Association between Ranolazine, Ischemic Preconditioning, and Cardioprotection in Patients Undergoing Scheduled Percutaneous Coronary Intervention.

Background and Objectives: Remote ischemic preconditioning (RIPC) has demonstrated efficacy in protecting against myocardial ischemia-reperfusion injury when applied before percutaneous coronary revascularization. Ranolazine, an anti-ischemic drug, has been utilized to minimize ischemic events in chronic angina patients. However, there is a lack of trials exploring the combined effects of ranolazine pretreatment and RIPC in patients undergoing percutaneous coronary interventions (PCIs). Materials and Methods: The present study is a prospective study which enrolled 150 patients scheduled for nonemergent percutaneous coronary revascularization. Three groups were formed: a control group undergoing only PCIs, an RIPC group with RIPC applied to either upper limb before the PCI (preconditioning group), and a group with RIPC before the PCI along with prior ranolazine treatment for stable angina (ranolazine group). Statistical analyses, including ANOVAs and Kruskal-Wallis tests, were conducted, with the Bonferroni correction for type I errors. A repeated-measures ANOVA assessed the changes in serum enzyme levels (SGOT, LDH, CRP, CPK, CK-MB, troponin I) over the follow-up. Statistical significance was set at p < 0.05. Results: The ranolazine group showed (A) significantly lower troponin I level increases compared to the control group for up to 24 h, (B) significantly lower CPK levels after 4, 10, and 24 h compared to the preconditioning group (p = 0.020, p = 0.020, and p = 0.019, respectively) and significantly lower CPK levels compared to the control group after 10 h (p = 0.050), and (C) significantly lower CK-MB levels after 10 h compared to the control group (p = 0.050). Conclusions: This study suggests that combining RIPC before scheduled coronary procedures with ranolazine pretreatment may be linked to reduced ischemia induction, as evidenced by lower myocardial enzyme levels.

Artificial Intelligence in Heart Failure: Friend or Foe?

In recent times, there have been notable changes in cardiovascular medicine, propelled by the swift advancements in artificial intelligence (AI). The present work provides an overview of the current applications and challenges of AI in the field of heart failure. It emphasizes the "garbage in, garbage out" issue, where AI systems can produce inaccurate results with skewed data. The discussion covers issues in heart failure diagnostic algorithms, particularly discrepancies between existing models. Concerns about the reliance on the left ventricular ejection fraction (LVEF) for classification and treatment are highlighted, showcasing differences in current scientific perceptions. This review also delves into challenges in implementing AI, including variable considerations and biases in training data. It underscores the limitations of current AI models in real-world scenarios and the difficulty in interpreting their predictions, contributing to limited physician trust in AI-based models. The overarching suggestion is that AI can be a valuable tool in clinicians' hands for treating heart failure patients, as far as existing medical inaccuracies have been addressed before integrating AI into these frameworks.

Adequacy of thyroid hormone replacement for people with hypothyroidism in real-world settings: A systematic review and meta-analysis of observational studies.

OBJECTIVE: Thyroid hormone under-replacement and over-replacement are associated with adverse health outcomes. This systematic review aimed to evaluate the extent of thyroid hormone replacement adequacy for patients with known hypothyroidism in real-word settings, excluding those receiving thyroid hormone suppressive therapy as thyroid cancer treatment. DESIGN: Four electronic databases (Embase [Ovid], Medline [Ovid], PubMed and SCOPUS) were searched for published and unpublished observational studies until 12 December 2022. The results of the studies were meta-analysed to calculate pooled prevalence estimates for thyroid hormone supplementation adequacy, over-replacement and under-replacement. Quality assessment of studies was performed using the Joanna-Briggs appraisal tool for prevalence studies. RESULTS: Seven studies with a total of 4230 patients were eligible for quantitative synthesis. The pooled prevalence estimates of adequate thyroid replacement, over-replacement and under-replacement were 0.55 (95% confidence interval [CI]: 0.49-0.60, p = .001), 0.20 (95% CI: 0.14-0.27, p = .001) and 0.24 (95% CI: 0.13-0.36, p = .001), respectively. Four studies subclassified hypothyroidism and hyperthyroidism into overt and subclinical. The pooled prevalence of overt and subclinical hyperthyroidism was 0.04 (95% CI: 0.00-0.11, p = .01) and 0.17 (95% CI: 0.09-0.27 p = .001), respectively. For overt and subclinical hypothyroidism, the pooled prevalence was 0.02 (95% CI: 0.01-0.03, p = .001) and 0.20 (95% CI: 0.12-0.29, p = .001), respectively. CONCLUSIONS: On average, approximately half of patients with hypothyroidism are only treated to target euthyroidism. In real-world practice, a significant number of patients are over-treated or under-treated, leading to adverse healthcare outcomes. It is imperative that more effective thyroid monitoring strategies be implemented, with an emphasis on primary care thyroid function monitoring, to minimise inappropriate thyroid replacement treatments and optimise healthcare outcomes at a population level.

Heart Failure in Patients with Chronic Kidney Disease.

The function of the kidney is tightly linked to the function of the heart. Dysfunction/disease of the kidney may initiate, accentuate, or precipitate of the cardiac dysfunction/disease and vice versa, contributing to a negative spiral. Further, the reciprocal association between the heart and the kidney may occur on top of other entities, usually diabetes, hypertension, and atherosclerosis, simultaneously affecting the two organs. Chronic kidney disease (CKD) can influence cardiac function through altered hemodynamics and salt and water retention, leading to venous congestion and therefore, not surprisingly, to heart failure (HF). Management of HF in CKD is challenging due to several factors, including complex interplays between these two conditions, the effect of kidney dysfunction on the metabolism of HF medications, the effect of HF medications on kidney function, and the high risk for anemia and hyperkalemia. As a result, in most HF trials, patients with severe renal impairment (i.e., eGFR 30 mL/min/1.73 m2 or less) are excluded. The present review discusses the epidemiology, pathophysiology, and current medical management in patients with HF developing in the context of CKD.

Larissa Heart Failure Risk Score and Mode of Death in Acute Heart Failure: Insights from REALITY-AHF.

Patients with heart failure (HF) patients may die either suddenly (sudden cardiac death/SCD) or progressively from pump failure. The heightened risk of SCD in patients with HF may expedite important decisions about medications or devices. We used the Larissa Heart Failure Risk Score (LHFRS), a validated risk model for all-cause mortality and HF rehospitalization, to investigate the mode of death in 1363 patients enrolled in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure (REALITY-AHF). Cumulative incidence curves were generated using a Fine-Gray competing risk regression, with deaths that were not due to the cause of death of interest as a competing risk. Likewise, the Fine-Gray competing risk regression analysis was used to evaluate the association between each variable and the incidence of each cause of death. The AHEAD score, a well-validated HF risk score ranging from 0 to 5 (atrial fibrillation, anemia, age, renal dysfunction, and diabetes mellitus), was used for the risk adjustment. Patients with LHFRS 2-4 exhibited a significantly higher risk of SCD (HR hazard ratio adjusted for AHEAD score 3.15, 95% confidence interval (CI) (1.30-7.65), p = 0.011) and HF death (adjusted HR for AHEAD score 1.48, 95% CI (1.04-2.09), p = 0.03), compared to those with LHFRS 0,1. Regarding cardiovascular death, patients with higher LHFRS had significantly increased risk compared to those with lower LHFRS (HR 1.44 adjusted for AHEAD score, 95% CI (1.09-1.91), p = 0.01). Lastly, patients with higher LHFRS exhibited a similar risk of non-cardiovascular death compared to those with lower LHFRS (HR 1.44 adjusted for AHEAD score, 95% CI (0.95-2.19), p = 0.087). In conclusion, LHFRS was associated independently with the mode of death in a prospective cohort of hospitalized HF patients.

The Prognostic Role of Spot Urinary Sodium and Chloride in a Cohort of Hospitalized Advanced Heart Failure Patients: A Pilot Study.

Recent studies have demonstrated the prognostic value of spot urinary sodium (UNa+) in acutely decompensated chronic HF (ADCHF) patients. However, data on the prognostic role of UNa+ and spot urinary chloride (UCl-) in patients with advanced HF are limited. In the present prospective pilot study, we examined the predictive value of UNa+ and UCl- concentration at baseline, at 2 h and at 24 h after admission for all-cause mortality and HF rehospitalization up to 3 months post-discharge. Consecutive advanced HF patients (n = 30) admitted with ADCHF and aged > 18 years were included in the study. Loop diuretics were administered based on the natriuresis-guided algorithm recommended by the recent HF guidelines. Exclusion criteria were cardiogenic shock, acute coronary syndrome, estimated glomerular filtration rate < 15 mL/min/1.73 m2, severe hepatic dysfunction (Child-Pugh category C), and sepsis. UNa+ at baseline (Area Under the Curve (AUC) = 0.75, 95% Confidence Interval (CI) (0.58-0.93), p = 0.019) and at 2 h after admission (AUC = 0.80, 95% CI: 0.64-0.96, p = 0.005) showed good and excellent discrimination, respectively. UCl- at 2 h after admission (AUC = 0.75, 95%CI (0.57-0.93), p = 0.017) demonstrated good discrimination. In the multivariate logistic regression analysis, UNa+ at 2 h (p = 0.02) and dose of loop diuretics at admission (p = 0.03) were the only factors independently associated with the study outcome. In conclusion, UNa+ and UCl- may have a prognostic role in hospitalized advanced HF patients.

COVID-19 and the heart.

An outbreak of coronavirus disease 2019 (COVID-19) occurred in December 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a strain of SARS-CoV. Patients infected with the virus present a wide spectrum of manifestations ranging from mild flu-like symptoms, cough, fever and fatigue to severe lung injury, appearing as bilateral interstitial pneumonia or acute respiratory failure. Although SARS-CoV-2 infection predominantly offends the respiratory system, it has been associated with several cardiovascular complications as well. For example, patients with COVID-19 may either develop type 2 myocardial infarction due to myocardial oxygen demand and supply imbalance or acute coronary syndrome resulting from excessive inflammatory response to the primary infection. The incidence of COVID-19 related myocarditis is estimated to be accountable for an average of 7% of all COVID-19 related fatal cases, whereas heart failure (HF) may develop due to infiltration of the heart by inflammatory cells, destructive action of pro-inflammatory cytokines, micro-thrombosis and new onset or aggravated endothelial and respiratory failure. Lastly, SARS-CoV-2 can engender arrhythmias through direct myocardial damage causing acute myocarditis or through HF decompensation or secondary, through respiratory failure or severe respiratory distress syndrome. In this comprehensive review we summarize the COVID-19 related cardiovascular complications (acute coronary syndromes, myocarditis, HF, arrhythmias) and discuss the main underlying pathophysiological mechanisms.

Acute Myopericarditis after the Second Dose of mRNA COVID-19 Vaccine Mimicking Acute Coronary Syndrome.

Myocarditis is a rare adverse event of vaccination. Recently, mRNA vaccines for COVID-19 have been reported to correlate with myocarditis, specifically in adolescents and young men. We report a rare case of a 50-year-old man who presented with symptoms of myocardial infarction 3 days after the second dose of vaccination for COVID-19. Cardiac magnetic resonance (CMR) imaging revealed acute myopericarditis. Clinicians should be aware of that rare side effect of mRNA vaccines for COVID-19 that can affect not only younger recipients but also middle-aged patients presenting with symptoms mimicking acute coronary syndrome.

Glucose lowering does not necessarily reduce cardiovascular risk in type 2 diabetes.

Diabetes mellitus (DM) is a health condition characterized by glucose dysregulation and affects millions of people worldwide. The presentation of heart failure in diabetic cardiomyopathy extends over a wide phenotypic spectrum, commencing from asymptomatic, subclinical structural abnormalities to severely symptomatic biventricular dysfunction with increased mortality risk. Similarly, the spectrum of systolic dysfunction in diabetic-induced heart failure is diverse. DM leads also to cardiac electrical remodeling reacting on various targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce glucagon and blood glucose levels by raising levels of the endogenous hormones glucagon-like-peptide 1 and glucose-dependent insulinotropic peptide and constitute a safe and effective glucose lowering treatment option in patients with type 2 DM. Despite DPP-4 inhibitors' efficacy regarding glycemic control, their effect on cardiovascular outcomes (myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization, and cardiovascular death) in diabetic patients has been neutral. The potential correlation between atrial flutter and DPP-4 inhibitors administration needs further investigation.

Coexisting Morbidity Burden in Hospitalized Elderly Patients with New-Onset Heart Failure vs Acutely Decompensated Chronic Heart Failure.

Coexisting morbidities (CM) are common in patients with heart failure (HF). This study evaluated the CM burden and its clinical significance in elderly hospitalized patients with new-onset (De-novo) HF (n = 84) and acutely decompensated chronic HF (ADCHF) (n = 122). All had HF symptoms associated with: (a) LVEF <50%, or, (b) left ventricular ejection fraction (LVEF) ≥50% and NT-proBNP ≥300 pg/mL. The primary endpoint was the composite of all-cause death/HF rehospitalization at 6 months. Age was similar between patients with new-onset HF and ADCHF [82 (12.5) vs 80 (11) years, respectively; P = .549]. The CM burden was high in both groups. However, the number of CM [3 (2) vs 4 (1.75)] and the prevalence of multimorbidity [CM ≥2; 65 (77.4%) vs 108 (88.5%)] were lower in new-onset HF (P = .016 and P = .035, respectively). The survival probability without the primary endpoint was higher in new-onset HF than in ADCHF (P = .001) driven by less rehospitalizations (P = .001). In the total study population significant primary endpoint predictors were red blood cell distribution width (RDW), urea, and coronary artery disease (CAD) prevalence (AUC of the model =.7685), whereas significant death predictors were RDW, urea, and the number of CM (AUC = .7859), all higher in ADCHF. Thus, the higher CM burden in ADCHF than in new-onset HF most likely contributed to the worse outcome.

Red blood cell distribution width in elderly hospitalized patients with cardiovascular disease.

BACKGROUND: Red blood cell distribution width (RDW) is elevated in patients with cardiovascular disease (CVD). AIM: To determine RDW values and impact of CV and non-CV coexisting morbidities in elderly patients hospitalized with chronic CVD. METHODS: This prospective study included 204 consecutive elderly patients (age 77.5 [7.41] years, female 94 [46%], left ventricular ejection fraction 53.00% [37.50, 55.00]) hospitalized with chronic CVD at the Cardiology Department of Larissa University General Hospital (Larissa, Greece) from January 2019 to April 2019. Elderly patients were selected due to the high prevalence of coexisting morbidities in this patient population. Hospitalized patients with acute CVD (acute coronary syndromes, new-onset heart failure [HF], and acute pericarditis/myocarditis), primary isolated valvular heart disease, sepsis, and those with a history of blood transfusions or cancer were excluded. The evaluation of the patients within 24 h from admission included clinical examination, laboratory blood tests, and echocardiography. RESULTS: The most common cardiac morbidities were hypertension and coronary artery disease, with acutely decompensated chronic heart failure (ADCHF) and atrial fibrillation (AF) also frequently being present. The most common non-cardiac morbidities were anemia and chronic kidney disease followed by diabetes mellitus, chronic obstructive pulmonary disease, and sleep apnea. RDW was significantly elevated 15.48 (2.15); 121 (59.3%) of patients had RDW > 14.5% which represents the upper limit of normal in our institution. Factors associated with RDW in stepwise regression analysis were ADCHF (coefficient: 1.406; 95% confidence interval [CI]: 0.830-1.981; P < 0.001), AF (1.192; 0.673 to 1.711; P < 0.001), and anemia (0.806; 0.256 to 1.355; P = 0.004). ADCHF was the most significant factor associated with RDW. RDW was on average 1.41 higher for patients with than without ADCHF, 1.19 higher for patients with than without AF, and 0.81 higher for patients with than without anemia. When patients were grouped based on the presence or absence of anemia, ADCHF and AF, heart rate was not increased in those with anemia but was significantly increased in those with ADCHF or AF. CONCLUSION: RDW was elevated in elderly hospitalized patients with chronic CVD. Factors associated with RDW were anemia and CV factors associated with elevated heart rate (ADCHF, AF), suggesting sympathetic overactivity.

Relative contribution of risk factors/co-morbidities to heart failure pathogenesis: interaction with ejection fraction.

AIMS: The relative impact of each individual coexisting morbidity on the pathogenesis of heart failure (HF) is incompletely understood. This study aimed to evaluate the prevalence of individual cardiac and non-cardiac coexisting morbidities both in the overall HF population and in the subgroup of HF patients with a single coexisting morbidity, stratified by left ventricular ejection fraction (LVEF) categories, as a measure of the relative contribution of each co-morbidity to the pathogenesis of HF. METHODS AND RESULTS: This is a prospective, observational study, in which unselected ambulatory patients with chronic HF visiting the HF clinic of a tertiary university hospital from January 2016 to January 2019 were classified according to baseline LVEF into three groups: (i) LVEF < 40%, (ii) LVEF = 40-49%, and (iii) LVEF ≥ 50% and then evaluated for various coexisting morbidities. Overall, 1064 patients (age 73.4 ± 12.1 years, male gender 57.7%, LVEF 43.6 ± 13.9, N-terminal pro-brain natriuretic peptide 2187 ± 710 ng/L, and estimated glomerular filtration rate 67.2 ± 25 mL/min/1.73 m2 ) were recruited in this study. Of these, 361 (33.9%) had an LVEF < 40%, 247 (23.2%) an LVEF = 40-49%, and 456 (42.9%) an LVEF ≥ 50%. There were 90 (8.5%) HF patients with a single coexisting morbidity, 33 (36.7%) with LVEF ≥ 50%, 27 (30.0%) with LVEF = 40-49%, and 30 (33.3%) with LVEF < 40%. Among these patients, those with LVEF ≥ 50% suffered mostly from hypertension (85.7%), whereas the second most common coexisting morbidity was atrial fibrillation (AF) (9.5%). HF patients with LVEF = 40-49% usually suffered from hypertension (35.7%), AF (28.6%), or myocardial infarction (MI) (21.4%). Finally, HF patients with LVEF < 40% usually suffered from MI (30.8%), AF (30.8%), or hypertension (15.4%). CONCLUSIONS: Hypertension is strongly associated with the development of HF with low, intermediate, or near-normal/normal LVEF whereas a history of MI or AF with HF with a low or an intermediate LVEF.

Coexisting Morbidities in Heart Failure: No Robust Interaction with the Left Ventricular Ejection Fraction.

PURPOSE OF REVIEW: Heart failure (HF) patients often present with multiple coexisting morbidities. In this review, we contend that coexisting morbidities are highly prevalent and clinically important regardless of the left ventricular ejection fraction (LVEF). RECENT FINDINGS: Multimorbidity is prevalent in the ambulatory subjects of the community and increases with age. Differences in the prevalence of coexisting morbidities between HF with preserved LVEF (> 50%), mid-range LVEF (40-50%), and reduced LVEF (< 40%) are either not demonstrable or whenever present are small and unrelated to morbidity and mortality. The constellation of coexisting morbidities together with the disease modifiers (age, sex, genes, other) defines the HF phenotype and outcome. There is no robust evidence supporting an interaction in HF patients between the prevalence and clinical significance of coexisting morbidities and the LVEF.

Sudden Arrhythmic Death at the Higher End of the Heart Failure Spectrum.

The risk of sudden cardiac death (SCD) is high in heart failure (HF) patients. Sudden arrhythmic death (SAD) is a frequent cause of exit in HF patients at the lower end of the HF spectrum, and implantable cardioverter-defibrillators have been recommended to prevent these life-threatening rhythm disturbances in select patients. However, less is known regarding the cause of SCD in patients at the upper end of the HF spectrum, despite the fact that the majority of out-of-hospital SCD victims have unknown or near-normal/normal left ventricular ejection fraction (LVEF). In this review, we report the epidemiology, summarize the mechanisms, discuss the diagnostic challenges, and propose a stepwise approach for the prevention of SAD in HF with near-normal/normal LVEF.