summary of the available evidence from the phase 3 randomized control trials specifically with regard to 1 such scenario, the periprocedural management of NOACs, with a goal of providing guidance for practicing clinicians.

Accuracy of Medical Claims for Identifying Cardiovascular and Bleeding Events After Myocardial Infarction : A Secondary Analysis of the TRANSLATE-ACS Study

Importance Pragmatic clinical trial designs have proposed the use of medical claims data to ascertain clinical events; however, the accuracy of billed diagnoses in identifying potential events is unclear. Objectives To compare the 1-year cumulative incidences of events when events were identified by medical claims vs by physician adjudication and to assess the accuracy of bill-identified events using physician adjudication as the criterion standard. Design, Setting, and Participants This post hoc analysis of a clinical trial assessed the medical claims forms and records for all rehospitalizations at 233 US hospitals within 1 year of the index acute myocardial infarction (MI) of 12 365 patients enrolled in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study between April 1, 2010, and October 31, 2012. Fourteen patients (0.1%) died during the index hospitalization and were excluded from analysis. Recurrent MI, stroke, and bleeding events were identified per the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedural codes in medical bills. These events were independently adjudicated by study physicians through medical record reviews using the prespecified criteria of recurrent MI and stroke and the bleeding definition by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) scale. Medical claims were reported on a Uniform Bill-04 claims form; claims were collected from all hospitals visited by patients enrolled in TRANSLATE-ACS. Agreement between medical claims–identified events and physician-adjudicated events over the 12 months after discharge was assessed with the &kgr; statistic. Data were analyzed from January 30, 2015, to March 2, 2017. Main Outcomes and Measures Event rates within 1 year after MI. Results Among 12 365 patients with acute MI, 8890 (71.9%) were men and mean (SD) age was 60 (11.6) years. The cumulative 1-year incidence of events identified by medical claims was 4.3% for MI, 0.9% for stroke, and 5.0% for bleeding. Incidence rates based on physician adjudication were 4.7% for MI, 0.9% for stroke, and 5.4% for bleeding. Agreement between medical claims–identified and physician-adjudicated events was modest, with a &kgr; of 0.76 (95% CI, 0.73 to 0.79) for MI and 0.55 (95% CI, 0.41 to 0.68) for stroke events. In contrast, agreement between medical claims–identified and physician-adjudicated bleeding events was poor, with a &kgr; of 0.24 (95% CI, 0.19 to 0.30) for any hospitalized bleeding event and 0.15 (95% CI, 0.11 to 0.20) for moderate or severe bleeding on the GUSTO scale. Conclusions and Relevance Event rates at 1 year after MI were lower for MI, stroke, and bleeding when medical claims were used to identify events than when adjudicated by physicians. Medical claims diagnoses were only modestly accurate in identifying MI and stroke admissions but had limited accuracy for bleeding events. An alternative approach may be needed to ensure good safety surveillance in cardiovascular studies. Trial Registration clinicaltrials.gov Identifier: NCT01088503

How Reliable are Patient‐Reported Rehospitalizations? Implications for the Design of Future Practical Clinical Studies

Background Longitudinal clinical investigations often rely on patient reports to screen for postdischarge adverse outcomes events, yet few studies have examined the accuracy of such patient reports. Methods and Results Patients with acute myocardial infarction (MI) in the TRANSLATE‐ACS study were asked during structured interviews at 6 weeks, 6 months, and 12 months postdischarge to report any rehospitalizations. The accuracy of patient‐reported rehospitalizations within 1 year of postdischarge was determined using claims‐based medical bill validation as the reference standard. The cumulative incidence of rehospitalizations was compared when identified by patient report versus medical bills. Patients were categorized by the accuracy in reporting events (accurate, under‐, or over‐ reporters) and characteristics were compared between groups. Among 10 643 MI patients, 4565 (43%) reported 7734 rehospitalizations. The sensitivity and positive predictive value of patient‐reported rehospitalizations were low at 67% and 59%, respectively. A higher cumulative incidence of rehospitalization was observed when identified by patient report versus medical bills (43% vs 37%; P<0.001). Overall, 18% of patients over‐reported and 10% under‐reported the number of hospitalizations. Compared with accurate reporters, under‐reporters were more likely to be older, female, African American, unemployed, or a non‐high‐school graduate, and had greater prevalence of clinical comorbidities such as diabetes and past cardiovascular disease. Conclusions The accuracy of patient‐reported rehospitalizations was low with patients both under‐ and over‐reporting events. Longitudinal clinical research studies need additional mechanisms beyond patient report to accurately identify rehospitalization events. Clinical Trial Registration URL: https://clinicaltrials.gov. Unique identifier: NCT01088503.

Identifying Barriers and Practical Solutions to Conducting Site-Based Research in North America Exploring Acute Heart Failure Trials As a Case Study

Although the prognosis of ambulatory heart failure (HF) has improved dramatically there have been few advances in the management of acute HF (AHF). Despite regional differences in patient characteristics, background therapy, and event rates, AHF clinical trial enrollment has transitioned from North America and Western Europe to Eastern Europe, South America, and Asia-Pacific where regulatory burden and cost of conducting research may be less prohibitive. It is unclear if the results of clinical trials conducted outside of North America are generalizable to US patient populations. This article uses AHF as a paradigm and identifies barriers and practical solutions to successfully conducting site-based research in North America.

Assessment of cardiac allograft systolic function by global longitudinal strain: From donor to recipient

Cardiac allografts are routinely evaluated by left ventricular ejection fraction (LVEF) before and after transplantation. However, myocardial deformation analyses with LV global longitudinal strain (GLS) are more sensitive for detecting impaired LV myocardial systolic performance compared with LVEF.

A Bridge to Nowhere? Benefits and Risks for Periprocedural Anticoagulation in Atrial Fibrillation.

In patients with atrial fibrillation (AF), oral anticoagulation is used to prevent stroke and systemic embolism. In a common clinical scenario, AF patients frequently undergo invasive procedures requiring temporary interruption of oral anticoagulation, thereby potentially exposing such patients to increased risk of thromboembolism. Bridging anticoagulation has been used clinically to mitigate this perceived thromboembolic risk, though this practice may also increase risk of periprocedural bleeding. High-quality data has not previously existed to inform decision-making in this clinical situation of bridging anticoagulation. We discuss recent results from the BRIDGE trial and secondary analyses from recent phase 3 randomized clinical trials of direct-acting oral anticoagulant (DOAC) use in non-valvular AF, that inform periprocedural anticoagulation with bridging strategies in AF patients. Updated data from these current trials favor against a strategy of bridging anticoagulation for elective procedures in the majority of AF patients, low or moderate in thromboembolic risk. Bridging anticoagulation is associated with an increased risk of bleeding and no decreased risk of thromboembolism.