Short Versus Long Duration of Dual Antiplatelet Therapy After Second-Generation Drug-Eluting Stents Implantation in Patients with Diabetes.

BACKGROUND: Duration of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) remains uncertain, with increasing data suggestive of acceptable short-term duration. Metabolically accelerated atherosclerosis associated with diabetes makes it essential to study short-term DAPT in this subgroup. With limited studies determining optimal DAPT strategies after second-generation stents in this subset, we aimed to establish the optimal duration of DAPT in the diabetic population using second-generation stents. QUESTION: To determine optimal DAPT duration in diabetic population undergoing PCI in 2nd generation stents. DATA SOURCES: We conducted an electronic database search of randomized controlled trials from PubMed/Medline, Embase, Cochrane, and Web of Science databases. STUDY DESIGN: A meta-analysis was conducted comparing outcomes of short-term (3-6 months) DAPT therapy versus long-term (12 months) DAPT therapy in the diabetic population undergoing PCI with second-generation stents. RESULTS: A total of 5 randomized controlled trials were included with a total of 3117 diabetic patients. Short-term DAPT did not show any statistical difference from long-term DAPT in achieving primary outcomes (relative ratio: 0.96, 95% confidence interval (CI) 0.68-1.35, P = 0.84). Overall mortality (OR 0.92; 95% CI, 0.52-1.63, P = 0.98), myocardial infarction [odds ratio (OR)OR 1.02; 95% CI, 0.53-1.94, P = 0.85], stent thrombosis (OR 1.20; 95% CI, 0.55-2.60, P = 0.55), target vessel revascularization (OR 1.10; 95% CI, 0.45-2.73, P = 0.74), and stroke (OR 0.50; 95% CI, 0.082-2.43, P = 0.81) did not show any statistical difference between the 2 groups. Similarly, a subgroup analysis of study population comparing 6 versus 12 months of DAPT in diabetic population did not show any difference in net primary outcomes (relative ratio: 0.86, 95% CI 0.45-1.45, P = 0.60). There was no significant heterogeneity noted between the 2 groups. CONCLUSION: This meta-analysis showed no statistically significant benefit of longer DAPT over shorter DAPT therapy in patients undergoing PCI with drug-eluting stent in patients with diabetes.

Comparative Safety and Effectiveness of Loading Doses of P2Y12 Inhibitors in Patients Undergoing Elective PCI: a Network Meta-analysis.

PURPOSE: Effective platelet inhibition prior to elective percutaneous coronary intervention (PCI) reduces the risk of ischemic complications. Newer P2Y12 inhibitors are preferred agents over clopidogrel for patients presenting with the acute coronary syndrome. However, the comparative efficacy and safety of them over clopidogrel in elective PCI is unclear. We performed a network meta-analysis to compare the safety and efficacy of loading strategies of P2Y12 inhibitors in patients undergoing elective PCI. METHODS: We conducted a systematic review of randomized controlled trials (RCT) up to June 2021 to compare the safety and effectiveness of different loading strategies of P2Y12 inhibitors before elective PCI. The endpoints of interest were overall mortality, rates of myocardial infarction (MI), stroke, revascularization, and major bleeding. Random effects model using the frequentist approach was used to perform a network meta-analysis using R software. RESULTS: Five trials with a total of 5194 patients were included in our analysis. For ischemic outcomes, including MI, stroke, and revascularization, prasugrel had the most favorable trend. However, clopidogrel had the highest probability of being most effective for major bleeding and all-cause mortality. None of these trends was statistically significant due to lack of power for each outcome. CONCLUSION: Although prasugrel and ticagrelor are known as more potent antiplatelet agents, their effects in preventing MI and stroke are marginal and do not translate into improved overall mortality and bleeding compared with clopidogrel.

Impact of right ventricular impairment on morbidity and mortality in takotsubo syndrome-a meta-analysis of observational trials.

The impact of right ventricular impairment (RVI) on the morbidity and mortality of patients with Takotsubo syndrome (TTS) is well-debated. We conducted a meta-analysis to evaluate the mortality and morbidity risk associated with RVI compared with those without RVI in patients with TTS. A comprehensive search was performed in PubMed and Embase from inception to April 19, 2019. Our primary outcome of interest was in-hospital and long-term mortality. Other outcomes of interest were acute heart failure, left ventricular systolic function, tricuspid and mitral regurgitation, and length of hospital stay (LOS). We are reporting our outcomes as a cumulative odds ratio (OR). After an initial search, 10 studies with 1210 subjects were included in the quantitative analysis. Mean follow-up was 31 months. The odds of in-hospital and long-term mortality in TTS patients with and without RVI were not significantly different (p = 0.13 and 0.40). In TTS patients without RVI, the odds of acute heart failure, and mitral and tricuspid regurgitation were significantly lower at an OR of 0.26 (p < 0.0001), 0.40 (p = 0.0001), and 0.52 (p = 0.02) respectively. TTS patients with RVI had significantly lower mean LVEF (34% vs 41%, p = 0.03) and numerically higher mean LOS (9.5 days vs 7.6 days, p = 0.52) compared with those without RVI. The presence of RVI represents a severe form of TTS disease spectrum, characterized by severely reduced LVEF, higher incidence of MR and presence of TR. Although there was a trend toward increased in-hospital and long-term mortality, RVI in TTS does not portend worse survival.

Hypertension in Cancer Survivors.

PURPOSE OF REVIEW: With increasing survival after cancer treatment, there is a need for long-term management of risk factors and chronic medical conditions to realize the full benefit of improvement of outcomes. Hypertension is a major risk factor for cardiovascular disease and has a higher prevalence in cancer survivors compared to the general population. In this review article, we discuss the burden of hypertension in cancer survivors and how this impacts their long-term outcomes and risk of cancer recurrence. We then discuss the latest concepts regarding the pathophysiology of hypertension in cancer survivors in detail. There is a focus on inflammation and the role it plays in cancer and hypertension followed by a brief discussion on clonal hematopoiesis of indeterminate potential (CHIP) and associated hypertension. There is a brief review of various cancer therapies associated with development and worsening of hypertension control and the underlying mechanisms behind this. We conclude the review article by giving recommendations on blood pressure control in this unique patient population. RECENT FINDINGS: A lot of newer anti-cancer therapies have been implicated in the development or worsening of hypertension. We summarize the latest data, explore associations between these therapies and hypertension, and review the latest understanding of the underlying mechanisms driving this process. Hypertension is a major risk factor for cardiovascular disease in cancer survivors and must be recognized and treated promptly.

Efficacy of Sacubitril/Valsartan in Hypertension.

BACKGROUND: Sacubitril/valsartan (LCZ696) has progressed to be one of the most promising medication since its approval for chronic heart failure with reduced ejection fraction. Recent data have suggested a superior blood pressure control with LCZ696. STUDY QUESTION: What is the antihypertensive efficacy and safety profile of sacubitril/valsartan? DATA SOURCES: Randomized controlled trials (RCTs) comparing the efficacy and safety of LCZ696 against a placebo or angiotensin receptor blocker (ARB). RCTs were identified from a comprehensive search in PubMed, Embase, Cochrane library, and clinicaltrials.gov. STUDY DESIGN: We used a change in systolic and diastolic blood pressures, both sitting as well as ambulatory, to calculate relevant effect sizes with their standard errors from the available change in mean and SD data. In addition, we also collected categorical data for the reported adverse effects from these trials. We performed a series of pairwise meta-analyses between LCZ696 versus an active comparator or a placebo. RESULTS: Eleven RCTs with a total of 6028 participants had the relevant data available. Our meta-analysis showed that LCZ696 is an effective and a safe treatment for hypertension. It outperformed ARBs in every category, and the results are consistent across the different dosages of LCZ696. Compared with ARBs, 200 mg of LCZ696 reduced systolic blood pressure and diastolic blood pressure (DBP) by 4.62 mm Hg (95% confidence interval, 3.33-5.90, P < 0.001) and 2.13 mm Hg (95% confidence interval, 1.69-2.57, P < 0.001), respectively. Similarly, 400 mg of LCZ696 reduced systolic blood pressure and diastolic blood pressure by 5.50 mm Hg (2.94-8.07, P < 0.001) and 2.51 mm Hg (1.80-3.21, P < 0.001), respectively, in comparison with ARBs. The adverse effects with LCZ696 were not significantly higher compared with ARBs or placebo. CONCLUSIONS: Sacubitril/valsartan is more effective for the management of hypertensive patients, compared with an ARB. Long-term prospective studies are required to identify whether this result translates into morbidity and mortality benefits.

Immunotherapy in Bladder Cancer.

BACKGROUND: Bladder cancer is the fifth most common cancer in the United States. Cisplatin-based chemotherapy is the current standard of care in stage IV bladder cancer. It has increased overall survival but rarely results in complete remission, with an overall survival of 14-15 months. The most significant breakthrough in cancer therapy over the last decade was the development of immunotherapy. DATA SOURCES: KEYNOTE-045, IMvigor211, CheckMate275, Javelin Solid Tumor, MEDI4736, and KEYNOTE-0528 clinical trials. AREAS OF UNCERTAINTY: There are ongoing clinical trials using combination of immunotherapy and chemotherapy as first line of therapy in the setting of metastatic urothelial cancer and also to determine the duration of treatment. THERAPEUTIC ADVANCES: Immunotherapy is approved as a second-line treatment for metastatic urothelial cancer. Their use as a first-line agent is only limited to patients who are ineligible for cisplatin-based treatments. Five drugs are approved by Food and Drug Administration for metastatic urothelial cancer including 3 Programmed cell-death protein 1 (PD-1) inhibitors and 2 programmed cell-death ligand 1 (PD-L1) inhibitors in patients who have progressed during or after platinum-based therapy. Pembrolizumab, nivolumab, and atezolizumab are PD-1 inhibitors. Durvalumab and avelumab are PD-L1 inhibitors. However, only 2 drugs were approved based on phase III clinical trials-pembrolizumab and atezolizumab, of which only KEYNOTE study performed with pembrolizumab showed overall survival difference. Atezolizumab and pembrolizumab are the Food and Drug Administration-approved checkpoint inhibitors in cisplatin-ineligible patients. CONCLUSION: This review article summarizes the significance of immunotherapy in treatment of bladder cancer, its side effects, and limitations.

Outcomes of Cardiac Arrest and Cardiopulmonary Resuscitation in Patients With Left Ventricular Assist Device; an Insight From a National Inpatient Sample.

BACKGROUND: Outcomes of patients with implanted left ventricular assist device (LVAD) implantation experiencing a cardiac arrest (CA) are not well reported. We aimed at defining the in-hospital outcomes of patients with implanted LVAD experiencing a CA. METHODS: The national inpatient sample (NIS) was queried using ICD9/ICD10 codes for patients older than 18 years with implanted LVAD and CA between 2010-2018. We excluded patients with orthotropic heart transplantation, biventricular assist device (BiVAD) implantation and do not resuscitate (DNR) status. RESULTS: A total of 93,153 hospitalisations between 2010 and 2018 with implanted LVAD were identified. Only 578 of these hospitalisations had experienced CA and of those, 173 (33%) hospitalisations underwent cardiopulmonary resuscitation (CPR). The mean age of hospitalisations that experienced a CA was 60.61±14.85 for non-survivors and 56.23±17.33 for survivors (p=0.14). The in-hospital mortality was 60.8% in hospitalisations with CA and 74.33% in hospitalisations in whom CPR was performed. In an analysis comparing survivors with non-survivors, non-survivors had more diabetes mellitus (DM) (p=0.01), and ischaemic heart disease (IHD) (p=0.04). Age, female sex, peripheral vascular disease and history of coronary artery bypass graft (CABG) were independently associated with increased mortality in our cohort. Also, ventricular tachycardia (VT) and CPR were independently associated with in-hospital mortality. During the study period, there was a significantly decreasing trend in performing CPR in LVAD hospitalisations with CA. CONCLUSION: In conclusion, age, female sex, peripheral vascular disease, history of CABG, VT and CPR were independently associated with in-hospital mortality in LVAD hospitalisations who experienced CA.

Predictors of permanent pacemaker insertion after TAVR: A systematic review and updated meta-analysis.

OBJECTIVES: The aim of this analysis was to evaluate the predictors associated with increased risk of permanent pacemaker implantation (PPMI) following transcatheter aortic valve replacement (TAVR). BACKGROUND: While TAVR has evolved as the standard of care for patients with severe aortic stenosis, conduction abnormalities leading to the need for PPMI is one of the most common postprocedural complications. METHODS: A systematic literature search was performed to identify relevant trials from inception to May 2020. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. RESULTS: Thirty-seven observational studies with 71 455 patients were identified. The incidence of PPMI following TAVR was 22%. Risk was greater in men and increased with age. Patients with diabetes mellitus, presence of right bundle branch block, baseline atrioventricular conduction block, and left anterior fascicular block were noted to be at higher risk. Other significant predictors include the presence of high calcium volume in the area below the left coronary cusp and noncoronary cusp, use of self-expandable valve over balloon-expandable valve, depth of implant, valve size/annulus size, predilatation balloon valvuloplasty, and postimplant balloon dilation. CONCLUSION: Fourteen factors were found to be associated with increased risk of PPMI after TAVR, suggesting early identification of high-risk populations and targeting modifiable risk factors may aid in reducing the need for this post TAVR PPMI.

Rate, causes, and predictors of 90-day readmissions and the association with index hospitalization coronary revascularization following non-ST elevation myocardial infarction in the United States.

OBJECTIVES: To assess the causes and predictors of readmission after NSTEMI. BACKGROUND: Studies on readmissions following non-ST elevation myocardial infarction (NSTEMI) are limited. We investigated the rate and causes for readmission and the impact of coronary revascularization on 90-day readmissions following a hospitalization for NSTEMI in a large, nationally representative United States database. METHODS: We queried the National Readmission Database for the year 2016 using appropriate ICD-10-CM/PCS codes to identify all adult admissions for NSTEMI. We determined the 90-day readmissions for major adverse cardiac events (MACE). All-cause readmission was a secondary endpoint. The association between coronary revascularization and the likelihood of readmission was analyzed using multivariate Cox regression analysis. RESULTS: A total of 296,965 adult discharges following an admission for NSTEMI were included in this study. The rate of readmissions for MACE was 5.2% (n = 15,637) and for any cause was 18.0% (n = 53,316). 38% of MACE readmissions and 40% of all-cause readmissions occurred between 30- and 90-days following the index hospitalization. During index hospitalization, 51.0% underwent coronary revascularization (40.8% with PCI and 10.2% with CABG). This was independently predictive of a lower risk of 90-day readmission for MACE (adjusted HR 0.59, 95% confidence interval (CI) 0.56-0.63, p < .001) and for any cause (adjusted HR 0.65, 95% CI 0.63-0.67, p < .001). In-hospital mortality for MACE readmissions was significantly higher compared to that of index hospitalization (3.8% vs. 2.6%, p < .001). CONCLUSION: Readmissions following NSTEMI carry higher mortality than the index hospitalization. Coronary revascularization for NSTEMI is associated with a lower readmission rate at 90 days.

30-day readmission following urgent and elective transcatheter aortic valve replacement: A Nationwide Readmission Database analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly used for decompensated severe symptomatic aortic stenosis. Data on urgent and elective TAVR readmission is scarce in the literature. Here, we have performed a retrospective cohort study with the Nationwide Readmission Database of 2016 to identify the rate of 30-day all-cause readmission, common causes of readmission, and distribution of morbidity in index admission and readmission after urgent and elective TAVR. METHODS: We used International Classification of Diseases, Tenth Revision codes (02R.F38H, 02R.F38Z, 02R.F48Z) for identification of all TAVR procedures done in 2016 in patients >18 years old. We found 8379 patients who underwent urgent TAVR and 32,006 patients who underwent elective TAVR in 2016. RESULT: The mean age of patients undergoing urgent TAVR was 79 ± 9.97 years with 44.6% women. The mean age of patients undergoing elective TAVR was 80.7 ± 8.25 years with 46.2% women. We found the 30-day all-cause readmission rate of 15.5% and 9.5% in patients undergoing urgent and elective TAVR, respectively (p < 0.001). The cardiac cause was the predominant cause of readmission in both groups (43.77% vs. 42.11%, p = 0.57), followed by pulmonary cause, gastrointestinal (GI) cause, and renal cause. Among cardiac causes, congestive heart failure (CHF) was predominant cause of readmission and was similar in both groups (18.73 in urgent TAVR vs. 15.73 in elective TAVR, p = 0.12). CONCLUSION: We found that the all-cause 30-day readmission rate was higher in patients who had undergone urgent TAVR. Further studies are needed to better understand this difference.

Approaches for the Management of Resistant Hypertension in 2020.

PURPOSE OF REVIEW: Resistant hypertension is diagnosed if the blood pressure (BP) is not controlled despite optimum doses of 3 first-line classes of antihypertensive drugs including a thiazide diuretic or if adequate BP control needs 4 or more antihypertensive drugs from different classes. RECENT FINDINGS: Pseudohypertension and white coat hypertension must be excluded. Poor patient compliance, inadequate doses of antihypertensive drugs, poor office BP measurement technique, and having to pay for costs of drugs are factors associated with pseudoresistant hypertension. Secondary hypertension must be excluded and treated. Therapy of resistant hypertension includes improving compliance with use of medication, detection, and treatment of secondary hypertension, use of lifestyle measures, and treatment of obesity and other comorbidities. Switching the patient from hydrochlorothiazide to a longer acting thiazide-type diuretic such as chlorthalidone may improve BP control. The beneficial effects of thiazide diuretics are reduced when the glomerular filtration rate is reduced to less than 40 mL/min/1.73 m2. These patients should be treated with a loop diuretic such as furosemide every 12 h. If a fourth antihypertensive drug is needed to control blood pressure in persons treated with adequate doses of antihypertensive drugs from different classes including a thiazide-type diuretic, a mineralocorticoid receptor antagonist should be added to the therapeutic regimen. Further research is needed on investigational drugs and device therapy for treating resistant hypertension. Clinical trials are indicated for the treatment of resistant hypertension by sacubitril/valsartan and also by firibastat.

Impact of weight on the efficacy and safety of direct-acting oral anticoagulants in patients with non-valvular atrial fibrillation: a meta-analysis.

AIMS: This study sought to determine the impact of weight and body mass index (BMI) on the safety and efficacy of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular atrial fibrillation. METHODS AND RESULTS: A systematic literature search was employed in PubMed, Embase, and Cochrane clinical trials with no language or date restrictions. Randomized trials or their substudies were assessed for relevant outcome data for efficacy that included stroke or systemic embolization (SSE), and safety including major bleeding and all-cause mortality. Binary outcome data and odds ratios from the relevant articles were used to calculate the pooled relative risk. For SSE, the data from the four Phase III trials showed that DOACs are better or similarly effective with low BMI 0.73 (0.56-0.97), normal BMI 0.72 (0.58-0.91), overweight 0.87 (0.76-0.99), and obese 0.87 (0.76-1.00). The risk of major bleeding was also better or similar with DOACs in all BMI subgroups with low BMI 0.62 (0.37-1.05), normal BMI 0.72 (0.58-0.90), overweight 0.83 (0.71-0.96), and obese 0.91 (0.81-1.03). There was no impact on mortality in all the subgroups. In a meta-regression analysis, the effect size advantage of DOACs compared with warfarin in terms of safety and efficacy gradually attenuated with increasing weight. CONCLUSION: Our findings suggest that a weight-based dosage adjustment may be necessary to achieve optimal benefits of DOACs for thromboembolic prevention in these patients with non-valvular atrial fibrillation. Further dedicated trials are needed to confirm these findings. PROSPERO 2019 CRD42019140693. Available from: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42019140693.

Comparative Clinical Outcomes of Edoxaban in Adults With Nonvalvular Atrial Fibrillation.

BACKGROUND: A critical appraisal of all pooled evidence regarding novel oral anticoagulants (NOACs) for stroke prevention regardless of publication status or study design has not been conducted yet. Being the latest addition to NOACs, the data on edoxaban are especially scarce. STUDY QUESTION: What are the comparative clinical outcomes of edoxaban versus warfarin and other NOACs apixaban, dabigatran, or rivaroxaban in adults with nonvalvular atrial fibrillation? DATA SOURCES: Randomized controlled trials (RCTs), observational studies, and network meta-analyses were identified in PubMed, EMBASE, the Cochrane Library, Pharmapendium, Elsevier Clinical Pharmacology, and the clinicaltrials.gov trial registry in June 2018. STUDY DESIGN: Rapid review per a priori developed protocol, direct frequentist random-effects meta-analysis of aggregate data, grading the quality of evidence per the Grading of Recommendations Assessment, Development and Evaluation working group approach. RESULTS: Direct 4 RCTs (23,021 patients) suggest that edoxaban is noninferior to warfarin in prevention of stroke and systemic embolism [pooled relative risk (RR): 0.65, 95% confidence interval (CI): 0.23-1.81, 2 RCTs] and reduces the risk of cardiovascular mortality (RR: 0.87, 95% CI: 0.78-0.97, 1 RCT), major cardiovascular morbidity (RR: 0.90, 95% CI: 0.82-0.98, 2 RCTs), and major bleeding events (RR: 0.80, 95% CI: 0.71-0.91, 1 RCT) but increases the risk of gastrointestinal bleeding (RR: 1.21, 95% CI: 1.01-1.46, 1 RCT) and anemia (RR: 1.45, 95% CI: 1.05-1.99, 3 RCTs). Edoxaban is superior to warfarin in patients with increased risk of bleeding with warfarin because of variants in CYP2C9 and VKORC1 genes. Indirect evidence does not allow valid conclusions regarding comparative superiority of NOACs. The quality of evidence was downgraded because of reporting bias, small number of events, and indirectness in comparisons. CONCLUSIONS: Edoxaban is a welcome addition to the NOAC's armamentarium. However, the comparative data with other novel NOACs are mostly nonexisting, and urgently needed for better individual patient assessment.

Comparative Therapeutic Assessment of Atrial Fibrillation in Heart Failure With Reduced Ejection Fraction-A Network Meta-Analysis.

BACKGROUND: Catheter ablation (CA) continues to prove to be an intriguing therapeutic option for the management of atrial fibrillation (AF) especially in patients with heart failure with reduced ejection fraction (HFrEF). Recent data have suggested that CA may be a viable first-line strategy for these patients. STUDY QUESTION: Is CA more effective in managing patients with AF with HFrEF compared to optimal medical treatment and anti-arrhythmic drugs? DATA SOURCES: Randomized controlled trials (RCTs) comparing CA, medical treatment, or antiarrhythmic drugs to each other or a placebo group for the treatment of AF in HFrEF. We performed a comprehensive search in PubMed, Embase, and Cochrane library to identify relevant RCTs. STUDY DESIGN: Our primary outcomes of interest were all-cause mortality, hospitalization for heart failure, and the percentage change in left ventricular ejection fraction. Also, we looked at functional outcomes such as Minnesota Living with Heart Failure Questionnaire and 6-minute walking distance. We used event rates for categorical variables and mean differences between the groups for the continuous variables. We used a frequentist approach employing a graph theory methodology to construct a network meta-analysis model. RESULTS: We ended up with 17 RCTs with 5460 participants and 5 different treatments in our network meta-analysis. Compared to optimal medical therapy, CA was effective in reducing all-cause mortality odds ratio (OR) 0.44 (95% confidence interval, 0.27-0.74; P-value: <0.001) and hospitalization for heart failure OR 0.41 (0.28-0.59; P-value: <0.001). CA also resulted in improvement in left ventricular ejection fraction OR 9.34 (7.13-11.55; P-value: <0.001), Minnesota Living with Heart Failure Questionnaire OR -7.75 (-13.98 to -1.52; P-value: <0.01), and 6MWT OR 27.30 (5.27-49.33; P-value: <0.02). CONCLUSIONS: CA is the most effective and safe treatment for AF patients with HFrEF. We should consider this as a first-line therapy for the management of these patients.

Immune Checkpoint Inhibitors-Related Cardiotoxicity.

BACKGROUND: Immunotherapy is a significant breakthrough in cancer therapy in the last decade. Immunotherapy is better tolerated compared with chemotherapy. However, it does have side effects, and one of the rare and serious side effects of immunotherapy is cardiotoxicity. Cardiotoxicity has been described with other cancer-related treatments such as chemotherapy and targeted therapy. A high index of suspicion is required, and prompt management with immunosuppression needs to be instituted as soon as possible to prevent fatal outcomes. AREAS OF UNCERTAINTY: Research is still ongoing to identify biomarkers that will help us to choose the patients, who will respond well to immunotherapy. Tumor-infiltrating lymphocytes, tumor PD-L1 expression, and tumor mutational burden explored as potential biomarkers. There are no predictive biomarkers to identify patients who are at higher risk of severe cardiotoxicity. Both cardiologists and oncologists should be aware of cardiac toxicity from immune checkpoint inhibitors. CONCLUSION: All patients who are starting immune checkpoint inhibitors should undergo baseline cardiac risk factor assessment with referral to a cardiologist in a patient with multiple risk factors or previous history of cardiovascular disease. Cardiac immune-related adverse events are higher in patients taking combination therapy with anti-CTLA-4/anti-PD-1 agents compared with monotherapy. Patients with known cardiac comorbidities require a higher level of vigilance to monitor for cardiac toxicity because nonspecific symptoms can lead to rapid clinical deterioration and a higher rate of mortality when treated with checkpoint inhibitors.

Advances in the Pharmacogenomics of Antiplatelet Therapy.

BACKGROUND: Acute coronary syndrome (ACS) is a highly thrombotic state, and a sustained antiplatelet effect is vital to the prevention of thrombotic complications. Clopidogrel, the most widely used oral P2Y12 receptor antagonist in ACS, has attracted considerable attention because of significant variability in antiplatelet effect depending on the presence of CYP2C19 allele. Other P2Y12 receptor antagonists offer sustained and more predictable antiplatelet effects than clopidogrel albeit at an increased cost. Several studies have demonstrated the promising application of pharmacogenetics in choosing personalized antiplatelet therapy using the point-of-care genotype assays. AREAS OF UNCERTAINTY: Guidelines regarding the genotype-guided approach to the selection of antiplatelet therapy have been conflicting, and studies evaluating the effect of pharmacogenetic-guided selection of antiplatelet therapy on the outcomes have demonstrated mixed results. DATA SOURCES: A literature search was conducted using MEDLINE and EMBASE for studies reporting the association of pharmacogenetic-guided selection of antiplatelet therapy and the outcomes in patients with ACS until December 2018. RESULTS: Presence of specific CYP2C19 allele significantly influences clopidogrel metabolism and associated outcomes in patients with ACS. Thrombotic and bleeding complications are more common in patients with loss-of-function (LOF) and gain-of-function (GOF) alleles, respectively. Although the pharmacogenetic-guided approach to the selection of antiplatelet therapy appears promising in ACS, studies have shown conflicting results, and direct randomized evidence linking this approach with the better outcomes is lacking. CONCLUSIONS: Genotype-guided selection of antiplatelet therapy is expected to be useful in patients undergoing percutaneous coronary intervention (PCI) with a high risk of adverse outcomes. The patient-physician discussion should be an essential part of this decision-making process. Large-scale multicenter randomized controlled trials using the point-of-care genotype assay are needed to investigate this approach further before its use can be recommended in all comers.

Survival With Continuous Outpatient Intravenous Inotrope Therapy in the Modern Era.

BACKGROUND: To describe baseline characteristics and outcomes in the largest known registry of advanced heart failure (HF) patients receiving continuous outpatient intravenous inotrope therapy. Studies evaluating the use of outpatient inotropes for palliation or as a bridge to advanced therapies were performed before current guideline directed medical and device therapy (GDMDT). There are limited data on the modern experience using outpatient inotrope (OI) therapy. STUDY QUESTION: We aimed to study current use and outcomes of OI. STUDY DESIGN: Retrospective database analysis. MEASURES AND OUTCOMES: From 2015 to 2017, 1540 advanced HF patients in a largess nationwide registry received OI with either milrinone or dobutamine. Baseline characteristics of 1149 patients data were retrospectively reviewed. Unadjusted Kaplan-Meier survival estimates censored at the time of transplant or mechanical circulatory support were reported. RESULTS: Of 1149 patients, more patients were treated with milrinone than dobutamine (64.6% vs. 35.4%). Regardless of the indication for OI, estimated 1 and 2-years survival was 61.8% and 41.6%, respectively. Milrinone use was associated with a greater 1-year survival than dobutamine (70.7% vs. 46.2%, P < 0.0001). The superiority of milrinone over dobutamine extended to all indications for OI, including bridge to transplant (85.9% vs. 71.3%, P < 0.0001), bridge to mechanical support (91.4% vs. 71%, P = 0.001), and palliation (73.6% vs. 63.3%, P < 0.001). After adjusting for indication, age, gender and weight, milrinone was associated with lower mortality than dobutamine (HR 0.50, 95% CI 0.39-0.64, P < 0.0001). CONCLUSIONS: In the largest dataset of HF patients receiving OI, survival on OI for palliation in the current era of GDMDT is significantly higher than previously reported. Compared with dobutamine, milrinone was associated with improved survival in all cohorts.

Efficacy of Upfront Docetaxel With Androgen Deprivation Therapy for Castration-Sensitive Metastatic Prostate Cancer Among Minority Patients.

BACKGROUND: Upfront docetaxel (UD) with androgen deprivation therapy (ADT) has been demonstrated to improve survival outcomes in metastatic castration-sensitive prostate cancer (mCSPC). However, existing studies have included predominantly Caucasian patients. STUDY QUESTION: To compare the efficacy of addition of UD to ADT in mCSPC to ADT alone among minority patients. STUDY DESIGN: Retrospective study of mCSPC patients. MEASURES AND OUTCOMES: Patients treated with UD and ADT between January 2014 and December 2017 (UD + ADT, n = 44) were compared with those treated with ADT alone between January 2008 and January 2017 (ADT, n = 38); patients of Caucasian ethnicity were excluded. The outcome of interest was progression-free survival (PFS), which was estimated using Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: Overall, 63 (76.8%) patients were African American and 16 (19.5%) were Hispanic. Fifty-five (67%) patients had high-volume mCSPC. The median follow-up was 14 months [95% confidence interval (CI): 10.4-16.5] for UD + ADT and 42 months (95% CI: 17-66.9) for ADT. Median PFS did not differ between groups: UD + ADT: 16 versus ADT: 18 months [hazard ratio (HR) for UD + ADT = 0.88, 95% CI: 0.48-1.62; P = 0.70]. In patients with high-volume disease, median PFS remained similar (UD + ADT: 16 vs. ADT: 14 months (HR for UD + ADT = 0.64, 95% CI: 0.33-1.25; P = 0.19). On multivariable analysis, prolonged time to nadir PSA, HR = 0.83 (95% CI: 0.76-0.90), was independently associated with PFS. The most common toxicities in UD + ADT were anemia and fatigue. Major limitations include small sample size and potential for selection bias due to the retrospective study design. CONCLUSIONS: In this retrospective review of a minority mCSPC cohort, UD + ADT was not associated with improved PFS compared with ADT alone. Although further study with larger sample size is needed, these results underscore the importance of ensuring accrual of minorities in clinical trials, reflective of the real-world setting.

Cardiogenic shock during heart failure hospitalizations: Age-, sex-, and race-stratified trends in incidence and outcomes.

The objectives were to study the overall and age-, sex-, and race-stratified incidence of cardiogenic shock (CS) during heart failure hospitalizations (HFHs) not complicated by acute coronary syndromes (ACS), utilization of short-term mechanical circulatory support (MCS) and in-hospital mortality with non-ACS-related CS, and respective temporal trends. Data are lacking regarding the epidemiology of non-ACS-related CS during HFHs. METHODS: Retrospective observational analysis of the National Inpatient Sample 2005-2014 to identify all HFHs in adult patients without concomitant ACS. RESULTS: Of 8,333,752 HFHs, incidence rate of non-ACS-related CS was 8.7 per thousand HFHs (N = 72,668), a 4-fold increase from 4.1 to 15.6 per thousand HFHs between 2005 and 2014 (Ptrend < .001). Among those with non-ACS-related CS, utilization rates of intra-aortic balloon pump, extracorporeal membrane oxygenation, and temporary ventricular assist devices were 12.8%, 1.4%, and 2.5%, respectively. Respective 2005 to 2014 trends were 14.2% to 10.7%, 0.6% to 1.8%, and 0.8% to 2.7% (Ptrend for all, <.001). In-hospital mortality rate was 27.1%, with a substantial decrease from 42.4% in 2005 to 23.3% in 2014 (Ptrend < .001). These temporal trends were largely consistent across age, sex, and race subgroups. CONCLUSION: During HFHs in the United States, non-ACS-related CS occurred infrequently but was associated with substantial mortality. Non-ACS-related CS incidence and certain MCS utilization rates increased, and in-hospital mortality rate decreased between 2005 and 2014. These trends were generally homogenous across the age, sex, and race groups. The observed trends in incidence and mortality may be a reflection of increased identification of CS during HFHs, although further study is needed to assess whether temporal changes in care may have influenced outcomes.

Prevention of Recurrent Ventricular Tachycardia in Patients With Implantable Cardioverter Defibrillators-A Network Meta-analysis.

BACKGROUND: The optimal management for the prevention of recurrent ventricular tachycardia in patients with implantable cardioverter-defibrillators (ICDs) offers a challenge with no set guidelines regarding which therapy offers a best safety and efficacy profile. STUDY QUESTION: Which therapeutic strategy, among antiarrhythmic drugs and catheter ablation (CA), offers the most effective and safe approach in patients with ICDs? DATA SOURCES: Randomized controlled trials (RCTs) comparing the efficacy and safety of antiarrhythmic drugs or CA against a placebo group. RCTs were identified from a comprehensive search in PubMed, Embase, and Cochrane library. STUDY DESIGN: Our outcomes of interest were reductions in appropriate ICD shocks, inappropriate ICD shocks, and overall mortality. We used the event rates in both groups, and then using a frequentist approach employing a graph theory methodology, we constructed a network meta-analysis model. RESULTS: Fourteen RCTs with 3815 participants and 6 different interventions treatments were included in our network meta-analysis. The most effective treatment for the prevention of recurrent ventricular tachycardia after ICD is amiodarone followed by CA. Amiodarone is most effective in the reduction of appropriate and inappropriate ICD shocks with an odds ratio (OR) of 0.29 [95% confidence interval (CI), 0.11-0.74] and 0.15 (95% CI, 0.04-0.60), respectively. CA was effective in the reduction of appropriate ICD shocks (OR, 0.41; 95% CI, 0.20-0.87), whereas sotalol was effective in the reduction of inappropriate ICD shocks (OR, 0.46; 95% CI, 0.22-0.95). There was no significant reduction in the overall mortality from any therapy. There was a trend of increased mortality associated with amiodarone therapy (OR, 2.40; 95% CI, 0.92-6.26). CONCLUSIONS: Amiodarone remains the most efficacious therapy for the reduction of appropriate and inappropriate shocks in patients with ICD. No therapy resulted in mortality reduction, but amiodarone showed a trend toward increased mortality.