Association between obesity paradox in the all-cause mortality among patients with cardiac resynchronization therapy device.

BACKGROUND: Recent studies have demonstrated an obesity paradox, where obese patients with cardiovascular disease have a better outcome compared to those with normal weight. However, the effect of obesity and body mass index (BMI) on the outcome of patients with cardiac resynchronization therapy (CRT) devices remains unclear. The current study aims to investigate this relationship using all available published data. METHODS: We systematically reviewed studies from Medline and EMBASE databases from inception to January 2024. Eligible studies must investigate the association between BMI status and all-cause mortality in individuals with CRT devices. Relative risk (RR) or hazard ratio (HR) and 95% CIs were retrieved from each study and combined using the generic inverse variance method. RESULTS: A total of 12 cohort studies were included in the meta-analysis. Pooled analysis showed that overweight and obesity patients had lower all-cause mortality compared to those with normal body weight with the pooled risk ratios (RR) for overweight of 0.77 (95% CI 0.69-0.87, I2 47%) and for obesity of 0.81 (95% CI 0.67-0.97, I2 59%). Conversely, the underweight exhibited higher all-cause mortality than the group with normal weight, with a pooled RR of 1.37 (95% CI 1.14-1.64, I2 0%). Additionally, higher BMI as continuous data was associated with decreased all-cause mortality, with a pooled HR of 0.94 (95% CI 0.89-0.98, I2 72%). CONCLUSIONS: The pooled analyses observed an obesity paradox in patients with CRT, where overweight and obesity were associated with reduced all-cause mortality, while underweight individuals exhibited higher all-cause mortality. Further research is necessary to investigate the underlying mechanisms and their implications for clinical practice.

Impact of COVID-19 infection among patients hospitalized for conventional pacemaker implantation: Analysis of the Nationwide Inpatient Sample (NIS) 2020.

Introduction: The cardiac pacemaker is indicated for treating various types of bradyarrhythmia, providing lifelong cardiovascular benefits. Recent data showed that COVID-19 has impacted procedure numbers and led to adverse long-term outcomes in patients with cardiac pacemakers. However, the impact of COVID-19 infection on the in-hospital outcome of patients undergoing conventional pacemaker implantation remains unclear. Method: Patients aged above 18 years who were hospitalized for conventional pacemaker implantation in the Nationwide In-patient Sample (NIS) 2020 were identified using relevant ICD-10 CM and PCS codes. Multivariable logistic and linear regression models were used to analyze pre-specified outcomes, with the primary outcome being in-patient mortality and secondary outcomes including system-based and procedure-related complications. Results: Of 108 020 patients hospitalized for conventional pacemaker implantation, 0.71% (765 out of 108 020) had a concurrent diagnosis of COVID-19 infection. Individuals with COVID-19 infection exhibited a lower mean age (73.7 years vs. 75.9 years, p = .027) and a lower female proportion (39.87% vs. 47.60%, p = .062) than those without COVID-19. In the multivariable logistic and linear regression models, adjusted for patient and hospital factors, COVID-19 infection was associated with higher in-hospital mortality (aOR 4.67; 95% CI 2.02 to 10.27, p < .001), extended length of stay (5.23 days vs. 1.04 days, p < .001), and linked with various in-hospital complications, including sepsis, acute respiratory failure, post-procedural pneumothorax, and venous thromboembolism. Conclusion: Our study suggests that COVID-19 infection is attributed to higher in-hospital mortality, extended hospital stays, and increased adverse in-hospital outcomes in patients undergoing conventional pacemaker implantation.

Hyperpolarization-activated cyclic nucleotide-gated channel inhibitor in myocardial infarction: Potential benefits beyond heart rate modulation.

Myocardial infarction (MI) and its associated complications including ventricular arrhythmias and heart failure are responsible for a significant incidence of morbidity and mortality worldwide. The ensuing cardiomyocyte loss results in neurohormone-driven cardiac remodeling, which leads to chronic heart failure in MI survivors. Ivabradine is a heart rate modulation agent currently used in treatment of chronic heart failure with reduced ejection fraction. The canonical target of ivabradine is the hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in cardiac pacemaker cells. However, in post-MI hearts, HCN can also be expressed ectopically in non-pacemaker cardiomyocytes. There is an accumulation of intriguing evidence to suggest that ivabradine also possesses cardioprotective effects that are independent of heart rate reduction. This review aims to summarize and discuss the reported cardioprotective mechanisms of ivabradine beyond heart rate modulation in myocardial infarction through various molecular mechanisms including the prevention of reactive oxygen species-induced mitochondrial damage, improvement of autophagy system, modulation of intracellular calcium cycling, modification of ventricular electrophysiology, and regulation of matrix metalloproteinases.

Gasdermin D-mediated pyroptosis in myocardial ischemia and reperfusion injury: Cumulative evidence for future cardioprotective strategies.

Cardiomyocyte death is one of the major mechanisms contributing to the development of myocardial infarction (MI) and myocardial ischemia/reperfusion (MI/R) injury. Due to the limited regenerative ability of cardiomyocytes, understanding the mechanisms of cardiomyocyte death is necessary. Pyroptosis, one of the regulated programmed cell death pathways, has recently been shown to play important roles in MI and MI/R injury. Pyroptosis is activated by damage-associated molecular patterns (DAMPs) that are released from damaged myocardial cells and activate the formation of an apoptosis-associated speck-like protein containing a CARD (ASC) interacting with NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), resulting in caspase-1 cleavage which promotes the activation of Gasdermin D (GSDMD). This pathway is known as the canonical pathway. GSDMD has also been shown to be activated in a non-canonical pathway during MI and MI/R injury via caspase-4/5/11. Suppression of GSDMD has been shown to provide cardioprotection against MI and MI/R injury. Although the effects of MI or MI/R injury on pyroptosis have previously been discussed, knowledge concerning the roles of GSDMD in these settings remains limited. In this review, the evidence from in vitro, in vivo, and clinical studies focusing on cardiac GSDMD activation during MI and MI/R injury is comprehensively summarized and discussed. Implications from this review will help pave the way for a new therapeutic target in ischemic heart disease.

Therapeutic potentials of cell death inhibitors in rats with cardiac ischaemia/reperfusion injury.

Growing evidence demonstrated that cell death pathways including ferroptosis, apoptosis and necroptosis contribute to cardiac ischaemia/reperfusion (I/R) injury. We hypothesized that ferroptosis, apoptosis and necroptosis contribute differently to myocardial damage during acute cardiac I/R injury. Rats underwent cardiac I/R or sham operation. I/R-operated rats were divided into 4 groups: vehicle, apoptosis (Z-vad), ferroptosis (Fer-1) and necroptosis (Nec-1) inhibition. Rats in each cell death inhibitor group were subdivided into 3 different dose regimens: low, medium and high. Infarct size, left ventricular (LV) function, arrhythmias and molecular mechanism were investigated. Cardiac I/R caused myocardial infarction, LV dysfunction, arrhythmias, mitochondrial dysfunction, mitochondrial dynamic imbalance, inflammation, apoptosis and ferroptosis. Infarct size, LV dysfunction, mitochondrial dysfunction, apoptosis and ferroptosis were all reduced to a similar extent in rats treated with Z-vad (low and medium doses) or Fer-1 (medium and high doses). Fer-1 treatment also reduced mitochondrial dynamic imbalance and inflammation. No evidence of necroptosis was found in association with acute I/R injury, therefore Nec-1 treatment could not be assessed. Apoptosis and ferroptosis, not necroptosis, contributed to myocardial damage in acute I/R injury. Inhibitors of these 2 pathways provided effective cardioprotection in rats with I/R injury though modulation of mitochondrial function and attenuated apoptosis and ferroptosis.