Early Mechanical Circulatory Support for Cardiogenic Shock.

Reversal of cardiogenic shock depends on its early recognition and prompt initiation of therapy. Recognition of the clinical and hemodynamic deterioration that precedes cardiogenic shock is a crucial step in its early detection. Treatment of pre-cardiogenic shock is chiefly pharmacologic with intravenous administration of pressor, inotropic, and loop diuretic agents. Failure to reverse the preshock state with pharmacotherapy entails progression to cardiogenic shock and the need for prompt mechanical circulatory support with membrane oxygenation and possibly left ventricular decompression.

Colchicine therapy in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Inflammation is a substantial mediator of atherosclerosis. Colchicine has anti-inflammatory effects and has been investigated in many randomized controlled trials (RCTs) in patients with coronary artery disease (CAD). METHODS: We searched PubMed/MEDLINE, Cochrane library, and Embase databases (inception through 28 February 2020) for RCTs evaluating colchicine in CAD patients. The outcomes of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), all-cause mortality, cardiovascular mortality, and stroke. Estimates were pooled using inverse-variance random-effects model. We reported effect sizes as risk difference (RD) with 95% confidence interval (CI). RESULTS: A total of six RCTs with 6154 patients were included. The mean age ± SD for the patients in the colchicine group was 61.6 ± 10.8 and control group was 61.5 ± 10.7 years. At the median follow-up of 3.5 months, use of colchicine in patients with CAD was not associated with statistically significant reduction of MACE (RD -0.032; 95% CI -0.083 to 0.018; P = 0.15; I2 = 75%; low level of evidence), MI (RD -0.011; 95% CI -0.030 to 0.007; P = 0.16; I2 = 11.3%; low level of evidence), all-cause mortality (RD -0.001; 95% CI -0.009 to 0.006; P = 0.65; I2 = 0%; low level of evidence), cardiovascular mortality (RD -0.003; 95% CI -0.010 to 0.004; P = 0.34; I2 = 0%; low level of evidence), and stroke (RD -0.001, 95% CI -0.005 to 0.004; P = 0.69; I2 = 0%; very low level of evidence). CONCLUSION: This meta-analysis suggests that colchicine was not associated with a significant decrease in cardiovascular endpoints and mortality in patients with CAD.

Effect of Progression of Valvular Calcification on Left Ventricular Structure and Frequency of Incident Heart Failure (from the Multiethnic Study of Atherosclerosis).

Heart failure (HF) is a leading cause of morbidity. Strategies for preventing HF are paramount. Prevalent extracoronary calcification is associated with HF risk but less is known about progression of mitral annular (MAC) and aortic valve calcification (AVC) and HF risk. Progression of valvular calcification (VC) [interval change of >0 units/yr] was assessed by 2 cardiac computed tomography scans over a median of 2.4 years. We used Cox regression to determine the risk of adjudicated HF and linear mixed effects models to determine 10-year change in left ventricular (LV) parameters measured by cardiac magnetic resonance imaging associated with VC progression. We studied 5,591 MESA participants free of baseline cardiovascular disease. Mean ± SD age was 62 ± 10 years; 53% women; 83% had no VC progression, 15% progressed at 1 site (AVC or MAC) and 3% at both sites. There were 251 incident HF over 15 years. After adjusting for cardiovascular risk factors, the hazard ratios (95% confidence interval) of HF associated with VC progression at 1 and 2 sites were 1.62 (1.21 to 2.17) and 1.88 (1.14 to 3.09), respectively, compared with no progression (p-for-trend <0.001). Hazard ratios were higher for HFpEF (2.52 [1.63 to 3.90] and 2.49 [1.19 to 5.25]) but nonsignificant for HFrEF. Both AVC (1.61 [1.19 to 2.19]) and MAC (1.50 [1.09 to 2.07]) progression were associated with HF. VC was associated with worsening of some LV parameters over 10 years. In conclusion, VC progression was associated with increased risk of HF and change in LV function. Interventions targeted at reducing VC progression may also impact HF risk, particularly HFpEF.

Effects of Febuxostat on Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To investigate the association between using febuxostat and cardiovascular events. METHODS: Systematic search of randomized controlled trials was performed using PubMed/MEDLINE, Cochrane review, and EMBASE databases through April 17, 2019. Meta-analysis was performed using random effect model and estimates were reported as risk difference (RD) with 95% CIs. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The main outcomes of interest were cardiovascular mortality and all-cause mortality. RESULTS: A total of 15 randomized controlled trials (16,070 participants) were included. The mean ± SD age was 58.1±11.7 years. At the median follow-up of 6.4 months, use of febuxostat was not associated with statistically significant risk of cardiovascular mortality (RD, 0.12%; 95% CI, -0.25% to 0.49%; I 2 =48%; low certainty evidence), all-cause mortality (RD, 0.20%; 95% CI, -0.28% to 0.68%; I 2  =60%; very low certainty evidence), major adverse cardiovascular events (RD, 0.40%; 95% CI, -0.34% to 1.13%; I 2 =26%; low certainty evidence), myocardial infarction (RD, -0.06%; 95% CI, -0.29% to 0.17%; I 2  =0%; moderate certainty evidence), stroke (RD, 0.10%; 95% CI, -0.15% to 0.35%; I 2 =0%; moderate certainty evidence), or new-onset hypertension (RD, 1.58%; 95% CI, -0.63% to 3.78%; I 2 =58%; very low certainty evidence). These findings were consistent in patients with existing cardiovascular disease. CONCLUSION: This meta-analysis suggested that use of febuxostat was not associated with higher risk of mortality or adverse cardiovascular outcomes in patients with gout and hyperuricemia. The results were limited by low to moderate certainty of evidence.

Complete Revascularization in Patients With STEMI and Multi-Vessel Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Percutaneous coronary intervention (PCI) is the treatment of choice for ST-elevation myocardial infarction (STEMI). However, efficacy of complete vs culprit only revascularization in patients with STEMI and multivessel disease remains unclear. METHODS: We searched PubMed/MEDLINE, and Cochrane library. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), repeat revascularization, stroke, major bleeding, and contrast induced nephropathy. Estimates were calculated as random effects hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: Twelve trials with 7592 patients were included. There was a significantly lower risk of MACE [HR 0.61; 95% CI (0.43-0.60); p = 0.0009; I2 = 72%], cardiovascular mortality [HR 0.74; 95% CI (0.56-0.99); p = 0.04; I2 = 2%], and repeat revascularization [HR 0.43; 95% CI (0.31-0.59); p < 0.00001; I2 = 67%] in patients treated with complete compared with culprit-only revascularization. There was no statistically significant difference in MI [HR 0.77; 95% CI (0.52-1.12); p = 0.17; I2 = 49%], all-cause mortality [HR 0.86; 95% CI (0.65-1.13); p = 0.28; I2 = 14%], heart failure [HR 0.82 95% CI (0.51-1.32); p = 0.42; I2 = 26%], major bleeding [HR 1.07; 95% CI (0.66-1.75); p = 0.78; I2 = 25%], stroke [HR 0.67; 95% CI (0.24-1.89); p = 0.45; I2 = 54%], or contrast induced nephropathy, although higher contrast volumes were used in the complete revascularization group [HR 1.22; 95% CI (0.78-1.92); p = 0.39; I2 = 0%]. CONCLUSION: Complete revascularization was associated with a significantly lower risk of MACE, cardiovascular mortality, and repeat revascularization compared with culprit-only revascularization. These results suggest complete revascularization with PCI following STEMI and multivessel disease should be considered.

Transcatheter Aortic Valve Replacement in Low-Risk Patients: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) has become the standard treatment option for patients with symptomatic severe aortic stenosis (AS) with high surgical risk and a reasonable option for intermediate surgical risk as an alternative to surgical aortic valve replacement (SAVR). The role of TAVR in lower risk patients is less established but has been the focus of recent randomized controlled trials (RCTs). We performed a meta-analysis of RCTs to assess TAVR outcomes among low surgical risk patients. METHODS AND RESULTS: Systematic search of RCTs was done using PubMed, EMBASE, and Cochrane Library databases. Statistical analysis was performed with RevMan v5.3 software using a random effects model to report risk ratio (RR) with 95% confidence interval (CI). A total of three RCTs including 2698 patients (1375 TAVR and 1323 SAVR) were analyzed. Compared to SAVR, TAVR was not associated with all-cause mortality [RR 0.86 (95% CI 0.61-1.19); P = 0.36; I2 = 8%] or stroke [RR 0.82 (0.48-1.43); P = 0.49; I2 = 42%]. However, TAVR was significantly associated with lower risk of acute kidney injury [RR 0.27 (0.13-0.54); P = 0.0002; I2 = 0%], new-onset atrial fibrillation [RR 0.26 (0.18-0.39); P < 0.00001; I2 = 80%], and life-threatening or disabling bleeding [RR 0.35 (0.22-0.55); P < 0.00001; I2 = 57%], but a higher risk of moderate-severe paravalvular leak [RR 4.40 (1.22-15.86); P = 0.02; I2 = 26%] and permanent pacemaker insertion [RR 2.73 (1.41-5.28); P = 0.003; I2 = 83%]. CONCLUSIONS: There is no difference in all-cause mortality or stroke between TAVR and SAVR, but TAVR is associated with lower risk of other perioperative complications except for moderate-severe paravalvular leak and the need for permanent pacemaker implantation.

Reliability of focused cardiac ultrasound performed by first-year internal medicine residents at a community hospital after a short training.

The use of bedside ultrasound over the past few decades has created a new wave of options for visualizing pathological processes allowing for faster and better detection of disease. We aimed to evaluate the reliability of focused cardiac ultrasound (FCU) performed by first-year internal medicine residents at a community hospital after a short period of training. They received a two-hour lecture and initially performed a supervised FCU followed by ten unsupervised/independent FCUs each. The four parameters that were assessed were left systolic ventricular function, right systolic ventricular function, presence of pericardial effusion, and presence of IVC dilation. Interpretation and analysis of ultrasound images were then carried out by both the residents and an attending physician with expertise in FCU analysis and interpretation. Cohen's Kappa values were obtained comparing the results found by the interns versus the attending. Our findings indicate that more training is required for reliable analysis of FCU by first-year medical residents. Our results also emphasize the need to carefully evaluate the medical residents' FCU skills after the training.

Strategies in Developing Immunotherapy for Pancreatic Cancer: Recognizing and Correcting Multiple Immune "Defects" in the Tumor Microenvironment.

With the advent of cancer immunotherapies, significant advances have been made in the treatment of many tumor types including melanoma, lung cancer, squamous cell carcinoma of the head and neck, renal cell carcinoma, bladder cancer, etc. However, similar success has not been observed with the treatment of pancreatic cancer and all other immunogenic "cold" tumors. This prompts the need for a better understanding of the complexity of the cold tumor microenvironment (TME) of pancreatic cancer and what are truly the "defects" in the TME making the cancer unresponsive to immune checkpoint inhibitors. Here we discuss four major immune defects that can be recognized in pancreatic cancer, including lack of high-quality effector intratumoral T cells, heterogeneous dense stroma as a barrier to effector immune cells infiltrating into the tumor, immunosuppressive tumor microenvironment, and failure of the T cells to accomplish tumor elimination. We also discuss potential strategies for pancreatic cancer treatment that work by correcting these immune defects.

Managing cardiotoxicity associated with immune checkpoint inhibitors.

Immuno-oncology is a fast evolving field of cancer therapy and immune checkpoint inhibitors (ICIs) are clearly a breakthrough in this field. Cardiotoxicity with conventional anti-cancer therapies has been well studied in the past and clear guidelines for management of these side effects are available in the literature. However, cardiotoxicity with novel agents such as ICIs has been fairly under-reported and/or underestimated and we are yet to formulate clear guidelines for management of these rare side effects. In the last few years, there has been an overall increase in the number of cases of cardiotoxicity related to ICIs. In this literature review, we describe the mechanism of action of the most widely used ICIs and their related cardiotoxicities. The increase in number of case reports about the potential of cardiotoxicities with these novel agents clearly indicates the need for a new insight into the field of cardio-immuno-oncology.