Lerman, Amir

Abstract Background Cancer patients have a higher risk of thromboembolic events but it is not well known if these patients also have a higher risk of death, myocardial infarction (MI) or repeat revascularization after percutaneous coronary intervention (PCI) is unknown. Methods Cancer patients who underwent first-time single vessel PCI from January 1, 2003, through December 31, 2013 were identified by cross-matching of institutional cancer and PCI registries. These cancer patients were matched 4:1 to non-cancer patients, likewise undergoing first-time single vessel PCI in the time period. The combined primary endpoint was death, MI and revascularization at 5 year follow-up. Secondary endpoints were death and MI combined and the individual components of the primary endpoint. Both time dependent and non-time-dependent analyses were conducted. Results A total of 712 cancer patients were identified and matched to 2,848 non-cancer patients (one third women in either group). Bare-metal stents were used in one third of patients in both groups. The combined primary study endpoint was significantly more frequently encountered in the cancer than in the non-cancer group in both time-dependent (Figure 1) and non-time dependent analyses (5-year event rate 48.6% vs. 31.2%, p<0.001). This was driven by a higher 5-year event rate of death (39.0% vs. 20.1%) and MI (14.8% vs 4.86%) in the cancer group. The 5-year rate of revascularization did not differ significantly between the two groups (10.5% vs 10.3%). Figure 1. MI + revascularization-survival Conclusion Cancer patients have a two times higher rate of death and a three times higher rate of MI over the first 5 years after PCI. Future studies will need to define the etiology and factors accounting for this higher event rate in cancer patients, especially of these patients are predisposed to stent thrombosis and need longer term dual antiplatelet therapy.

Abstract Background: Proteasome inhibitors and immunomodulatory drugs are currently an integral part of the management of multiple myeloma. Pre-clinical and clinical studies suggest that bortezomib, the first approved proteasome inhibitor for the management of multiple myeloma, may be associated with an increased risk of cardiac events such as heart failure (HF), acute myocardial infarction (MI), and arrhythmia. The goal of this study was to evaluate the rate of adverse cardiac events in patients treated with bortezomib compared to lenalidomide. Methods: This retrospective, propensity-matched study using a large, national administrative claims database included multiple myeloma patients who initiated bortezomib and a comparison group (matched on age, sex, year of drug initiation, baseline HF, hyperlipidemia, hypertension, history of MI, arrhythmia and Charlson comorbidity index) who initiated lenalidomide between January 2008 and December 2014. Those who received both bortezomib and lenalidomide were excluded from the analysis. The primary endpoints were time to hospitalization for HF, acute MI and arrhythmia. Rates of hospitalizations were computed per 100 patient years (PY). Cox proportional hazard models were used to obtain hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 1,128 patients (564 bortezomib users and 564 lenalidomide users, mean age of 69, 47% female, and average follow-up time of 438 days) were included in the analysis. The rate of hospitalization for HF, acute MI, and arrhythmia was 5.76/100 PY, 2.57/100 PY, and 3.10/100 PY respectively among bortezomib users and 2.45/100 PY, 1.47/100 PY, and 2.85/100 PY respectively among lenalidomide users. In the propensity score matched models, the risk of hospitalization for acute MI and arrhythmia with bortezomib was similar to lenalidomide (HR 1.60 [95% CI 0.73-3.49] and HR 1.01 [95% CI 0.54-1.90] respectively). The risk of hospitalization for HF with bortezomib use was significantly higher compared to lenalidomide (HR 2.10 [95% CI 1.18-3.74], Figure 1). Further stratification of the patient population by baseline HF status showed that those with baseline HF (n=212) were significantly more likely to be hospitalized for HF following treatment with bortezomib compared to lenalidomide. The rate of hospitalization for HF in the population with baseline HF was 24.12/100 PY among bortezomib users and 8.77/100 PY among lenalidomide users (HR 2.24 [95% CI 1.04-4.83]). Those without baseline HF (n=916) had similar rates of hospitalization for HF when treated with bortezomib and lenalidomide (2.83/100 PY and 1.29/100 PY respectively, HR 2.05 [95% CI 0.86-4.91]). Conclusion: The current study shows that bortezomib use in patients treated for multiple myeloma is associated with an increased risk of hospitalization for heart failure, but not acute MI or arrhythmia. Those with HF prior to initiating therapy with bortezomib had a significantly increased risk of hospitalization for HF when compared to those treated with lenalidomide. There was no significant difference in the rate of hospitalization for HF in those without a baseline diagnosis of HF. Collectively, these data have important implications for the management of patients with multiple myeloma, especially those with a history of HF at the time of therapy initiation. Figure 1. Kaplan Meier plot for HF hospitalizations. Figure 1. Kaplan Meier plot for HF hospitalizations. Disclosures No relevant conflicts of interest to declare.

Background: We aim to study the incidence of major complications related to procedure defined as in-hospital death, myocardial infarction, stroke, pericardial effusion or tamponade, percutaneous coronary intervention due to iatrogenic coronary dissection, or unplanned bypass surgery within 72 hours after diagnostic left heart catheterization (LHC; primary end point). Furthermore, all causes of in-hospital death after LHC were adjudicated and reported (secondary end point). Methods and Results: Diagnostic LHC procedures (aortic angiography; coronary, including graft, angiography; and left ventricular angiography) from January 1, 2002, through December 31, 2013, were identified using the clinical scheduling system at Mayo Clinic, Rochester, and complications were identified through electronic records. International Classification of Diseases, Ninth Revision billing codes were used. Registration was queried to identify all-cause mortality. All events were reviewed and adjudicated. There were 43 786 diagnostic LHC procedures; 97.3% were coronary angiograms. The mean age of patients was 64.5 years (13.6), and the majority were male (61.5%). Primary end point was seen in 36 (0.082%) procedures or 8.2 of 10 000 LHCs. Combined right sided procedures with LHC did not increase the risk of major complications. Cardiogenic and septic shock, cardiac arrhythmia, and postsurgical complication were the most common causes of in-hospital death after LHC. Conclusions: The overall rates of major complications related to diagnostic cardiac catheterization procedures are extremely rare. The majority of the deaths occurring post-diagnostic LHC procedures were secondary to acute illness rather than directly related to diagnostic procedure.

Background Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles ( EV s), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that EV s released by senescent nephron cells can be identified in urine of patients with hypertension. Methods and Results We recruited patients with essential hypertension ( EH ) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine‐level measurements. EV s isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin‐2 (distal tubules). Overall percentage of urinary p16+ EV s was elevated in EH and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16 + /urate transporter 1 + were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16 + /prominin‐2 + levels were elevated only in EH versus healthy volunteers and p16 + /uromodulin + in renovascular hypertension versus EH . Conclusions Levels of p16 + EV s are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In EH , EV s originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary EV s levels may be useful to identify intrarenal sites of cellular senescence.

Background: Reducing door-to-balloon time may not reduce mortality, but reducing the time from symptom onset to first medical contact (FMC) may alone improve patient outcomes. The purpose of this study was to focus on analyzing sex differences in FMC call delay and its trend over the decades in patients with suspected acute coronary syndrome (ACS). Methods: Large private telemedicine data in patients with suspected ACS were used to investigate time delay in contacting a telemedicine call center. We identified 24,592 calls to a primary call center of patients with anginal symptoms and first electrocardiogram (ECG), using mobile 12-lead ECG devices. For the purpose of the current analysis, we included the first call of 14,420 patients for whom demographic, clinical ECG data were available. Results: First mobile ECG changes included suspected S-T Segment (ST) elevation in 2,220 (16%) cases, ST depression in 3,143 (22%) cases, or both in 685 (5%) patients. There were 6,721 (47%) calls to the center within less than 1 h of symptom onset. Chest pain, dyspnea, heart rate, male sex, absence of diabetes mellitus, early time period of the study, and ischemic ST segment changes on the first ECG were all independently associated with the increased likelihood of contacting the center within less than 1 h of symptom onset to FMC ( p < 0.01 for all). Conclusions: Both chest pain and ischemic ECG changes were sex dependent for early medical contact, as such factors were significant among men ( p = 0.001 and p = 0.024, respectively), but not among women ( p = 0.024). The later time period of the study was associated with a shorter time delay among women more than that of men ( p = 0.014). Women with prehospital chest pain or ischemic ST segment changes tend to seek medical help later than men. Temporal trends show attenuation of this sex disparity, with more women presenting earlier in the last decade.

Background Women with non‐obstructive coronary artery disease have increased cardiovascular morbidity. The role of risk factors in this population has yet to be established. We aimed to study the predictive effect of triglycerides and the triglyceride/high‐density lipoprotein ratio on major adverse cardiovascular events (MACE) in patients with non‐obstructive coronary artery disease, and to explore the role of lipid lowering therapy in modifying this risk. Methods and Results This is a prospective cohort study enrolling patients with anginal symptoms referred to the cardiac catheterization laboratory for suspected ischemia, who were subsequently diagnosed with non‐obstructive coronary artery disease, defined as no stenosis >20% on angiography. All patients had baseline laboratory testing and were followed for 7.8±4.3 years for the development of major adverse cardiovascular events. We performed Cox proportional hazard testing to determine the effect of triglycerides on risk of major adverse cardiovascular events among men and women by baseline statin use. A total of 462 patients were included. Median age was 53 (Q1, Q3: 45, 62) years. In a Cox proportional hazard model stratified by statin use adjusting for confounders, among those not on baseline statins, triglycerides were independently predictive of major adverse cardiovascular events in women (per 50 mg/dL risk ratio: hazard ratio 1.25 [95% CI : 1.06, 1.47]; P =0.01). This was not true among men. The interaction between triglycerides and sex, and triglycerides and statin was statistically significant. Conclusions Triglyceride levels may play a key role in predicting cardiovascular‐specific risk in women, and statin use may be protective. Further investigation is necessary to better delineate the role of statin use in preventing cardiovascular risk.