Use of percutaneous mechanical circulatory support for right ventricular failure.

BACKGROUND: Utilization of right ventricular mechanical circulatory support (RV-MCS) devices has been limited by a lack of recognition of RV failure as well as a lack of availability and experience with RV-MCS. AIMS: We report a single-center experience with the use of percutaneous RV-MCS and report predictors of adverse outcomes. METHODS: This was a single-center retrospective cohort study. Data from consecutive patients who received RV-MCS for any indication between June 2015 and January 2022 were included. Data on baseline comorbidities, hemodynamics, and laboratory values were collected. The primary outcome was in-hospital mortality analyzed as a logistic outcome in a multivariable model. These variables were further ranked by their predictive value. RESULTS: Among 58 consecutive patients enrolled, the median age was 66 years, 31% were female and 53% were white. The majority of the patients (48%) were hospitalized for acute on chronic heart failure. The majority of the patients were SCAI SHOCK Stage D (67%) and 34 (64%) patients had MCS placed within 24 h of the onset of shock. Before placement of RV-MCS, median central venous pressure (CVP) and RV stroke work index were 20 mmHg and 8.9 g m/m2, respectively. Median serum lactate was 3.5 (1.6, 6.2) mmol/L. Impella RP was implanted in 50% and ProtekDuo in the remaining 50%. Left ventricular MCS was concomitantly used in 66% of patients. Twenty-eight patients (48.3%) died. In these patients, median serum lactate was significantly higher (4.1 [2.3, 13.0] vs. 2.2 [1.4, 4.0] mmol/L, p = 0.007) and a trend toward higher median CVP (24 [18, 31] vs. 19 [14, 24] mmHg, p = 0.052). In the multivariable logistic model, both serum lactate and CVP before RV-MCS placement were independent predictors of in-hospital mortality. Serum lactate had the highest predictive value. CONCLUSION: In our real-world cohort, 52% of patients treated with RV-MCS survived their index hospitalization. Serum lactate at presentation and CVP were the strongest predictors of in-hospital mortality.

Clinical outcomes of intravenous iron therapy in patients with heart failure and iron deficiency: Meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Iron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. METHODOLOGY: We conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. RESULTS: Nine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75-0.93; I2 = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85-0.99; I2 = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. CONCLUSION: In patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.

Current status of global research on pericardial diseases: a bibliometric analysis of the top 100 from Web of Science.

Introduction: Bibliometric studies can help guide researchers and funding bodies toward fields where more research activity is warranted. Bibliometric analyses have previously been published in many specialties and sub-specialties. Our literature search did not show a bibliometric analysis on pericardial diseases. We performed a bibliometric analysis of the top 100 cited manuscripts on pericardial diseases to identify knowledge. Material and methods: Bibliometric analysis is a quantitative method to assess research performance and analyze publication trends. Web of Science was searched in April 2020 to identify the top 100 cited manuscripts in pericardial diseases. Results: Twenty-six out of the top 100 cited manuscripts were published between 2000 and 2009. These manuscripts were cited on average189 times (range: 110-743) since publication. Only two manuscripts were cited > 500 times. Among the top-ten cited manuscripts, there were 6 original articles, 1 case series, and 3 review articles. Of the 3 review articles, 2 were society guidelines. 90% of the authors had written just 1 manuscript. There were ten manuscripts with women as first authors with a significant association between gender of the first and corresponding author (odds ratio = 44, p < 0.001). Only 20% of manuscripts were funded. Most publications came from institutions in the United States (n = 40), Italy (n = 10), and Spain (n = 5). Conclusions: Our study provides an insight into the characteristics and quality of the highly cited literature in the field of pericardial diseases. This can be used to guide further research in the field of pericardial diseases.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 European Society of Cardiology Congress.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 European Society of Cardiology (ESC) congress. RECENT FINDINGS: The NATURE-PARADOX was a naturally randomized trial that used genetic data from the UK Biobank registry to create "cumulative exposure to low-density lipoprotein-cholesterol (LDL-C)" biomarker and evaluate its association with major CV events regardless of plasma LDL-C levels or age. Safety and efficacy data of inclisiran, a PCSK9-interfering mRNA (PCSK9i) administered subcutaneously twice annually, were presented. Data on two new PCSK9is were presented, recaticimab, an oral drug, and lerodalcibep, a subcutaneous drug with a slightly different architecture than currently available PSCK9is. A phase 1 trial on muvalaplin, an oral lipoprotein (a) inhibitor, was presented. An atherosclerotic CV disease (ASCVD) risk prediction algorithm for the Asian population using SCORE2 data was presented. Long-term follow-up of patients enrolled in the CLEAR outcomes trial showed sustained and more significant ASCVD risk reduction with bempedoic acid in high-risk patients. The late-breaking clinical science at the 2023 congress of the ESC extends the known safety and efficacy data of a PCSK9i with the introduction of new drugs in this class. Using cumulative exposure to LDL-C rather than a single value will help clinicians tailor the LDL-C reduction strategy to individual risk and is an important step towards personalized medicine.

Independent prognostic value of high-risk ventricular premature complexes during exercise or recovery in asymptomatic patients: A meta-analysis of observational studies.

INTRODUCTION: Ventricular premature contractions (VPCs) are a common finding during cardiac stress tests. The independent prognostic value of these findings in patients in asymptomatic patients is unclear. METHODS: We conducted a systematic review and meta-analysis of observational studies exploring the independent prognostic value of VPCs to predict all-cause mortality. The secondary outcome was cardiovascular (CV) mortality. We excluded studies that did not report outcomes after adjusting for ≥1 confounder. Random effect meta-analyses were used to predict cumulative hazard ratios. We stratified results based on VPC during exercise or recovery. RESULTS: We found 7 studies with 24,518 patients that met our inclusion criteria. Two studies reported all-cause mortality only, 1 study reported CV mortality only, rest 4 reported both. There was significant heterogeneity in the baseline population, definition of high-risk VPCs, and variables used in adjusted models. Using multivariable summary estimates from individual studies, only VPCs during exercise were associated with a higher risk of all-cause mortality (HR 1.27, 95 % CI 1.07, 1.48). Both VPCs during exercise and recovery were associated with a higher risk CV mortality (HR 1.69, 95 % CI 1.19, 2.20, I2 = 17.6 % and 1.62, 95 % CI 1.25, 2.00, p < 0.001 for both). CONCLUSION: High-risk VPCs during exercise is associated with increased risk of all-cause and CV mortality, while those during recovery are associated with an increased risk of CV mortality only.

The Pandemic of Coronary Heart Disease in South Asia: What Clinicians Need to Know.

PURPOSE OF REVIEW: South Asia has around 1/6th of the current global population. Epidemiological studies suggest that South Asians living in South Asia and diaspora are at an increased risk of premature atherosclerotic cardiovascular diseases (ASCVDs). This is due to an interplay of genetic, acquired, and environmental risk factors. Due to its increasing share of the global population, clinicians need to know the reasons for this early predisposition, and strategies for early identification and mitigation. RECENT FINDINGS: South Asians have earlier onset of cardiometabolic risk factors such as insulin resistance, hypertension, and central adiposity. This increased risk is seen in both native South Asians and the diaspora. South Asians have earlier onset of ASCVD due to an earlier onset of cardiometabolic risk factors. Health promotion and early identification of these risk factors are essential to mitigate this ongoing crisis.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American College of Cardiology Conference.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 American College of Cardiology (ACC) conference. RECENT FINDINGS: The CLEAR outcomes randomized control trial (RCT) compared bempedoic acid to placebo in patients at high-risk of cardiovascular disease (CVD) or prevalent CVD and statin intolerance for CV outcomes. The YELLOW III was a single-arm study that evaluated the effect of Evolocumab on coronary plaque characteristics in patients with stable coronary artery disease (CAD). A cohort evaluated the association between a self-reported low-carbohydrate high-fat (ketogenic) diet and serum lipid levels as compared to a standard diet. The LOADSTAR trial compared CV outcomes with targeted low-density lipoprotein cholesterol (LDL-C) approach vs. high-intensity statin in patients with CAD. The PCDS statin cluster randomized trial compared the effectiveness of an electronic reminder to the clinician on a high-intensity statin use among patients with a history of ASCVD as compared to no reminder. A prospective cohort study compared the extent of coronary atherosclerosis among lifelong endurance athletes and healthy non-athletes. A causal artificial intelligence study combined polygenic risk scores with data from large CV prevention RCTs to guide systolic blood pressure and LDL-C reduction targets to reach average CV risk. The ACCESS trial evaluated the impact of eliminating copayment for low-income older adults in Canada with chronic CV diseases on composite CV outcomes. A pooled analysis of 3 large RCTs evaluated the association between residual inflammatory risk and CV outcomes, as compared to residual elevated cholesterol risk in patients receiving statin therapy. A Phase 2B RCT compared the efficacy of an oral PCSK9i, MK-0616, in reducing LDL-C as compared to a placebo. The late-breaking clinical science presented at the 2023 conference of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2022 American Heart Association Scientific Sessions.

PURPOSE OF REVIEW: Summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2022 scientific session of the American Heart Association (AHA). RECENT FINDINGS: The PROMINENT trial compared pemafibrate to a placebo in patients with type 2 diabetes mellitus (DM) and mild-to-moderate hypertriglyceridemia and high-density lipoprotein cholesterol (HDL-C)<40 mg/dL who were already on guideline-directed statin therapy. The RESPECT-EPA trial compared purified eicosapentaenoic acid (EPA) and statin therapy to statin therapy alone for secondary prevention of atherosclerotic CV disease (ASCVD). SPORT compared the efficacy of low-dose statin therapy with a placebo and six commonly used dietary supplements on lipid and inflammatory markers. Data from long-term follow-up of the FOURIER-OLE study was presented to evaluate the efficacy of very low low-density lipoprotein cholesterol (LDL-C) levels with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Patient-level meta-analyses evaluated the association of statin therapy with new-onset DM and worse glycemic control. PROMPT-LIPID evaluated if automated electronic alerts to physicians with guideline-based recommendations improved the management of hyperlipidemia in patients at very high risk. NOTIFY-1 trial evaluated if notifying physicians and patients about coronary artery calcium (CAC) scores in non-ECG gated computed tomography scans led to increased prescription of statin therapy for primary ASCVD prevention. The DCP trial compared hydrochlorothiazide and chlorthalidone for blood pressure control and CV outcomes in hypertension. The CRHCP study compared the effectiveness of a village doctor for hypertension management and CV outcomes in rural areas of China. The QUARTET USA trial compared the effectiveness and safety of 4 antihypertensive medications in ultra-low doses with angiotensin-receptor blocker monotherapy. The late-breaking science presented at the 2022 scientific session of the AHA paves the way for future pragmatic trials and provides meaningful information to guide management strategies in cardiovascular disease prevention.

Prevalence and Predictors of Premature Coronary Heart Disease Among Asians in the United States: A National Health Interview Survey Study.

Identifying Asian subgroups with higher risk of premature coronary heart disease (CHD) can help implement targeted strategies to prevent future CHD events. We conducted this National Health Interview Survey study from 2006 to 2015 among participants with history of CHD to compare the risk of premature CHD (<65 for women and <55 years old for men) across Whites, Chinese, Asian Indians, Filipinos, and "other Asians" (Japanese, Korean, and Vietnamese individuals) using univariate and multi-variable logistic regression models. A total of 17,266 participants with history of CHD (mean age, 66.0 ± 0.2; 39% women) were included. Risk of premature CHD was higher among Asian Indians (OR = 1.77, 1.05-2.97) and "other Asians" (OR = 1.68, 1.17-2.42) than Whites adults. Compared with Chinese, the risk of premature CHD was significantly higher for Asian Indians in the unadjusted models (OR = 2.72, 1.19-6.3). "Other Asians" exhibited significantly higher risk in crude (OR = 2.88, 1.32-6.27) and adjusted models (aOR = 2.29, 1.01-5.18). Among younger adults (<50 years) with CHD, Asian Indian adults (aOR = 2.43, 1.26-4.70) and other Asian adults (aOR = 1.86, 1.14-3.02) showed higher odds of premature CHD compared with White adults. The risk of premature CHD varies across Asian populations. More studies with an adequate sampling of Asian subgroups are needed to identify the risk and determinants of premature CHD.

Coronary flow abnormalities in chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Coronary vasomotion abnormalities have been described in small studies but not studied systematically. We aimed to review the present literature and analyze it to improve our understanding of chronic kidney disease (CKD) related-coronary microvascular dysfunction. OBJECTIVE: Coronary flow reserve (CFR) is a well-known measure of coronary vasomotion. We aimed to assess the difference in CFR among participants with and without CKD. METHODS: PubMed, Embase, and Cochrane CENTRAL were systematically reviewed to identify studies that compared CFR in participants with and without CKD. We estimated standardized mean differences in mean CFR reported in these studies. We performed subgroup analyses according to imaging modality, and the presence of significant epicardial coronary artery disease. RESULTS: In 14 observational studies with 5966 and 1410 patients with and without CKD, the mean estimated glomerular filtration rate (eGFR) was 29 ± 04 and 87 ± 25 ml/min/1.73 m2 , respectively. Mean CFR was consistently lower in patients with CKD in all studies and the cumulative mean difference was statistically significant (2.1 ± .3 vs. 2.7 ± .5, standardized mean difference -.8, 95% CI -1.1, -.6, p < .05). The lower mean CFR was driven by both significantly higher mean resting flow velocity (.58 cm/s, 95% CI .17, .98) and lower mean stress flow velocity (-.94 cm/s, 95% CI -1.75, -.13) in studies with CKD. This difference remained significant across diagnostic modalities and even in absence of epicardial coronary artery disease. In meta-regression, there was a significant positive relationship between mean eGFR and mean CFR (p < .05). CONCLUSION: Patients with CKD have a significantly lower CFR versus those without CKD, even in absence of epicardial coronary artery disease. There is a linear association between eGFR and CFR. Future studies are required to understand the mechanisms and therapeutic implications of these findings. KEY POINTS: In this meta-analysis of observational studies, there was a significant reduction in coronary flow reserve in studies with chronic kidney disease versus those without. This difference was seen even in absence of epicardial coronary artery disease. In meta-regression, a lower estimate glomerular filtration rate was a significant predictor of lower coronary flow reserve. Coronary microvascular dysfunction, rather than atherosclerosis-related epicardial disease may underly increase cardiovascular risk in a patient with chronic kidney disease.

South Asian ethnicity: What can we do to make this risk enhancer a risk equivalent?

South Asians account for around 25% of the global population and are the fastest-growing ethnicity in the US. This population has an increasing burden of atherosclerotic cardiovascular disease (ASCVD) which is also seen in the diaspora. Current risk prediction equations underestimate this risk and consider the South Asian ethnicity as a risk-enhancer among those with borderline-intermediate risk. In this review, we discuss why the South Asian population is at a higher risk of ASCVD and strategies to mitigate this increased risk.

Necroptosis is associated with Rab27-independent expulsion of extracellular vesicles containing RIPK3 and MLKL.

Extracellular vesicle (EV) secretion is an important mechanism used by cells to release biomolecules. A common necroptosis effector-mixed lineage kinase domain like (MLKL)-was recently found to participate in the biogenesis of small and large EVs independent of its function in necroptosis. The objective of the current study is to gain mechanistic insights into EV biogenesis during necroptosis. Assessing EV number by nanoparticle tracking analysis revealed an increased number of EVs released during necroptosis. To evaluate the nature of such vesicles, we performed a newly adapted, highly sensitive mass spectrometry-based proteomics on EVs released by healthy or necroptotic cells. Compared to EVs released by healthy cells, EVs released during necroptosis contained a markedly higher number of unique proteins. Receptor interacting protein kinase-3 (RIPK3) and MLKL were among the proteins enriched in EVs released during necroptosis. Further, mouse embryonic fibroblasts (MEFs) derived from mice deficient of Rab27a and Rab27b showed diminished basal EV release but responded to necroptosis with enhanced EV biogenesis as the wildtype MEFs. In contrast, necroptosis-associated EVs were sensitive to Ca2+ depletion or lysosomal disruption. Neither treatment affected the RIPK3-mediated MLKL phosphorylation. An unbiased screen using RIPK3 immunoprecipitation-mass spectrometry on necroptotic EVs led to the identification of Rab11b in RIPK3 immune-complexes. Our data suggests that necroptosis switches EV biogenesis from a Rab27a/b dependent mechanism to a lysosomal mediated mechanism.