Treatment Of Heart Failure Research Articles

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications

Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications.

Cardiac Surgery 2023 Reviewed.

We reviewed the cardiac surgical literature for 2023. PubMed displayed almost 34,000 hits for the search term "cardiac surgery AND 2023." We used a PRISMA approach for a results-oriented summary. Key manuscripts addressed the mid- and long-term effects of invasive treatment options in patient populations with coronary artery disease (CAD), comparing interventional therapy (percutaneous coronary intervention [PCI]) with surgery (coronary artery bypass graft [CABG]). The literature in 2023 again confirmed the excellent long-term outcomes of CABG compared with PCI in patients with left main stenosis, specifically in anatomically complex chronic CAD, but even in elderly patients, generating further support for an infarct-preventative effect as a prognostic mechanism of CABG. For aortic stenosis, a previous trend of an early advantage for transcatheter (transcatheter aortic valve implantation [TAVI]) and a later advantage for surgical (surgical aortic valve replacement) treatment was also re-confirmed by many studies. Only the Evolut Low Risk trial maintained an early advantage of TAVI over 4 years. In the mitral and tricuspid field, the number of interventional publications increased tremendously. A pattern emerges that clinical benefits are associated with repair quality, making residual regurgitation not irrelevant. While surgery is more invasive, it currently generates the highest repair rates and longest durability. For terminal heart failure treatment, donor pool expansion for transplantation and reducing adverse events in assist device therapy were issues in 2023. Finally, the aortic diameter related to adverse events and technical aspects of surgery dominated in aortic surgery. This article summarizes publications perceived as important by us. It cannot be complete nor free of individual interpretation, but provides up-to-date information for patient-specific decision-making.

404-error "Disease not found": Unleashing the translational potential of -omics approaches beyond traditional disease classification in heart failure research.

The emergence of personalized medicine, facilitated by the progress in -omics technologies, has initiated a new era in medical diagnostics and treatment. This review examines the potential of -omics approaches in heart failure, a condition that has not yet fully capitalized on personalized strategies compared to other medical fields like cancer therapy. Here, we argue that integrating multi-omics technology with systems medicine approaches could fundamentally transform heart failure management, moving away from the traditional paradigm of 'one size fits all'. Our review examines how omics can enhance understanding of heart failure's molecular foundations and contribute to a more comprehensive disease classification. We draw attention to the current state of medical practice that only relies on clinical evidence and a number of standard laboratory tests. At the same time, we propose a shift towards a universal approach that uses quantitative data from multi-omics to unravel complex molecular interactions. The discussion centres around the potential of the transition as a means to enhance individual risk assessment and emphasizes management within clinical settings. While the use of omics in cardiovascular research is not recent, many past studies have focused only on a single omics approach. In order to achieve a better understanding of disease mechanisms, we explore more holistic approaches using genomics, transcriptomics, epigenomics, and proteomics. This review concludes with a call to action to adopt multi-omics in clinical trials and practice to pave the way for more personalized disease management and more effective heart failure interventions.

The Role of SGLT2 Inhibitors on Treatment of Heart Failure, Mode of Actions

The Role of SGLT2 Inhibitors on Treatment of Heart Failure, Mode of Actions

Pacemaker Channels and the Chronotropic Response in Health and Disease

Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease—including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node. During the transition from rest to activity, sympathetic neurons stimulate these cells by activating β-adrenergic receptors and increasing intracellular cyclic adenosine monophosphate. The same signal transduction pathway is targeted by positive chronotropic drugs such as norepinephrine and dobutamine, which are used in the treatment of cardiogenic shock and severe heart failure. The cyclic adenosine monophosphate–sensitive hyperpolarization–activated current (I f ) in pacemaker cells is passed by hyperpolarization-activated cyclic nucleotide-gated cation channels and is critical for generating the autonomous heartbeat. In addition, this current has been suggested to play a central role in the chronotropic effect. Recent studies demonstrate that cyclic adenosine monophosphate–dependent regulation of HCN4 (hyperpolarization-activated cyclic nucleotide-gated cation channel isoform 4) acts to stabilize the heart rate, particularly during rapid rate transitions induced by the autonomic nervous system. The mechanism is based on creating a balance between firing and recently discovered nonfiring pacemaker cells in the sinoatrial node. In this way, hyperpolarization-activated cyclic nucleotide-gated cation channels may protect the heart from sinoatrial node dysfunction, secondary arrhythmia of the atria, and potentially fatal tachyarrhythmia of the ventricles. Here, we review the latest findings on sinoatrial node automaticity and discuss the physiological and pathophysiological role of HCN pacemaker channels in the chronotropic response and beyond.

Discovery of Nelutroctiv (CK-136), a Selective Cardiac Troponin Activator for the Treatment of Cardiovascular Diseases Associated with Reduced Cardiac Contractility.

Cardiac myosin activation has been shown to be a viable approach for the treatment of heart failure with reduced ejection fraction. Here, we report the discovery of nelutroctiv (CK-136), a selective cardiac troponin activator intended for patients with cardiovascular conditions where cardiac contractility is reduced. Discovery of nelutroctiv began with a high-throughput screen that identified compound 1R, a muscle selective cardiac sarcomere activator devoid of phosphodiesterase-3 activity. Optimization of druglike properties for 1R led to the replacement of the sulfonamide and aniline substituents which resulted in improved pharmacokinetic (PK) profiles and a reduced potential for human drug-drug interactions. In vivo echocardiography assessment of the optimized leads showed concentration dependent increases in fractional shortening and an improved pharmacodynamic window compared to myosin activator CK-138. Overall, nelutroctiv was found to possess the desired selectivity, a favorable pharmacodynamic window relative to myosin activators, and a preclinical PK profile to support clinical development.

Rediscovery of the implication of albuminuria in heart failure: emerging classic index for cardiorenal interaction.

The development of new drugs and device therapies has led to remarkable advancements in heart failure (HF) treatment in the past couple of decades. However, it becomes increasingly evident that guideline-directed medical therapy cannot be one-size-fits-all across a wide range of ejection fractions (EFs) and various aetiologies. Therefore, classifications solely relying on EF and natriuretic peptide make optimization of treatment challenging, and there is a growing exploration of new indicators that enable efficient risk stratification of HF patients. Particularly when considering HF as a multi-organ interaction syndrome, the cardiorenal interaction plays a central role in its pathophysiology, and albuminuria has gained great prominence as its biomarker, independent from glomerular filtration rate. Albuminuria has been shown to exhibit a linear correlation with cardiovascular disease and HF prognosis in multiple epidemiological studies, ranging from normal (<30mg/g) to high levels (>300mg/g). However, on the other hand, it is only recently that the details of the pathological mechanisms that give rise to albuminuria have begun to be elucidated, including the efficient compaction/tightening of the glomerular basement membrane by podocytes and mesangial cells. Interestingly, renal disease, diabetes, and HF damage these components associated with albuminuria, and experimental models have demonstrated that recently developed HF drugs reduce albuminuria by ameliorating these pathological phenotypes. In this review, facing the rapid expansion of horizons in HF treatment, we aim to clarify the current understanding of the pathophysiology of albuminuria and explore the comprehensive understanding of albuminuria by examining the clinically established evidence to date, the pathophysiological mechanisms leading to its occurrence, and the outcomes of clinical studies utilizing various drug classes committed to specific pathological mechanisms to put albuminuria as a novel axis to depict the pathophysiology of HF.

Cost-utility analysis of add-on vericiguat for the treatment of chronic heart failure with reduced ejection fraction in China

ObjectiveThis study aimed to evaluate the cost-utility of the addition of vericiguat for treating chronic heart failure (CHF) in China from the healthcare payer’s perspective.MethodsA Markov model was built to estimate the cost and utility of treating CHF using vericiguat plus standard treatment (vericiguat group) vs. standard treatment alone (standard treatment group). The clinical parameters (mortality of cardiovascular and hospitalization rate of HF) were calculated according to the VICTORIA clinical trial. The HF cost and utility data were obtained from the literature published in China. One-way sensitivity analysis and probability sensitivity analysis were performed.ResultsAccording to the 13-year model, vericiguat was more expensive (155599.07 CNY vs. 259396.83 CNY) and more effective (4.41 QALYs vs. 4.54 QALYs). The incremental cost‐utility ratio (ICUR) was 802389.27 CNY per QALY. One-way sensitivity analysis revealed that cardiovascular mortality in the two groups was the parameter that had the greatest impact on the results. The GDP per capita in 2022 in China was 85,700 CNY. The probability sensitivity analysis (PSA) showed that the probability of vericiguat being cost-effective was only 41.7% at the willingness-to-pay (WTP) threshold of 3 times GDP per capita (257,100 CNY).ConclusionsIn China, the treatment of CHF with vericiguat is not cost-effective. The drug price could decrease to 145.8 CNY, which could be considered cost-effective.

Clinical thinking and instrumental diagnostics in the late stage of hypersensitive pneumonitis

The existing inertia of clinical thinking in establishing a diagnosis, even in the presence of instrumental and valid diagnostic criteria, does not always allow for a reconsideration of the diagnosis given to the patient, especially several years ago. Existing clinical recommendations for certain nosological forms, which currently play a decisive role in diagnostics, treatment, and quality assessment of medical services, may not be fully applicable to all patients with a specifi c disease. As an illustration of the above, a clinical example of a patient diagnosed with “bronchial asthma” about 15 years ago without diagnostic criteria for this condition is provided. Three years ago, on a hospitalization described in the article, a chest computed tomography scan revealed typical signs of diff use pulmonary pneumonia. However, this did not allow for a change in the stereotypical diagnostic view and the correct diagnosis and appropriate treatment, including in a specialized pulmonology department. As a result, the disease progressed with the development of complications in the form of severe respiratory and heart failure. Only a reassessment of clinical symptoms, including inspiratory crackles, chest CT scan (diffuse opacity reduction resembling ground glass), and restrictive abnormalities in external respiration function without obstructive components, allowed for a reevaluation of the diagnosis and the prescription of pathogenetic therapy with glucocorticoids in combination with treatment for respiratory and heart failure, leading to rapid clinical improvement.

Obstructive sleep apnea and acute decompensated heart failure

Abstract Funding Acknowledgements None. Background Acute decompensated heart failure is a condition with a high frequency of hospitalizations and mortality. Screening and treatment for obstructive sleep apnea can be helpful in these patients. Purpose To determine the frequency of obstructive sleep apnea in patients with acute decompensated heart failure. To add CPAP home therapy to standard medical treatment for heart failure. To follow patients for 1 year. Methods We conducted a single-centre, prospective cohort study form 150 consecutive patients hospitalized for exacerbation heart failure in the cardiology department. 81 patients meet inclusion criteria – Apnea-Hypopnea index (AHI) &amp;gt; 5, Epworth Sleepiness Scale (ESS) &amp;gt; 8, NYHA class II/III and NTproBNP&amp;gt;900 pg/ml. Patients with OSA were offered to purchase a CPAP device for the home. They were divided into two groups with CPAP and no-CPAP. All patients receiving optimal medical treatment. The follow-up period was 1 year. At the end of the period, patients underwent a physical examination, an echocardiography, and ESS. In the non-CPAP group, 29 patients were followed up and 13 patients dropped out due to mortality. In the CPAP group, 16 patients were followed up, with 1 dropped out. Sleep apnea screening was performed with ApneaLinkTM. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and the E/e‘m ratio. Results From 81 with sleep apnea 72.8% (n=59) has obstructive sleep apnea (OSA) and 27.2% (n=22) has central sleep apnea (CSA). Of the 59 patients with OSA, 17 patients (28.8%) purchased a device and continued therapy at home, while 42 patients (71.2%)on optimal drug therapy without CPAP. There is a statistically significant difference in BMI in the group with CPAP compared to the no-CPAP group at the beginning and at the end of the follow-up (CPAP group at the start 36.47±7.3 vs. the end 33.3±5.7, p=0.001 and no-CPAP group at the start 36.35±7.34 vs. the end 35.74±7.46 , p=0.356). A similar relationship is found in systolic blood pressure(SBP) and diastolic blood pressure(DBP). SBP in CPAP group at start 136.2±6.2 mmHg vs. end 123.1±5.9 mmHg; р&amp;lt;0.001. relative to no-CPAP group – start 131.2±9.8 mmHg vs. end 131.3±7.7 mmHg; р=0.965. DBP in CPAP group at start 85.9±6.7 mmHg vs. end 77.3±5.3 mmHg; р&amp;lt;0.001 and no-CPAP group start 82.1±7.4 mmHg vs. end 81.7±5.7 mmHg, р=0.644. There is a significant change in LVEF between the two groups at the beginning and at the end of the follow-up (in CPAP group at start 47.5±8.7, vs. at end 50.07±7.5; р=0.005, between no-CPAP at start 52.5±6.9 vs. at end 52.2±7.1; р=0.389). The CPAP group had a median survival of 11.7 months vs. 10.1 months in no CPAP group(Log Rank (Mental-Cox) p=0.044 ). Conclusion Obstructive sleep apnea is a common comorbidity in patients with acute decompensated heart failure. The addition of CPAP therapy in these patients improved BMI, SBP, DBP and increases LVEF. All this improves the prognosis for these patients.

Medical treatment of heart failure with RAS inhibitors and beta blockers in aortic stenosis – association to long-term outcome after aortic valve replacement

Abstract Background There is a lack of robust data on optimal medical treatment of heart failure in patients with severe aortic stenosis, with no randomized controlled trials guiding treatment. Objective To study the association between exposure to renin-angiotensin-aldosterone system (RAS) inhibitors or beta-blockers and outcome after aortic valve replacement in patients with aortic stenosis and heart failure. Methods and results The study included all patients with heart failure undergoing aortic valve replacement for aortic stenosis in Sweden between 2008-2016 (n = 4668 patients). Exposure to treatment was assessed by continuous tracking of drug dispensations and outcome events were all-cause mortality and hospitalization for heart failure collected from national patient registries. After adjustment for age, sex, atrial fibrillation, hypertension, diabetes mellitus and prior myocardial infarction Cox regression analysis showed that RAS inhibition was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.58, 95% CI 0.51 - 0.65) and preserved LV-EF (HR 0.69, 95% CI 0.56 - 0.85). Beta-blockade was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.81, 95% CI 0.71–0.92), but not in preserved LV-EF (HR 0.87, 95% CI 0.69 - 1.10). There was no association between RAS inhibition or beta-blockade and the risk of hospitalization for heart failure. Conclusions RAS inhibition was associated with lower all-cause mortality after valve replacement in patients with both reduced and preserved LV-EF. Beta-blockade was associated with lower all-cause mortality only in patients with reduced LV-EF.

Coronary Revascularisation in Heart Failure with Reduced Ejection Fraction

The role of myocardial revascularisation in patients suffering from ischaemic cardiomyopathy with extensive coronary artery disease and heart failure with reduced ejection fraction (HFrEF) remains controversial. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are considered revascularisation procedures. Evidence prior to the latest medical treatment advances only suggests a long-term benefit of CABG over pharmacological therapy in this population. When angina-related symptoms dominate patients’ lives despite optimal medical treatment, PCI can be considered if the patient is ineligible for CABG after carefully weighing up the perioperative risk. Viability and/or ischaemia detection to guide revascularisation have been unable to accurately predict treatment effects of CABG or PCI. Optimal heart failure treatment should be initiated in all patients presenting with ischaemic cardiomyopathy and HFrEF as the first and most important measure to improve long-term prognosis.

Influence of prior myocardial infarction on outcome in patients with ischaemic HFrEF: insights from the EVIdence based TreAtment in Heart Failure (EVITA-HF) registry.

There is scarce information about the influence of prior myocardial infarction (pMI) on outcomes in patients (pts) with ischaemic HFrEF. We analysed data from the EVIdence based TreAtment in Heart Failure (EVITA-HF) registry. EVITA-HF comprises web-based case report data on demography, diagnostic measures, adverse events and 1-year follow-up of patients hospitalized for chronic heart failure ≥ 3months (CHF) and an ejection fraction ≤ 40%. In the present study, we focused on the outcomes of pts with and without pMI in ischaemic HFrEF. Between February 2009 and November 2015, a total of 2075 consecutive pts with ischaemic HFrEF were included from 16 centres in Germany. A total of 81.2% were male, and the mean age was 71years. A total of 61.5% of the pts with ischaemic HFrEF had a history of pMI. These pts were treated less often with PCI (20.0 vs. 31.0%, p < 0.001) or CABG (3.8 vs. 7.7%, p < 0.001). They more often received an ICD (40.9 vs. 28.7%, p < 0.001), but less often a CRT-D (11.3 vs. 19.4%, p < 0.001). After multivariate adjustment, pts with pMI had a greater all-cause mortality after 1year than those without pMI (hazard ratio 1.4; 95% CI, 1.10-1.79, p = 0.007). The combined endpoint of death, resuscitation or ICD shock after 1year was greater in patients with pMI (20.8 vs. 16.4%, p = 0.03). Mobility was more often reduced in pts with pMI (46.8% vs. 40.1%, p = 0.03), and overall health status was more frequently worse in patients with pMI than in those 12months ago (23.1 vs. 15.9%, p = 0.01). More than a quarter of the pts with ischaemic HFrEF were anxious or depressive. pMI in patients with CHF and ischaemic HFrEF was associated with increased mortality, increased event rates, and worsened health status. Hence, the subgroup of pts with ischaemic HFrEF and pMI is at higher risk and deserves special attention.

Interpretation of electrocardiograms and results of daily ECG Holter monitoring in patients with an implanted cardiac contractility modulator

Cardiac contractility modulation (CCM) is a method of non-drug treatment of chronic heart failure (CHF) in patients with no indications for resynchronization therapy. Now, a detailed study of this method and its capabilities is ongoing, and the indications for its use are expanding. As with any other implantable device, it is important to be able to monitor the operation of the CCM, identify its dysfunction and promptly refer patients to specialized institutions. Assessment of the function of CCM- therapy can be carrying out by recording a standard 12‑channel electrocardiogram (ECG), as well as 24‑hour Holter ECG monitoring (HM-ECG). The mechanism of action of CCM-therapy is fundamentally different from that of other implantable devices. Knowledge of the features of the manifestation of CCM-therapy during instrumental studies is necessary for their correct interpretation.

Validation of a New Scoring Method to Assess the Efficacy of Rapid Initiation and Titration of Combination Pharmacotherapy for Patients Hospitalized with Acute Decompensated Heart Failure with Reduced and Mildly Reduced Ejection Fraction

Background: Despite the encouragement of early initiation and titration of guideline-directed medical therapy (GDMT) for the treatment of heart failure (HF), most patients do not receive an adequate type and dose of pharmacotherapy in the real world. Objectives: This study aimed to determine the efficacy of titrating composite GDMT in patients with HF with reduced and mildly reduced ejection fraction and to identify patient conditions that may benefit from titration of GDMT. Methods: This was a two-center, retrospective study of consecutive patients hospitalized with acute decompensated heart failure (ADHF). Patients were classified into two groups according to a scoring scale determined by combination and doses of four types of HF agents (ACEis/ARBs/ARNis, BBs, MRAs, and SGLT2is) at discharge. A score of 5 or greater was defined as titrated GDMT, and a score of 4 or less was regarded as sub-optimal medical therapy (MT). Results: A total of 979 ADHF patients were screened. After 553 patients were excluded based on exclusion criteria, 426 patients (90 patients in the titrated GDMT group and 336 patients in the sub-optimal MT group) were enrolled for the analysis. The median follow-up period was 612 (453–798) days. Following statistical adjustment using the propensity score weighting method, the 2-year composite endpoint (composite of cardiac death and HF rehospitalization) rate was significantly lower in the titrated GDMT group, at 19%, compared with the sub-optimal MT group: 31% (score 3–4 points) and 43% (score 0–2 points). Subgroup analysis indicated a marked benefit of titrated GDMT in particular patient subgroups: age &lt; 80 years, BMI 19.0–24.9, eGFR &gt; 20 mL/min/1.73 m2, and serum potassium level ≤ 5.5 mmol/L. Conclusions: Prompt initiation and dose adjustment of multiple HF medications, with careful monitoring of the patient’s physiologic and laboratory values, is a prerequisite for improving the prognosis of patients with heart failure.

Clinical efficacy of tolvaptan in acute decompensated heart failure patients with severe aortic stenosis and atrial fibrillation: a sub-analysis from the LOHAS registry.

Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4days, comparing patients with AF (AF group) versus those with SR (SR group). There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2kg [p < 0.01] and from 53.5 to 51.0kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2days of treatment with tolvaptan. Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

[Treatment with cardiac electronic implantable devices].

Cardiac device therapy provides not only treatment options for bradyarrhythmia but also advanced treatment for heart failure and preventive measures against sudden cardiac death. In heart failure treatment it enables synergistic reverse remodelling and reduces pharmacological side effects. Cardiac resynchronization therapy (CRT) has revolutionized the treatment of reduced left ventricular ejection fraction (LVEF) and left bundle branch block by decreasing the mortality and morbidity with improvement of the quality of life and resilience. Conduction system pacing (CSP) as an alternative method of physiological stimulation can improve heart function and reduce the risk of pacemaker-induced cardiomyopathy. Leadless pacers and subcutaneous/extravascular defibrillators offer less invasive options with lower complication rates. The prevention of infections through preoperative and postoperative strategies enhances the safety of these therapies.

EFFECT OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES IN HFREF PATIENTS: IMPACT OF DIABETES MELLITUS TYPE 2 STATUS

Dapagliflozin has shown promise in the treatment of heart failure with reduced ejection fraction (HFrEF), but its effects in patients with and without diabetes remain unclear. Objective: This study aimed to assess the effects of dapagliflozin in HFrEF patients, both with and without diabetes. Methods: From January to July 2023, a six-month case-control study was conducted in the cardiology department of a Tertiary Care Hospital in Peshawar, Pakistan. All patients received an additional dose of dapagliflozin (10 mg) alongside their usual treatment plans. The primary outcome was a composite of heart failure exacerbation or cardiovascular death. Data analysis was performed using SPSS version 22. Results: Patients with diabetes mellitus type 2 (DMT2) exhibited a higher rate of cardiovascular death (22%) and hospitalization for heart failure (14.4%) compared to those without diabetes. The hospitalisation rate for heart failure was also higher in the DMT2 group (12.21%) than in the non-diabetic group (8.6%). Over the trial period, cardiovascular death occurred in 12.44% of patients with DMT2 compared to 7.30% in those without DMT2. Patients with diabetes experienced a significantly higher number of first and recurrent hospitalizations for heart failure and cardiovascular death compared to those without diabetes (32.45% vs. 19.20%, p=0.021). Conclusion: Dapagliflozin therapy in HFrEF patients demonstrated varying effects between those with and without diabetes. The study underscores the importance of personalised management strategies considering comorbid medical conditions. Despite dapagliflozin treatment, patients with both heart failure and diabetes continued to experience cardiovascular complications, highlighting the need for individualised treatment plans that account for a patient's complete medical profile.

Rhythm Disorders in Pulmonary Arterial Hypertension (PAH) - What Therapeutic Options are Available?

Rhythm disorders in PAH are rare. In practice, they pose a therapeutic management challenge. Right ventricular dysfunction associated with hypoxia influences the prescription of antiarrhythmics; some of them are even contraindicated. We report three cases of idiopathic PAH complicated by atrial flutter (2 cases) and atrial fibrillation (1 case). The patients experienced right heart failure after a stabilization phase with specific vasodilators (bosentan, sildenafil, iloprost). They were treated with oral amiodarone, alongside treatment for right heart failure. Potassium levels were normal. Beta-blockers were not prescribed due to severe right ventricular dysfunction with arterial hypotension. Unfortunately, two patients developed hyperthyroidism secondary to amiodarone. Through these observations, we will discuss the different therapeutic options in these situations, referencing the literature.

Competing Risks for Monomorphic versus Non-Monomorphic Ventricular Arrhythmias in Primary Prevention Implantable Cardioverter Defibrillator Recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) Study.

Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors of MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. The multicenter retrospective cohort study included 2,668 patients (age 63.1±13.0 y; 23% female; 78% white; 43% nonischemic cardiomyopathy, left ventricular ejection fraction 28.2±11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and ECG metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate ICD therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa (HR 1.16; 95%CI 1.01-1.34), larger SVGel (HR 1.17; 95%CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95%CI 0.63-0.86) and SAIQRST (HR 0.84; 95%CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT (ROC(t)AUC 0.728; 95%CI 0.668-0.788) identified high-risk (> 50%) patients with 75% sensitivity, 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95%CI 0.868-0.962), both satisfactory calibration. We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future RCTs of prophylactic VT ablation.