Treatment of transthyretin cardiac amyloidosis.

PURPOSE OF REVIEW: Tafamidis is currently the only approved disease-modifying treatment for ATTR-CM. However, there have been important developments in the treatment of ATTR-CM, as the results of two phase 3 trials were published and several other trials are in their final stages. In this review, we summarize current and future therapies for ATTR-CM. RECENT FINDINGS: Recently, acoramidis, a TTR stabilizer has been proven to be effective in reducing mortality and morbidity compared to placebo in the ATTRibute-CM trial. Additionally, patisiran, an RNA silencer, preserved functional capacity and quality of life compared to placebo in the APOLLO-B trial. However, the FDA declined to approve patisiran for ATTR-CM. The results of phase 1 trial of ALXN2220, an antiamyloid antibody raise hope for reversal of myocardial damage by amyloid depletion. Phase 3 trials evaluating the efficacy of different RNA silencers, gene editing with CRISPR-Cas9, and other anti-amyloid antibodies are ongoing. SUMMARY: Therapies targeting different mechanism in the pathophysiology of ATTR-CM provide new alternatives for treating patients with ATTR-CM. Future research should focus on comparing their effectiveness, the potential of combined treatment with agents from different classes and on identifying the patients who will benefit most from each class of medication.

SGLT2 inhibitors in heart failure with preserved ejection fraction.

Heart failure (HF) is a clinical syndrome due to either functional or structural impairment of the ventricular pump or filling, representing a major cause of global morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF), characterized by a left ventricular ejection fraction (LVEF) of ≥50%, constitutes over half of the HF population, with a rising prevalence. Until recently, therapeutic options in treating HFpEF and reducing hospitalization and mortality remained limited. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promising results in this patient population. This review article explores current literature and significant clinical trials investigating the impact of sodium- SGLT2 inhibitors in patients with HFpEF.

Sepsis and septic shock outcomes and 90-day readmissions in heart failure with reduced ejection fraction: A national readmission database study.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) are at increased risk for sepsis/septic shock. METHOD: A retrospective study was conducted using the Nationwide Readmission Database (2016-2020). Adult patients admitted with sepsis or septic shock were identified and stratified based on the presence of underlying HFrEF. Multivariable logistic regression assessed the association between HFrEF and in-hospital mortality, 90-day readmission, and other complications. RESULTS: Among 7,326,930 sepsis/septic shock admissions, 6.2 % had HFrEF. HFrEF patients had higher in-hospital mortality (17 % vs. 9.6 %, p < 0.01) and 90-day readmission rates (30.2 % vs. 22.5 %, p < 0.01) compared to those without HFrEF. These differences persisted after adjustment with increased risk of in-hospital mortality (aOR 1.40, 95 %CI 1.38-1.42) and 90-day readmission (aOR 1.15, 95 %CI 1.13-1.16). CONCLUSION: HFrEF patients admitted with sepsis/septic shock have significantly higher rates of in-hospital mortality, complications, and 90-day readmissions compared to those without HFrEF.

Evolution of LDL-C lowering medications and their cardiovascular benefits: Past, present, and future.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Hyperlipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C) is one of the major risk factors for CVD. Major landmark cardiovascular outcome clinical trials demonstrated that LDL-C lowering medications reduce cardiovascular events, and the lower the LDL-C the better the outcome. This article discusses the evolution of LDL-C lowering medications starting from bile acid sequestrants (BAS), statin therapy, bempedoic acid, the proprotein convertase subtilisin kexin 9 (PCSK9) synthesis inhibitor, novel small interfering RNA-based therapy (inclisiran) to the most recent oral PCSK9 inhibitors (MK-0616) which is currently under phase 3 clinical trial studies.