Ventricular Arrhythmia in Cancer Patients: Mechanisms, Treatment Strategies and Future Avenues.

Cardiovascular disease and cancer are the leading causes of morbidity and mortality in the US. Despite the significant progress made in cancer treatment leading to improved prognosis and survival, ventricular arrhythmias (VA) remain a known cardiovascular complication either exacerbated or induced by the direct and indirect effects of both traditional and novel cancer treatments. Although interruption of cancer treatment because of VA is rarely required, knowledge surrounding this issue is essential for optimising the overall care of patients with cancer. The mechanisms of cancer-therapeutic-induced VA are poorly understood. This review will discuss the ventricular conduction (QRS) and repolarisation abnormalities (QTc prolongation), and VAs associated with cancer therapies, as well as existing strategies for the identification, prevention and management of cancer-treatment-induced VAs.

Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm?

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i.

Sex Differences in Outcomes of Percutaneous Pulmonary Artery Thrombectomy in Patients With Pulmonary Embolism.

BACKGROUND: The sex differences in use, safety outcomes, and health-care resource use of patients with pulmonary embolism (PE) undergoing percutaneous pulmonary artery thrombectomy are not well characterized. RESEARCH QUESTION: What are the sex differences in outcomes for patients diagnosed with PE who undergo percutaneous pulmonary artery thrombectomy? STUDY DESIGN AND METHODS: This retrospective cross-sectional study used national inpatient claims data to identify patients in the United States with a discharge diagnosis of PE who underwent percutaneous thrombectomy between January 2016 and December 2018. We evaluated the demographics, comorbidities, safety outcomes (in-hospital mortality), and health-care resource use (discharge to home, length of stay, and hospital charges) of patients with PE undergoing percutaneous thrombectomy. RESULTS: Among 1,128,904 patients with a diagnosis of PE between 2016 and 2018, 5,160 patients (0.5%) underwent percutaneous pulmonary artery thrombectomy. When compared with male patients, female patients showed higher procedural bleeding (16.9% vs 11.2%; P < .05), required more blood transfusions (11.9% vs 5.7%; P < .05), and experienced more vascular complications (5.0% vs 1.5%; P < .05). Women experienced higher in-hospital mortality (16.9% vs 9.3%; adjusted OR, 1.9; 95% CI, 1.2-3.0; P = .003) when compared with men. Although length of stay and hospital charges were similar to those of men, women were less likely to be discharged home after surviving hospitalization (47.9% vs 60.3%; adjusted OR, 0.7; 95% CI, 0.50-0.99; P = .04). INTERPRETATION: In this large nationwide cohort, women with PE who underwent percutaneous thrombectomy showed higher morbidity and in-hospital mortality compared with men.

National Trends in Heart Failure Hospitalizations and Readmissions From 2010 to 2017.

Importance: Previous studies have described the secular trends of overall heart failure (HF) hospitalizations, but the literature describing the national trends of unique index hospitalizations and readmission visits for the primary management of HF is lacking. Objectives: To examine contemporary overall and sex-specific trends of unique primary HF (grouped by number of visits for the same patient in a given year) and 30-day readmission visits in a large national US administrative database from 2010 to 2017. Design, Setting, and Participants: This cohort study used data from all adult hospitalizations in the Nationwide Readmission Database from January 1, 2010, to December 31, 2017, with a primary diagnosis of HF. Data analyses were conducted from March to November 2020. Exposures: Admission for a primary diagnosis of HF at discharge. Main Outcomes and Measures: Unique and overall hospitalizations with a primary diagnosis of HF and postdischarge readmissions. Unique primary HF hospitalizations were grouped by number of visits for the same patient in a given year. Results: There were 8 273 270 primary HF hospitalizations with a single primary HF admission present in 5 092 626 unique patients, and 1 269 109 had 2 or more HF hospitalizations. The mean age was 72.1 (95% CI, 72.0-72.3) years, and 48.9% (95% CI, 48.7-49.0) were women. The primary HF hospitalization rates per 1000 US adults declined from 4.4 in 2010 to 4.1 in 2013 and then increased from 4.2 in 2014 to 4.9 in 2017. The rates per 1000 US adults for postdischarge HF readmissions (1.0 in 2010 to 0.9 in 2014 to 1.1 in 2017) and all-cause 30-day readmissions (0.8 in 2010 to 0.7 in 2014 to 0.9 in 2017) had similar trends. Conclusions and Relevance: In this analysis of a nationally representative administrative data set, for primary HF admissions, crude rates of overall and unique patient hospitalizations declined from 2010 to 2014 followed by an increase from 2014 to 2017. Additionally, readmission visits after index HF hospitalizations followed a similar trend. Future studies are needed to verify these findings to improve policies for HF management.

Clinical Outcomes of Warfarin Initiation in Advanced Chronic Kidney Disease Patients With Incident Atrial Fibrillation.

OBJECTIVES: The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis. BACKGROUND: The clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown. METHODS: In this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA-related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event-related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities. RESULTS: The mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA2DS2-VASc score was 5.7 ± 2.1. Of the overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow-up period. The hazard ratios (95% confidence intervals) for ischemic CVA, bleeding events, and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97), respectively, compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic CVA and bleeding event-related hospitalizations. CONCLUSIONS: In patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.

Cardiovascular Disease in Hospitalized Patients With a Diagnosis of Coronavirus From the Pre-COVID-19 Era in United States: National Analysis From 2016-2017.

OBJECTIVE: To analyze the cardiovascular disease (CVD) burden in hospitalized patients with a diagnosis of coronavirus from the pre-coronavirus disease 2019 era in the United States. PATIENTS AND METHODS: We identified hospitalized adults with a diagnosis of coronavirus in a large US administrative database, the National (Nationwide) Inpatient Sample, from January 1, 2016, to December 3, 2017, to study patient demographic characteristics, clinical comorbidities, and outcomes (in-hospital mortality and health care resource utilization) based on the presence or absence of CVD. RESULTS: A total of 21,300 hospitalized adults with a diagnosis of coronavirus in 2016 and 2017 from all across the United States were included in the final analysis; the mean age was 63.6 years, 11,033 (51.8%) were female, and 15,911 (74.7%) had public insurers. Among these hospitalized patients, 11,930 (56.0%) had a diagnosis of CVD. Compared with those without CVD, the patients with CVD were older (70.1 vs 55.4 years) and had higher Charlson comorbidity index scores (2.5 vs 1.6) and Elixhauser comorbidity index scores (4.3 vs 2.4) (all P<.001). After multivariable risk adjustment, patients with CVD had higher mortality than those without CVD (5.3% [632 of 11,930] vs 1.5% [140 of 9370]; adjusted odds ratio, 2.0 [95% CI, 1.2 to 3.4]; P=.008). The mean length of hospital stay (6.9 vs 6.1 days; P=.003), hospital charges ($78,377 vs $66,538; P=.002), and discharge to nursing home (24.6% [2945 of 11,930] vs 12.9% [1208 of 9370]; P<.001) were higher in those with CVD compared with the patients without CVD. CONCLUSION: Cardiovascular disease was present in a notable proportion of hospitalized patients with coronavirus in the pre-coronavirus disease 2019 era in United States and was associated with higher risk of in-hospital mortality and health care resource utilization.

Individuals with Peripheral Artery Disease (PAD) and Type 1 Diabetes Are More Likely to Undergo Limb Amputation than Those with PAD and Type 2 Diabetes.

BACKGROUND: Limited data exist comparing how type 1 diabetes mellitus (DM) and type 2 DM may have differential effects on peripheral artery disease (PAD) severity. We aimed to study the association of type of DM with the procedure utilized in hospitalizations with a diagnosis of PAD. METHODS: We used the national inpatient sample databases from 2003 to 2014 to identify hospitalizations with a diagnosis of PAD and type 1 or type 2 DM. Logistic regression was utilized to evaluate the association between type of DM and procedure utilized (amputation-overall, major, endovascular revascularization, surgical revascularization). RESULTS: We identified 14,012,860 hospitalizations with PAD diagnosis and DM, 5.6% (n = 784,720) had type 1 DM. The patients with type 1 DM were more likely to present with chronic limb-threatening ischemia (CLTI) (45.2% vs. 32.0%), ulcer (25.9% vs. 17.7%), or complicated ulcer (16.6% vs. 10.5%) (all p < 0.001) when compared to those with type 2 DM. Type 1 DM was independently and significantly associated with more amputation procedures (adjusted odds ratio = 1.12, 95% confidence interval [CI] I 1.08 to 1.16, p < 0.001). Overall, in-hospital mortality did not differ between the individuals with type 1 and type 2 DM. The overall mean (95% CI) length of stay (in days) was 6.6 (6.5 to 6.6) and was significantly higher for type 1 DM (7.8 [7.7 to 8.0]) when compared to those with type 2 DM (6.5 [6.4 to 6.6]). CONCLUSION: We observed that individuals with PAD and type 1 DM were more likely to present with CLTI and ulcer and undergo amputation when compared to those with PAD and type 2 diabetes. Further studies are needed to better understand the underlying mechanisms behind these findings and to identify novel interventions to reduce the risk of amputation in patients with type 1 DM.

Outcomes of Early Versus Delayed Transcatheter Closure of Post-Myocardial Infarction Ventricular Septal Defect.

BACKGROUND: Post myocardial infarction ventricular septal defect (VSD) is a rare, but devastating complication which carries a poor prognosis if left untreated. Optimal therapy remains unclear and surgical repair is associated with high mortality. OBJECTIVE: The aim of our study is to compare 30-day survival in patients with early versus late primary transcatheter repair of post myocardial infarction ventricular septal defect. METHODS: We performed a comprehensive search of published data through SCOPUS and identified published reports of primary transcatheter closure of post myocardial infarction VSD. We included case reports and series that reported timing of VSD closure and 30-day survival and excluded those with prior surgical repair. Early repair was defined as transcatheter closure within 14 days of diagnosis of VSD while late repair was defined as transcatheter closure after 14 days of diagnosis of VSD. RESULTS: A total 27 publications describing 193 patients were identified in the SCOPUS search. We excluded 8 publications with no reported timing of VSD repair or 30-day outcome. Of the 193 patients initially included, a total of 126 patients fulfilled all the criteria and were included in the final analysis. The overall 30-day survival rate was found to be 62.7% (79 patients). In the early repair group, only 36.2% of the patients were still alive at 30 days compared to 85.3% in the delayed repair group, P < .01. No significant difference in age, gender, presence of shock, VSD size, presence of significant residual shunt, location of VSD or infarction was observed. The early repair group was found to have a significantly larger Qp: Qs ratio as well as larger occluder size and lower rate of successful repair. CONCLUSION: Compared to the late repair group, the early transcatheter VSD repair group had a larger pre-procedure Qp:Qs and worse 30-day survival. Further studies are needed to determine the optimal timing of transcatheter repair of a post myocardial infarction VSD.

Association of history of heart failure with hospital outcomes of hyperglycemic crises: Analysis from a University hospital and national cohort.

AIMS: The impact of a history of heart failure (HF) on the outcomes of hospitalization for hyperglycemic crises (diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome) is unknown. We aimed to test the hypothesis that a history of HF has a deleterious impact on the outcomes of hospitalization for hyperglycemic crises. METHODS: We used two different datasets: National Inpatient Sample database 2003-2014 and a single University hospital cohort 2007-2017, to identify all adult hospitalizations with a primary diagnosis of hyperglycemic crises. Multivariable regression models were used to analyze the outcomes of in-hospital mortality, length of hospital stay and transfer to nursing home or similar short-term facility between HF and no-HF hospitalizations. RESULTS: Of the 1, 570,726 hyperglycemic crises related hospitalizations, a history of HF was present in 57, 520 (3.6%) hospitalizations. After multivariable risk-adjustment, HF group had a higher observed in-hospital mortality [0.4% vs. 0.2%; adjusted odds ratio (AOR) = 1.7, 95% CI 1.4 to 2.0, P < .001] and transfer to nursing home or similar short-term facility (3.9 vs. 2.8%, AOR = 1.4, 95% CI 1.3 to 1.5, P < .001) compared with no-HF group. Mean length of hospital stay [6.5 vs. 3.5 days; P < .001] was also higher for HF group than no-HF group. Data from the smaller University hospital cohort showed similar findings. CONCLUSIONS: Patients with a history of HF may be an under-recognized high-risk group among patients hospitalized for hyperglycemic crisis. Additional studies are warranted to clarify risk elements and optimize the inpatient care of individuals with hyperglycemic crises.

Relation of Obesity to Outcomes of Hospitalizations for Atrial Fibrillation.

Obesity has been linked with increased incidence of atrial fibrillation (AF), but impact of presence of obesity on outcomes of hospitalizations for AF has not been investigated. We used the National Inpatient Sample database 2010 to 2014 to identify all adult hospitalizations aged ≥18years with a primary diagnosis of AF. Obese patients were identified using the co-morbidity variable for obesity, as defined in National Inpatient Sample databases. Multivariable logistic regression was used to compare in-hospital outcomes (mortality, acute stroke events) between obese and non-obese patients with AF. Of 431, 734 hospitalizations for AF, 66,138 (15.3%) were obese. Obese patients were younger and more likely to be African-Americans compared with non-obese patients. Despite being younger, obese patients had significantly higher prevalence of cardiovascular co-morbidities such as hypertension, diabetes mellitus, dyslipidemia, smoking, heart failure, and chronic renal failure (p <0.001 for all). After multivariate risk-adjustment, obese patients had a lower observed in-hospital mortality (0.5% vs 1.0%; unadjusted odds ratio = 0.52, 95% confidence interval [CI] 0.46 to 0.58, p <0.001; adjusted odds ratio = 0.83, 95% CI 0.73 to 0.94, p <0.001) and acute stroke events (0.4% vs 0.7%, unadjusted odds ratio = 0. 65, 95% CI 0.57 to 0.73, p < 0.001; adjusted odds ratio = 0.82, 95% CI 0.72 to 0.94) compared with non-obese patients. In conclusion, in this large retrospective analysis of an unselected nationwide cohort of patients hospitalized for AF, obese patients demonstrated lower risk-adjusted odds of in-hospital mortality and stroke events, consistent with an "obesity paradox."

Impact of family history of coronary artery disease on in-hospital clinical outcomes in ST-segment myocardial infarction.

BACKGROUND: Patients with a family history of coronary artery disease (FHxCAD) are at increased risk for development of myocardial infarction (MI). However, the data on the influence of FHxCAD on in-hospital clinical outcomes post ST-segment myocardial infarction (STEMI) is limited. Hence, we evaluated the impact of FHxCAD on in-hospital clinical outcomes post STEMI in an unselected nationwide cohort. METHODS: Nationwide Inpatient Sample (NIS) database [2003-2011] was used to compare differences in all-cause in-hospital mortality and adverse clinical events (cardiogenic shock, acute cerebrovascular events and use of intra-aortic balloon pump) between patients with and without FHxCAD. RESULTS: A total of 2,123,492 STEMI admissions were identified, of which 7.4% (n=158,079) patients were with FHxCAD and 92.6% (n=1,965,413) were without FHxCAD. The FHxCAD group had lower in-hospital mortality [1.4% vs. 8.1%; adjusted odds ratio (OR): 0.42, 95% confidence interval (CI): 0.41-0.44; P<0.001] when compared with no-FHxCAD group. They underwent a significantly higher number of coronary interventions, and were less likely to develop cardiogenic shock, acute cerebrovascular events and to require intra-aortic balloon pump during hospitalization. CONCLUSIONS: This large sample size study demonstrates that STEMI patients with FHxCAD had lower in-hospital mortality and adverse clinical events in comparison to patients with no-FHxCAD. Further research is warranted to determine whether the superior outcomes in FHxCAD patients with STEMI are related to differences in strategies related to diet, exercise, use of medications or coronary interventions.

The potential detrimental effects of calcium channel blockers' overdose and current available management.

Calcium channel blockers (CCBs) are prescribed in a wide variety of cardiovascular conditions. Overdose of this commonly used drug can result in negative physiologic consequences including severe hypotension and even death due to metabolic and hemodynamic compromise. We report the fatal case of an amlodipine overdose, which caused intractable acidosis and cardiovascular failure in a 51-year-old male.