Israel Medical Association Journal

Background: Despite a significant advance in prevention and treatment of heart failure (HF), patients still struggle with decreased quality of life, high mortality, and recurrent hospitalizations. Several inflammatory cytokines have been widely investigated in the pathogenesis of HF.

Objectives: To investigate the prognostic value of fibrinogen on clinical outcomes of patients admitted with acute HF.

Methods: This retrospective study was based on data of patients hospitalized with acute HF. Demographics, laboratory, and clinical outcomes including length of stay and readmissions were obtained. We compared outcomes of patients with normal (< 430 mg/dl) and high (> 430 mg/dl) fibrinogen levels.

Results: We included 149 patients (mean age 67.6 ± 12.3 years, 73.8% male). In our cohort, 24 (16.1%) had normal fibrinogen (< 430 mg/dl) and 125 (83.9%) had high fibrinogen levels (> 430 mg/dl). Among patients with readmissions for HF, fibrinogen levels were higher (622 ± 136 vs. 470 ± 68, P < 0.001) and were associated with longer hospital stay. Fibrinogen remains an independent risk factor after adjusting to age, diabetes status, and left ventricular ejection fraction.

Conclusions: High fibrinogen levels may predict readmissions in patients with HF.

Background: Significant mitral regurgitation (MR) is associated with less spontaneous echo contrast but its effect on the occurrence of ischemic stroke in patients with atrial fibrillation (AF) is unknown.

Objectives: To examine the association of MR grade and the risk of ischemic stroke (IS) in AF patients with heart failure (HF).

Methods: We investigated 2748 patients with known AF who were hospitalized due to acute decompensated HF. All patients underwent echocardiography during hospitalization. Patients were divided into groups based on the degree of MR (high-grade MR [3–4] vs. no/low-grade MR [0–2]). The primary endpoint was IS during long term follow-up.

Results: Mean age was 79 ± 11 years, 48% were women. After 2 years of follow-up, the cumulative incidence of IS among patients with high-grade MR was significantly lower compared to patients with no/low-grade MR (6% vs. 12%, respectively; P-value = 0.0064). Multivariate Fine and Gray analysis, adjusting for CHA₂DS₂-VASc, and accounting for the competing risk of death and valve intervention, showed the presence of high-grade MR was associated with a significant 50% (P = 0.013) reduction in the risk of IS compared with no/low-grade MR. When added to the CHA₂DS₂-VASc score, MR grade allowed more accurate prediction of IS with an overall improvement of 12% (95% confidence interval 5–17%) using net reclassification index analysis.

Conclusions: Our findings suggest an inverse correlation between MR grade and the risk of stroke among AF patients with HF. These findings may be used for improved risk assessment in this population.

Background: Limited data exist regarding the association between marital status and outcomes among octogenarian and nonagenarian patients with heart failure (HF).

Objectives: To examine the association between marital status and outcomes of octogenarian and nonagenarian patients with HF.

Methods: We conducted a retrospective analysis of 1371 octogenarians and nonagenarians who were hospitalized with HF and enrolled in the multicenter national survey in Israel between March and April 2003. The patients were followed until December 2014. Patients were classified into married (n=562) and unmarried (n=809). The clinical characteristics of the patients by marital status categories were compared by using Student's t-test for continuous variables and the chi-square test for categorical variables. Kaplan–Meier survival analysis was used to present survival estimates according to the different marital status categories and the subsequent 4-year survival probability. Multivariate stepwise Cox proportional hazard regression modeling was used to assess the independent predictors of mortality among the study population.

Results: Married patients were more likely to be male, to smoke, and to have past myocardial infarction and previous revascularization. They tended to have higher rates of peripheral vascular disease and dyslipidemia. Survival analysis showed that 4-year mortality rates were similar between married and unmarried patients. The main consistent independent predictors of 4-year mortality were age, advanced HF (New York Heart association (NYHA) > 2), advanced renal failure, low hemoglobin, high Charlson Comorbidity Index, and low admission systolic blood pressure.

Conclusions: Among the octogenarian and nonagenarian population with HF, being unmarried does not confer an increased risk of mortality. Nevertheless, unmarried patients had a different clinical profile. Higher risk profile, co-morbidities, and advanced age impact mortality among octogenarian and nonagenarian patients.

Background: Functional mitral and tricuspid regurgitation (fMR and fTR, respectively) portend increased morbidity and mortality among heart failure (HF) patients.

Objectives: To characterize acute decompensated valvular HF (VHF) as a novel HF category, defined by presence of either more than moderate fTR or more than moderate fMR with left ventricular ejection fraction (LVEF) ≤ 50%.

Methods: Patients with VHF were prospectively enrolled over a 6-month period and compared to acute decompensated heart failure (ADHF) patients without significant fTR or fMR. We used a standardized diuretic protocol when indicated, and appropriate inpatient guideline-directed medical therapy was initiated.

Results: Among 322 patients admitted with ADHF, 83 (26%) met VHF criteria with mean age 66 ± 13 years, 43 (52%) males, and median LVEF of 30% (20–55). Of 61 patients in whom the diuretic protocol was initiated, 59 (97%) had an adequate response (i.e., > 100 cc/hour for at least 6 hours). VHF patients had longer length of hospitalization (8 [5–13] vs. 5 [3–8] days, P < 0.001), and higher rates of 90–day heart replacement therapy (HRT) or death (hazard ratio 2.52, 95% confidence interval (1.13–5.64); P = 0.024).

Conclusions: Over a quarter of ADHF patients can be newly categorized as VHF patients, distinguished by prolonged hospitalization and worse 90-day mortality / HRT rate. The initial response rate to a standardized diuretic protocol was high.

Background: Initiating oral antidiabetic therapy, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, is generally not recommended during hospitalization. However, guidelines since 2021 have supported their use in heart failure with reduced ejection fraction (HFrEF), and since 2023 in preserved ejection fraction (HFpEF).

Objectives: To assess the safety and outcomes of initiating SGLT2 inhibitors during hospitalization for acute heart failure (HF).

Methods: We conducted a historical cohort study of 307 patients admitted with acute HF between October 2018 and April 2022. Patients were grouped as chronic SGLT2i users, new initiators during hospitalization, or controls who did not receive SGLT2i.

Results: Among the 307 patients, 50.4% had HFrEF, 30.8% HFpEF, and 18.8% HF with mildly reduced ejection fraction. In-hospital mortality was 3.6% (11 patients); 2-year mortality was 37.7% (116 patients). New SGLT2i initiators had the lowest 2-year mortality (22.2%) compared to controls (43.9%) and chronic users (41.8%) (P = 0.008). They also had the lowest 1-year rehospitalization rates (18.3% vs. 35.5% vs. 32.8%; P = 0.025). Multivariable analysis identified older age and co-morbidities as independent predictors of mortality. SGLT2i initiation was associated with reduced rehospitalization. Adverse effects occurred in 15.6% of SGLT2i users, mainly acute kidney injury.

Conclusions: In-hospital SGLT2 inhibitor initiation in patients with HF appears safe and is associated with reduced post-discharge mortality and readmission rates.

Background: The prognostic significance of diabetes mellitus (DM) on hospitalization outcomes of patients with acute decompensated heart failure (ADHF) remains inconclusive.

Objectives: To comprehensively assess the clinical outcomes of patients with and without DM hospitalized for ADHF.

Methods: This single center retrospective cohort study included consecutive hospitalized patients with a principal diagnosis of ADHF between 1 January 2010 and 31 December 2019. Patients were categorized into diabetic and non-diabetic groups. The primary outcomes assessed were in-hospital mortality, 1-year overall mortality, and readmission rate within a year of follow-up.

Results: The final analysis involved 787 ADHF patients, with 62% having a pre-existing diagnosis of DM. Despite a higher burden of co-morbidities in diabetic patients, there were no differences in clinical outcomes when compared to non-diabetic counterparts. Specifically, there were no differences in overall hospital mortality (10% vs. 10%, P = 0.675), 1-year mortality (22% vs. 25%, P = 0.389), and re-admissions (51% vs. 56%, P = 0.154). Notably, the 1-year mortality among diabetic patients was not influenced by HbA1c levels documented before or during admission.

Conclusions: The clinical outcomes of patients hospitalized with ADHF did not differ by the presence of diabetes. Instead, our findings emphasize the importance of early heart failure prevention and subsequent hospitalization. Considering the evolving landscape of disease-modifying therapies for heart failure, achieving this goal becomes increasingly feasible.

Background: Cardiovascular disease (CVD) events are rare in premenopausal women. Nevertheless, women with depression have a higher prevalence of CVD. Patients with depression present with endothelial dysfunction and impaired ability to regenerate endothelial progenitor cells (EPCs).

Objectives: To understand the association between depression and CVD, especially in young women.

Methods: We collected peripheral blood samples from 30 premenopausal women diagnosed with major depression and 28 aged-matched healthy women. From these blood samples, we extracted RNA and conducted RNA sequencing to obtain comprehensive gene expression profiles. Gene expression analysis was performed to identify differences between the two groups.

Results: We detected 6540 differentially expressed genes between the two groups, of which 5577 were downregulated and 963 up regulated. Of these genes, we detected a significant decrease of CD144 (VE-Cadherin) (P = 0.0001), CD146 (MCAM) (P = 0.0001) and CD133 (PROM1) (P = 0.00009), all known to enhance EPCs and regeneration of damaged blood vessels. A significant increase was found in the expression of CD31 (PECAM1) (P = 0.0003) and CD45 (PTPRC) (P = 0.00001), both known to promote atherogenesis and thrombogenesis with platelet and T lymphocyte activation.

Conclusions: Young premenopausal women with depression had an impaired ability to grow colony forming units of endothelial progenitor cells (CFU-EPCs). Young women with depression are more vulnerable genetically to develop CVD because of the downregulated genes of the stem cells endothelial vascular regeneration and upregulation of genes coding for platelet and T lymphocyte activation, thus accelerating the atherosclerotic and atherothrombotic pathway.

Diabetes mellitus (DM) is a serious and growing global health challenge. The number of people diagnosed with diabetes continues to rise, and it is projected that by 2035 more than 592 million individuals worldwide will have diabetes [1]. DM can impact the heart through various mechanisms. Vascular complications are associated with diabetes and include both epicardial coronary artery and small vessel disease. Cardiomyopathy and heart failure may also occur. Insulin resistance causes cardiomyocytes to have a reduced capacity for glucose utilization, leading to increased uptake of free fatty acids. This, in turn, results in triglyceride storage and lipotoxicity, which contribute to impaired cardiac contractility [2].

Diabetes may lead to the production of advanced glycation end (AGE) products, resulting in an accumulation of reactive oxygen species. This accumulation triggers inflammation that can cause myocyte apoptosis and mitochondrial dysfunction. AGE can also contribute to cardiac fibrosis, which increases myocardial stiffness and results in heart failure with preserved ejection fraction (HFpEF) [2].

Background: One-third of patients with acute decompensated heart failure (ADHF) develop worsening kidney function, known as type I cardiorenal syndrome (CRS). CRS is linked to higher mortality rates, prolonged hospital stays, and increased readmissions.

Objectives: To explore the impact of real-time monitoring of urinary output (UO) trends on personalized pharmacologic management, fluid balance, and clinical outcomes of patients with ADHF admitted to a cardiac intensive care unit.

Methods: Our study comprised 35 patients who were hospitalized with ADHF and continuously monitored for UO (UO_elec). Standard diuretic and fluid protocols were implemented after 2 hours of oliguria, and patient outcomes were compared to a historical matched control (HMC) group. Patients were assessed for daily and cumulative fluid balance (over 72 hours) as well as for the occurrence of acute kidney injury (AKI).

Results: Significantly more patients in the UO_elec group demonstrated negative fluid balance daily and cumulatively over time in the intensive care unit compared to the HMC group: 91% vs. 20%, respectively (P < 0.0001 for 72-hour cumulative fluid balance). The incidence of AKI was significantly lower in the UO_elec monitoring cohort compared to the HMC: 23% vs. 57%, respectively (P = 0.003). Moreover, higher AKI resolution, and lower peak serum creatinine levels were demonstrated in the UO_elec group vs. the HMC group.

Conclusions: Implementing real-time monitoring of UO in ADHF patients allowed for early response to oliguria and goal-directed adjustment to treatment. This finding ultimately led to reduced congestion and contributed to early resolution of AKI.

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Background: Coronary heart disease (CHD) patients are considered high cardiovascular risks. Guidelines recommend low-density lipoprotein cholesterol (LDL-C) target levels below 55 mg/dl with > 50% reduction from baselines. These levels can be reached by a combination of statins, ezetimibe, and anti-protein convertase subtilisin/kexin type 9 (anti-PCSK9) agents. Our clinical impression was that CHD patients do not reach LDL-C target levels, despite the wide availability.

Objectives: To evaluate whether hospitalization would result in changes in lipid lowering regimens and short-term compliance.

Methods: We conducted a retrospective cohort study using data of CHD patients who were admitted to internal medicine wards at Clalit Health Services medical centers because of anginal syndrome during 2020–2022. The data were evaluated for demographic and clinical characteristics; LDL-C level at admission, 6 months previously, and 3 months and 6–9 months after discharge; rates of reaching LDL-C target levels; and lipid lowering treatment at admission, discharge, and 6–9 months after.

Results: The cohort included 10,540 patients. One-third and three-quarters did not have lipids level measurements up to 6 months before and during hospitalization, respectively. Only one-fifth of the patients reached LDL-C values before and during admission (median LDL-C 72 mg/dl; range 53–101). Approximately half were treated with high-dose potent statins. Only 10% were treated with ezetimibe. Hospitalization did not have a clinically significant effect on short-term lipid lowering treatment or LDL-C levels.

Conclusions: Gaps were noted between guidelines and clinical practice for reaching LDL-C target levels. Further education and strict policy are needed.

Background: Heart failure (HF) is an emerging pandemic associated with increased mortality, recurrent hospitalizations, and reduced quality of life. Guideline-directed medical therapy has been shown to improve outcomes, particularly in patients with HF with reduced ejection fraction (HFrEF). The main goal of HF clinics is optimizing medical therapy.

Objectives: To assess the impact of our HF clinic on medical therapy and clinical outcomes.

Methods: We obtained demographic, echocardiographic, and clinical data of patients listed in our HF clinic during a 4-year period. Medical therapy was evaluated based on patient reports and documented data. Recurrent admissions for HF were documented.

Results: A total of 317 patients (74.1% male, median age 66 years, IQR 55–74) were listed in the clinic with a total of 1140 visits. Of these patients, 62.5% had HFrEF, 20.5% presented with mildly reduced ejection fraction, and 17% showed preserved ejection fraction at the time of the first visit. The use of sodium glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists was optimized in 92% and 91% of the patients, respectively. In the subgroup of patients with HFrEF, the use of angiotensin-receptor antagonist/neprilysin inhibitor increased from 22.6% to 87.9% (P < 0.001) and SGLT2 inhibitor use increased from 49.2% to 92% (P < 0.001). During the follow-up period (2.2 years, IQR 1.1–3.1), 203 patients (64%) were readmitted to the hospital for HF at least once. The rate of readmissions decreased over time.

Conclusions: An HF clinic plays an important role in optimizing medical therapy and reducing readmissions.

Background: Left ventricular assist devices (LVAD) are a staple element in contemporary treatment of advanced heart failure. LVAD surgeries are mostly done in heart transplantations centers, as a destination therapy or as a bridge to heart transplantation.

Objectives: To describe our step-by-step experience in establishing and implementing a new LVAD program in a non-heart transplant center. To give insight to our short- and long-term results of our first 25 LVAD patients.

Methods: Preliminary steps included identifying the need for a new program and establishing the leading team. Next is defining protocols for pre-operative evaluation, operating room, post-operative management, and outpatient follow-up. The leading team needs to educate other relevant units in the hospital that will be involved in the care of these patients. It is essential to work in collaboration with a heart transplant center from the very beginning. Patient selection is of major importance especially in the early experience. Initially “low risk” patients should be enrolled.

Results: We describe our first 25 LVAD patients. Our first five patients all survived beyond 2 years, with no major complications. Overall, there was one operative death due to massive GI bleeding. There were four late deaths due to septic events.

Conclusions: Establishing a new LVAD program can be successful also with small- and medium-size programs. With careful and meticulous planning LVAD implantation can be extended to more centers thus offering an excellent solution for advanced heart failure patients.

Among patients admitted with acute decompensated heart failure (ADHF), deterioration of renal function with resulting acute kidney injury (AKI) is reported in up to 70% of patients with cardiogenic shock. Twenty percent of heart failure patients with AKI progress to dialysis (AKI-D). Optimal timing for initiation of renal replacement therapies (RRT) has been researched; however, minimal studies discuss guidelines for weaning from RRT [1]. Electronic monitoring of urine output (UO) may serve as a tool to aid in withdrawal from RRT. We present a case of ADHF with severe AKI requiring continuous renal replacement therapy (CRRT) where real-time electronic monitoring of UO was implemented for the first time to guide de-escalation therapy from CRRT until successful withdrawal.

Takotsubo syndrome (TTS) or Takotsubo cardiomyopathy (TCM) is a cardiomyopathy that develops rapidly and is usually caused by mental or physical stress. It is usually a transient cardiomyopathy. The presumed cause of the onset of the syndrome is the increase and extreme secretion of adrenaline and norepinephrine due to extreme stress. An infectious disease such as sepsis can also be the cause [1].

One of the most widespread diagnostic tools is the revised version of Mayo Clinic Diagnostic Criteria for TTS (2008) [2], which incorporates transient wall-motion abnormalities, absence of a potential coronary culprit, myocarditis, and pheochromocytoma. The prognosis for TTS is usually favorable and resolves with complete recovery in 4–8 weeks in more than 90% of patients.