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Background: Little is known about the epidemiology and prognostic significance of acid-base disturbances in the cardiovascular intensive care unit (CICU). This study examines the association of acid-base status at admission with in-hospital mortality among CICU patients. Methods: We conducted a retrospective analysis of adults admitted to the Mayo Clinic CICU from 2007-2018 who had available blood gas data, utilizing laboratory values obtained closest to the time of CICU admission. Arterial pH, serum bicarbonate, base excess, and partial pressure of carbon dioxide (PaCO 2 ) were examined as predictors of in-hospital mortality. Logistic regression models were used to assess associations, with adjustment for demographics, comorbidities, illness severity, and interventions. A composite acidosis score (CAS, range 0–5), incorporating predefined cut-offs for arterial pH, base excess, and anion gap was calculated to quantify acid-base disturbance severity. Results: A total of 3,229 patients were included for analysis. Of all acid-base variables, acidemia (pH<7.35) emerged as the strongest predictor of in-hospital mortality (adjusted odds ratio [aOR] 1.60, 95% confidence interval [CI] 1.29-1.98, p <0.003). Metabolic acidosis (HCO 3 <20 mEq/L) aOR 1.55, 95% CI 1.24-1.95, p <0.001) and respiratory acidosis (PaCO 2 >45 mmHg, aOR 1.44, 95% CI 1.14-1.81, p =0.002) were associated with worse adjusted in-hospital mortality, whereas alkalemia, metabolic alkalosis, and respiratory alkalosis were not (Fig. 1A-C). After adjustment, lower pH and more negative base excess were associated with higher in-hospital mortality (both p <0.001), whereas HCO 3 and PaCO 2 were not ( p =0.053&p=0.051, respectively; Fig. 2). Patients with combined metabolic and respiratory acidosis had the highest in-hospital mortality (56.3%), followed by patients with isolated or compensated metabolic acidosis (Fig.1D). Patients with severe acidosis (CAS>1) had higher mortality (aOR 2.34, 95% CI 1.88–2.90; p<0.001, Fig. 3AB). In-hospital mortality rose with increasing CAS (aOR 1.36 per point higher, 95% CI 1.26–1.47; p<0.001), with consistent effects across admission diagnoses (Fig. 3C). Conclusions: Acidemia, especially in the context of combined metabolic and respiratory acidosis, strongly predicts in-hospital mortality in the CICU. Incorporating combined acid-base disorders into risk stratification scores may facilitate earlier recognition and prevent progression of hemometabolic shock, thereby improving prognosis.

Background: Hypertension and systemic inflammation are independently associated with adverse cardiovascular outcomes. While hypertension is a known risk factor for left ventricular (LV) hypertrophy, the role of inflammation in LV structural changes remains unclear. It is also uncertain whether concomitant inflammation and hypertension ("inflammatory hypertension") exacerbate LV hypertrophy. Research Question: Is inflammatory hypertension associated with increased LV mass index (LVMI) compared to hypertension without inflammation? Methods: We analyzed baseline data from Black adults enrolled in the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort in Jackson, Mississippi. Inflammation was defined by high sensitivity C-reactive protein (hsCRP) >3 mg/L, and hypertension as systolic blood pressure (SBP) >130 mmHg. Participants were classified into four groups: noninflammatory-normotensive (reference group), noninflammatory-hypertensive, inflammatory-normotensive, and inflammatory-hypertensive. The primary outcome was LVMI, assessed by echocardiography. Associations between groups and LVMI were evaluated using generalized estimating equations to account for familial clustering and adjusted for covariates including age, sex, education, smoking status, body mass index, number of antihypertensive medications, statin use, cholesterol, and diabetes. Results: Among 1,027 participants (mean age 64 ± 8.5 years; 71% women), baseline LVMI differed by inflammation-hypertension status. Compared with the LVMI in noninflammatory-normotensive cohort (n=108; 74.5 g/m 2 [70.4–78.6]), significantly higher LVMI was observed in noninflammatory-hypertensive (n=343; 83.6 g/m 2 [81.3–85.9], p<0.001) and inflammatory-hypertensive groups (n=497; 84.7 g/m 2 [82.8–86.7], p<0.001). There was no statistically significant difference between inflammatory-hypertensive and noninflammatory-hypertensive groups (84.7 vs 83.6 g/m 2 )(p=0.460). The inflammatory-normotensive cohort also did not differ from the reference group (74.9 g/m 2 [70.2–79.5], p=0.901). Secondary analyses using elevated IL-6 to define inflammation yielded similar findings ( Figure 1 ). Conclusion: In individuals with inflammatory hypertension, hypertension appears to be the primary driver of LV hypertrophy. Further studies in larger, diverse populations are needed to definitively evaluate the potential additive effect of inflammatory hypertension on LV remodeling.

Background: We aimed to evaluate the outcomes of patients with confirmed and possible cardiac sarcoidosis who had an ICD implant and identify predictors of ventricular arrhythmias and mortality in this patient population. Methods: We performed a retrospective study patients with a diagnosis of cardiac sarcoidosis (CS) at Mayo Clinic and had an ICD implanted for primary or secondary prevention indication. Adult patients (≥18 years) with a diagnosis of possible or confirmed (biopsy-proven) CS with an ICD implanted between 1993 and 2022 were included. Primary outcomes included sustained ventricular arrhythmia (VT) resulting in a documented appropriate ICD shock and death from any cause. Secondary outcomes included ICD-related complications. Results: We identified 148 patients, in which 23 patients (15.5%) experienced VT events with a total of 160 treated episodes. 4 patients (2.7%) experienced inappropriate ICD shocks (11 episodes). During a median follow up of 3.1 years, 26 patients deceased, and the overall survival was 98% and 77% at 1 and 5 year. Older age, CAD, CKD, paced rhythm and QRS duration were associated with worse survival (Figure 1 – 4) . Device related complications were rare, except for the higher percentage of CHF in patients with VT after implant, however this was not statistically significant. Patients with ICD therapies were younger (53 vs 58 years, p=0.029), had higher LGE burden (26.9 vs 16.3%, p=0.01), and higher percentage of LV mass (26.9 vs 16.3, p=0.011). Multivariate logistic regression model which showed that patients with biopsy proven sarcoidosis had significantly higher odds of VT events (OR: 3.04, 95% CI: 1.02 to 9.08, p = 0.046). In patients with increased LV mass (every 10 g increase), the odds of developing VT increased by 1.49 (95% CI: 1.02 to 2.19, p = 0.041). LV mass and LGE percentage showed fair ability of predicting the outcome by ROC analysis. Youden’s index showed 26 for LV mass and 16% for LGE percent as the optimal cut-off points for predicting VT outcomes (Figure 5) . The sensitivity, specificity, positive predictive value, negative predictive value were 81.8%, 74.1%, 37.5%, 95.6% and 75.4% respectively for an LV mass of 26 grams and 81.8%, 63.8%, 30.0%, 94.9% and 66.7% respectively for an LGE percentage of 16%. Conclusion: LGE burden continues to be a major predictor for VT events in patients with CS. Myocardial tissue burden and electrical abnormalities from CS predict mortality than myocardial function loss.

Introduction: Acoramidis, an oral transthyretin (TTR) stabilizer achieving near-complete (≥90%) TTR stabilization, is now approved in the USA, EU, Japan, and UK for the treatment of TTR amyloid cardiomyopathy (ATTR-CM). In the 30-month phase 3 ATTRibute-CM study, acoramidis reduced all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) vs placebo. Through Month 42 (M42) of the open-label extension (OLE; 30 months ATTRibute-CM + 12 months OLE), the clinical benefit of acoramidis was sustained, resulting in a 36% and 43% risk reduction in ACM and ACM/first CVH, respectively, compared with the placebo to acoramidis group Research Question: Are the long-term clinical benefits of acoramidis on ACM and ACM/first CVH in ATTR-CM over 42 months consistent across patient subgroups? Methods: ATTRibute-CM study design has been previously described. At the end of the 30-month double-blind period, patients enrolled into OLE continued acoramidis or switched from placebo to acoramidis; all patients received open-label acoramidis HCI 800 mg BID. Data cut was performed after 12 months in OLE. Subgroup analysis for ACM and ACM/first CVH through M42 were conducted for randomization stratification factors (genotype, NT-proBNP, and eGFR levels) and other pre-specified subgroups. ACM included death due to any cause, cardiac mechanical assist device placement, and heart transplant. CVH included CV hospitalizations (≥24 h) and urgent visits (<24 h) for decompensated heart failure requiring IV diuretics and was adjudicated by an independent Clinical Events Committee. Results: Overall, 389 patients enrolled in the OLE (263 continuous acoramidis and 126 placebo to acoramidis). The analyses of ACM/first CVH ( Figure 1 ) and ACM ( Figure 2 ) through M42 consistently favored patients initially randomized to acoramidis across all patient subgroups, including those based on sex, age, country, ATTR-CM genotype, baseline NT-proBNP, baseline eGFR, NYHA class, and NAC stage. The largest effect size for the reduction in ACM/first CVH (HR <0.50) was observed in the following subgroups: female, non-Caucasian patients, variant ATTR-CM, or NAC stage 2. Conclusions: The long-term benefit of acoramidis was consistently shown in patients initially randomized to acoramidis treatment compared with placebo to acoramidis switch after 30 months across multiple clinically relevant subgroups, underscoring the importance of early initiation of acoramidis to reduce the long-term risk of ACM or CVH.

Background: One of the most troublesome complications of acute pericarditis is recurrence. Non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine form the cornerstone treatment, with the addition of steroids in cases of incomplete response. Recent evidence also suggests a role for interleukin-1 (IL-1) antagonists in challenging cases of recurrence. However, with an increasing number of potential therapies, our study aims to examine the relative efficacy of these anti-inflammatory treatments for recurrent pericarditis risk reduction. Methods: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in October 2023. We included randomized controlled trials (RCTs) and prospective cohort studies of patients with pericarditis treated with a drug with anti-inflammatory properties compared with those treated with a control. The main outcome evaluated was pericarditis recurrence. Results: A total of 6,831 studies were screened, of which 25 articles were included (14 RCTs and 11 cohort studies) for a total number of patients of 3,561. The mean age across studies was 54.82 years for adults and 9.04 years for children (females = 40.55%). The average follow-up duration was 20.03 months. Bayesian network meta-analysis was performed to calculate risk estimates using a random effects model (Figure 1). Goflikicept, a fusion protein that neutralizes IL-1, showed a significant reduction in recurrent pericarditis rates (OR: 0.00, 95% Credible Limits [Crl]: 0.00-0.08). Similarly, anakinra (OR: 0.01, 95% Crl: 0.00-0.13), rilonacept (OR: 0.02, 95% Crl: 0.00-0.22) and colchicine (OR: 0.35, 95% Crl: 0.19-0.64) were associated with a significant reduction in recurrent pericarditis events. High dose colchicine (OR: 0.70, 95% Crl: 0.13-4.12) was not superior to regular dose colchicine (1 mg vs 0.6 mg twice daily, respectively). Interestingly, there was not enough data to make a meaningful comparison between steroids and control. Conclusion: In our analysis, goflikicept, rilonacept, and anakinra were most effective at reducing recurrent pericarditis rates. However, the evidence is based on a small number of studies. Our analysis also corroborated evidence regarding the efficacy of colchicine in reducing pericarditis recurrence. For a comprehensive analysis of the benefits and harms of anti-inflammatory therapies, larger comparative studies or network meta-analyses of patient-level data are required.

Background: The comparable long-term benefits of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with multivessel disease remains limited in underrepresented populations, particularly in patients with multivessel coronary artery disease and heart failure with severely reduced left ventricular ejection fraction (LVEF <35%). Research Question: Among patients with HF and LVEF < 35% which revascularization strategy (CABG or PCI) provides superior long-term clinical outcomes? Methods: We conducted a systematic review and meta-analysis of observational studies involving patients with ischemic heart disease (IHD), HF and LVEF < 35% undergoing PCI or CABG with a minimum follow-up duration of five years. PubMed, Embase, and Cochrane databases were searched for studies published up to April 15, 2025. We computed hazard ratios (HR) from propensity score matched results. We used Cochrane Review Manager version 9.2.1 for statistical analysis. The primary endpoints of interest included all-cause mortality at 5 to 10 years, repeat revascularization, and all-cause mortality at 10 or more years. Results: We included 8 studies with 12,697 patients (6,187 PCI vs 6,510 CABG). Median follow-up duration ranged from 3.8 to 5.2 years, with the longest reported follow-up up to 13 years. The cumulative, propensity adjusted, incidence of all-cause mortality was significantly lower in the CABG group compared to PCI in 5 to 10 years of follow-up (HR 0.61; 95% CI 0.54-0.69; p<0.001) and ≥ 10 years (HR 0.63; 95% CI 0.53-0.74; p<0.001). Additionally, CABG was associated with a reduced need for repeat revascularization in the 5 to 10 year time frame, with a HR of 0.42 (95% CI 0.22-0.81; p=0.01). Conclusion: In this systematic review and meta-analysis of patients with IHD and an ejection fraction ≤ 35% undergoing revascularization, CABG was associated with a reduction in all-cause mortality at ≥ 5 and ≥ 10 years of follow-up, as compared to PCI.

Introduction: Diabetes mellitus (DM) is strongly associated with metabolic and cardiorenal derangements. Natriuretic peptides (NPs), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) have well-established cardiometabolic and cardiorenal protective effects. We developed a novel bispecific biologic, CRRL 101, which agonizes guanylyl cyclase A (GCA) NP receptors and GLP-1 receptors. In this study, we sought to evaluate the in vitro effects and in vivo impact of CRRL 101 in a DM rat model. Methods: In vitro experiments evaluated the impact of CRRL 101 treatment of GCA receptor transfected human embryonic kidney (HEK) cells and INS-1 rat pancreatic beta cells. In vivo experiments were conducted by inducing DM in Wistar rats (male, 6-8-week-old) by intraperitoneal Streptozotocin (STZ) injection (65 mg/kg). One week after STZ injection, DM was confirmed (fasting blood glucose > 350 mg/dL). Rats were then divided into 3 groups: saline control (n=6), 1 pmol/kg/min CRRL-101 (“1pmol” n= 4), and 10 pmol/kg/min CRRL-101 (“10 pmol” n=5). Treatment was infused for 120 min after which rat blood and urine were collected. Data were analyzed using GraphPad Prism 10.0.0. Results: In vitro, there was a marked increase in cyclic GMP (cGMP) levels (pmol/mL) in HEK treated with 10 -6 M CRRL 101 (mean difference ± SEM:1.603 ± 0.29 p = 0.0048). In INS-1 cells treated with CRRL 101 at 10 -6 M in a 20 mM glucose medium, cAMP levels (pmol/mL) markedly increased (16.7 ± 1.47 vs 23.19 ± 1.51 p=0.0036) and insulin levels (ng/mL) doubled (4.4 ng/mL ± 0.44 vs 9.5 ng/mL ± 0.34 in 20 mM glucose p < 0.0001). Similar increases were observed at lower doses (10 -7 M, 10 -8 M) of CRRL 101. In vivo , after 120 minutes of treatment, mean plasma cGMP levels were 6.5x greater in both groups (mean difference± SEM) (1pmol: 38.89 ± 7.93, p = 0.016; 10pmol: 39.40 ± 4.84 p=0.001). Plasma insulin (ng/mL) more than doubled with both doses (1pmol: 0.39 ± 0.148, p = 0.039; 10 pmol: 0.198 ± 0.051, p = 0.004) with no significant increase with placebo ( 0.03 ± 0.08, p = 0.67). Rate of natriuresis (mEq/min) more than doubled with peptide administration vs placebo (1 pmol: 0.36 ± 0.093 p = 0.014; 10 pmol: 0.38 ± 0.13, p = 0.034). Conclusions: Our novel bispecific biologic, CRRL 101, activates GC-A, increasing plasma cGMP and inducing natriuresis, and stimulates GLP-1R, raising cAMP and plasma insulin. Chronic administration studies to eludicate its therapeutic efficacy are warranted.

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent comorbidity strongly associated with cardiovascular diseases, particularly in patients with aortic dissection (AD). However, the long-term impact of severe OSA on survival and distal aortic remodeling after total arch replacement for acute type A aortic dissection (ATAAD) remains unclear. OBJECTIVES: This study aimed to elucidate the specific long-term prognostic impact of severe OSA in patients undergoing ATAAD repair. METHODS: A total of 86 prospectively collected patients who underwent acute type A aortic dissection repair at Beijing Anzhen Hospital between January 2018 and December 2018 were enrolled in the study. All these patients underwent total aortic arch replacement. All patients underwent sleep monitoring within 90 days postoperatively. The association between severe OSA and major adverse events (MAEs) was analyzed using a multivariable Cox proportional hazards model. Kaplan-Meier survival analysis was performed to assess long-term survival. RESULTS: Of these 86 patients, 22 (25.6%) exhibiting severe OSA and 64 (74.4%) not. Individuals with severe OSA had a notably higher rate of major adverse events (MAEs) compared to those without severe OSA (27.3% vs. 7.8%, P =0.047) and a significantly lower long-term survival rate (81.8% vs. 97.4%, P =0.003). After adjusting for potential confounding variables, severe OSA remained an independent predictor of MAEs (HR=3.7, 95% CI: 1.1–12.4, P =0.032). Imaging follow-ups indicated that patients with severe OSA experienced significantly higher stent-graft distal aortic expansion rates (1.8 mm/year vs. 0.4 mm/year, P =0.030), abdominal aortic expansion rates (2.2 mm/year vs. 0.7 mm/year, P <0.001), and false lumen expansion rates in the descending aorta (2.5 mm/year vs. 0.8 mm/year, P =0.003). Moreover, partial thrombosis of the false lumen was more frequently observed in patients with severe OSA (40.9% vs. 14.1%, P =0.028). Conversely, complete false lumen thrombosis (64.1% vs. 45.5%, P =0.028) and false lumen patency (21.9% vs. 13.6%, P =0.028) were more commonly observed in patients without severe OSA. CONCLUSIONS: Severe OSA is associated with an elevated risk of MAEs and is implicated in abnormal distal aortic expansion and false lumen thrombosis among patients undergoing ATAAD repair. These results highlight the importance role of identifying and managing severe OSA in the long-term postoperative care of patients with ATAAD.

Introduction: Dyslipidemia remains a major driver of cardiovascular disease. Monoclonal antibodies (mAb) that block angiopoietin-like protein 3 (ANGPTL3) lower atherogenic lipids by a mechanism distinct from statins. Earlier evidence centred on the Evinacumab. A new trial now evaluate the investigational antibody SHR-1918. Hypothesis: We hypothesized that treatment with ANGPTL3 mAbs whether evinacumab or SHR-1918 would significantly improve lipid parameters compared to placebo without increasing adverse events. Aims: To Quantify the pooled effect of ANGPTL3 mAbs on low-density lipoprotein cholesterol (LDL-C), Triglycerides, apolipoprotein B (ApoB) and non-high-density lipoprotein cholesterol (non-HDL-C) and Compare efficacy and safety between Evinacumab and SHR-1918 subgroups. Methods: A systematic search of Pubmed, Google Scholar MEDLINE, Embase, and ClinicalTrials.gov untill 1 April 2025 was done and relevant randomised controlled trials (RCT's) comparing ANGPTL3 mAbs with placebo in dyslipidaemic patients were included. Data was extracted on spreadsheet and Data analysis was done in RevMan 5.4. Results: 5 RCT's comprising of 603 patients met inclusion criteria. The pooled analysis showed marked reductions in atherogenic lipids with ANGPTL3 monoclonal antibodies versus placebo, including low-density lipoprotein cholesterol (SMD = –2.73, 95 % CI –4.16 to –1.31, P < 0.001), triglycerides (SMD = –3.54, 95 % CI –4.71 to –2.37, P < 0.001), apolipoprotein B (SMD = –1.98, 95 % CI –2.97 to –1.00, P < 0.001) and non-HDL-C (SMD = –2.89, 95 % CI –4.00 to –1.78, P < 0.001). Sub-group analyses demonstrated directionally consistent lipid lowering for both evinacumab and the newer agent SHR-1918. Adverse-event due to treatment evaluation revealed no significant increase in Adverse events due to treatment (RR = 1.05, 95 % CI 0.87 to 1.27, P = 0.63) or serious events (RR = 1.37, 95 % CI 0.54 to 3.44, P = 0.49), indicating good overall tolerability. Conclusion: monoclonal antibodies targeting ANGPTL3 encompassing both evinacumab and the newer agent SHR-1918 consistently reduced LDL-C, triglycerides, and related lipid markers with a favourable tolerability profile. Further large, long-term studies are needed to fully establish their safety, clinical effectiveness, and potential to improve cardiovascular outcomes.