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Journal of the American Heart... Jun 2024The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal...
BACKGROUND
The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes.
METHODS AND RESULTS
We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD-related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short-term finerenone treatment decreased LV end-diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity.
CONCLUSIONS
We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.
Topics: Animals; Mineralocorticoid Receptor Antagonists; Renal Insufficiency, Chronic; Naphthyridines; Ventricular Dysfunction, Left; Male; Disease Models, Animal; Fibrosis; Nitric Oxide Synthase Type III; Glomerular Filtration Rate; Ventricular Function, Left; Diastole; Kidney; Phosphorylation; Myocardium; Rats, Sprague-Dawley; Rats; Nephrectomy
PubMed: 38842271
DOI: 10.1161/JAHA.123.032971 -
Clinical Liver Disease 2024
Review
PubMed: 38841197
DOI: 10.1097/CLD.0000000000000090 -
Clinical profiling of patients admitted with acute heart failure: a comprehensive survival analysis.Frontiers in Cardiovascular Medicine 2024In heart failure (HF), not all episodes of decompensation are alike. The study aimed to characterize the clinical groups of decompensation and perform a survival...
BACKGROUND
In heart failure (HF), not all episodes of decompensation are alike. The study aimed to characterize the clinical groups of decompensation and perform a survival analysis.
METHODS
A retrospective study was conducted on patients consecutively admitted for HF from 2018 to 2023. Patients who died during admission were excluded (final number 1,668). Four clinical types of HF were defined: low cardiac output (:83), pulmonary congestion (:1,044), mixed congestion (:353), and systemic congestion (:188).
RESULTS
The low output group showed a higher prevalence of reduced left ventricular ejection fraction (93%) and increased biventricular diameters ( < 0.01). The systemic congestion group exhibited a greater presence of tricuspid regurgitation with dilatation and right ventricular dysfunction (:0.0001), worse renal function, and higher uric acid and CA125 levels (:0.0001). Diuretics were more commonly used in the mixed and, especially, systemic congestion groups (:0.0001). The probability of overall survival at 5 years was 49%, with higher survival in pulmonary congestion and lower in systemic congestion (:0.002). Differences were also found in survival at 1 month and 1 year (:0.0001).
CONCLUSIONS
Mortality in acute HF is high. Four phenotypic profiles of decompensation differ clinically, with distinct characteristics and varying prognosis in the short, medium, and long term.
PubMed: 38836065
DOI: 10.3389/fcvm.2024.1381514 -
Frontiers in Cardiovascular Medicine 2024Neonatal (enteroviral) myocarditis (NM/NEM) is rare but unpredictable and devastating, with high mortality and morbidity. We report a case of neonatal coxsackievirus B...
BACKGROUND
Neonatal (enteroviral) myocarditis (NM/NEM) is rare but unpredictable and devastating, with high mortality and morbidity. We report a case of neonatal coxsackievirus B (CVB) fulminant myocarditis successfully treated with veno-arterial extracorporeal membrane oxygenation (V-A ECMO).
CASE PRESENTATION
A previously healthy 7-day-old boy presented with fever for 4 days. Progressive cardiac dysfunction (weak heart sounds, hepatomegaly, pulmonary edema, ascites, and oliguria), decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS), transient ventricular fibrillation, dramatically elevated creatine kinase-MB (405.8 U/L), cardiac troponin I (25.85 ng/ml), and N-terminal pro-brain natriuretic peptide (NT-proBNP > 35,000 ng/L), and positive blood CVB ribonucleic acid indicated neonatal CVB fulminating myocarditis. It was refractory to mechanical ventilation, fluid resuscitation, inotropes, corticosteroids, intravenous immunoglobulin, and diuretics during the first 4 days of hospitalization (DOH 1-4). The deterioration was suppressed by V-A ECMO in the next 5 days (DOH 5-9), despite the occurrence of bilateral grade III intraventricular hemorrhage on DOH 7. Within the first 4 days after ECMO decannulation (DOH 10-13), he continued to improve with withdrawal of mechanical ventilation, LVEF > 60%, and FS > 30%. In the subsequent 4 days (DOH 14-17), his LVEF and FS decreased to 52% and 25%, and further dropped to 37%-38% and 17% over the next 2 days (DOH 18-19), respectively. There was no other deterioration except for cardiomegaly and paroxysmal tachypnea. Through strengthening fluid restriction and diuresis, and improving cardiopulmonary function, he restabilized. Finally, notwithstanding NT-proBNP elevation (>35,000 ng/L), cardiomegaly, and low LVEF (40%-44%) and FS (18%-21%) levels, he was discharged on DOH 26 with oral medications discontinued within 3 weeks postdischarge. In nearly three years of follow-up, he was uneventful, with interventricular septum hyperechogenic foci and mild mitral/tricuspid regurgitation.
CONCLUSIONS
Dynamic cardiac function monitoring via real-time echocardiography is useful for the diagnosis and treatment of NM/NEM. As a lifesaving therapy, ECMO may improve the survival rate of patients with NM/NEM. However, the "honeymoon period" after ECMO may cause the illusion of recovery. Regardless of whether the survivors of NM/NEM have undergone ECMO, close long-term follow-up is paramount to the prompt identification and intervention of abnormalities.
PubMed: 38836060
DOI: 10.3389/fcvm.2024.1364289 -
Federal Practitioner : For the Health... Feb 2024Regardless of age, first-line therapy for uncomplicated hypertension includes thiazide diuretics, long-acting calcium channel blockers, and renin-angiotensin system...
BACKGROUND
Regardless of age, first-line therapy for uncomplicated hypertension includes thiazide diuretics, long-acting calcium channel blockers, and renin-angiotensin system inhibitors. Even though older adults are often at increased risk of adverse drug events, specific guidelines for choosing between different classes of antihypertensives are lacking. Given the prevalence of hypertension in older adults, clinicians should be aware of the increased risk of electrolyte disorders after the initiation of thiazide diuretics in this population.
CASE PRESENTATION
A patient aged > 90 years fell getting out of his bed 2 weeks following initiation of hydrochlorothiazide 25 mg daily medication therapy. Laboratory tests revealed a urine sodium of 35 mmol/L most consistent with hypovolemic hypoosmotic hyponatremia secondary to thiazide initiation. Hydrochlorothiazide was discontinued and sodium gradually normalized over the next 2 weeks without any other intervention.
CONCLUSIONS
Despite being recommended as first-line therapy for uncomplicated hypertension, thiazide diuretics may cause more harm than good in older adults with risk factors for thiazide-induced hyponatremia, which should be considered before initiation.
PubMed: 38835924
DOI: 10.12788/fp.0443 -
American Journal of Medicine Open Jun 2023Patients admitted with pneumonia and heart failure (HF) have increased mortality and cost compared to those without HF, but it is not known whether outcomes differ...
BACKGROUND
Patients admitted with pneumonia and heart failure (HF) have increased mortality and cost compared to those without HF, but it is not known whether outcomes differ between systolic and diastolic HF. Management of concomitant pneumonia and HF is complicated because HF treatments can worsen complications of pneumonia.
METHODS
This is a retrospective cohort study from the Premier Database among patients admitted with pneumonia between 2010-2015. Patients were categorized based on systolic, diastolic, and combined HF using ICD-9 codes. The primary outcome was in-hospital mortality. Secondary outcomes included use of HF medications, length of stay, cost, intensive care unit (ICU) admission, as well as use of invasive mechanical ventilation (IMV), vasopressors and inotropes. Multivariable logistic regression was used to describe associations of these outcomes with type of HF.
RESULTS
Of 123,211 patients with pneumonia and HF, 41,196 (33.4%) had systolic HF, 69,982 (56.8%) diastolic HF, and 12,033 (9.8%) had combined HF. Compared to patients with diastolic HF, after multivariable adjustment systolic HF was associated with higher in-hospital mortality (OR 1.15; 95% CI:1.11-1.20), ICU admission, and use of IMV and vasoactive agents, but not with increased length of stay or cost. Among patients with systolic HF, 80% received a loop diuretic, 72% a beta blocker, 48% angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and 12.5% a mineralocorticoid receptor antagonist.
CONCLUSION
Systolic HF is associated with added risk in pneumonia compared to diastolic HF. There may also be an opportunity to optimize medications in systolic HF prior to discharge.
PubMed: 38835731
DOI: 10.1016/j.ajmo.2022.100025 -
Journal of the Saudi Heart Association 2024Worsening renal function is a frequent finding in patients with acute decompensated heart failure (ADHF) and is a powerful independent prognostic factor for adverse...
BACKGROUND
Worsening renal function is a frequent finding in patients with acute decompensated heart failure (ADHF) and is a powerful independent prognostic factor for adverse outcomes. The link between abdominal congestion and worsening renal function in such patients is not yet fully addressed.
OBJECTIVE
To evaluate the role of abdominal congestion in the early prediction of worsening renal function in hospitalized patients with acute decompensated heart failure.
METHODS
This was a prospective study that enrolled 100 patients with a diagnosis of ADHF and received intravenous diuretic therapy. Intra-abdominal pressure (IAP), splenic Doppler impedance indices and serum prouroguanylin were measured on admission, 24 h after admission and on discharge. Patients were then divided into 2 groups: those who developed WRF (WRF group), and those who did not (non-WRF group). Worsening renal function was defined as an increase in serum creatinine level ≥0.3 mg/dL above baseline admission value. Intrabdominal pressure was measured transvesically using standard Foley catheter. Splenic Doppler impedance indices (resistivity and pulsatility indices) were measured using splenic Doppler ultrasound.
RESULTS
Among recruited patients (age: 54.73 ± 13.1 years, 72% are male), there was a significant decline in IAP (6.67 mmHg vs 8.36 mmHg, p = 0.001) and significant rise in splenic resistivity index (0.69 vs 0.67, p = 0.002) before discharge compared to admission values. The median level of serum prouroguanylin before discharge showed significant decline compared to admission level (29.2 vs 34.6 ng/l, p = 0.006). WRF developed in 37 (37%) patients. Independent predictors of WRF during hospitalization were high splenic arterial resistivity index 24 h after admission, high intra-abdominal pressure (≥8 mmHg) 24 h after admission, and low LVEF on admission.
CONCLUSION
In ADHF patients receiving diuretic therapy, transvesical measurement of intra-abdominal pressure and splenic resistivity index by splenic Doppler early after admission can help to identify patients at increased risk of WRF near discharge.
PubMed: 38832351
DOI: 10.37616/2212-5043.1371 -
Frontiers in Cardiovascular Medicine 2024Acute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium-glucose cotransporter-2...
BACKGROUND
Acute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium-glucose cotransporter-2 (SGLT2) inhibitors post-ACS in patients with acute HF (AHF) and diabetes.
METHODS
We conducted a retrospective observational cohort study employing propensity score matching. This study involved patients with diabetes admitted with ACS complicated by AHF, defined as either new clinical HF requiring diuretics during the index admission or having an ejection fraction (EF) of <40%. The study population was divided into two groups; (1) SGLT2 inhibitor users and (2) SGLT2 inhibitor non-users. The Cox proportional hazard regression analysis was used to evaluate the outcomes.
RESULTS
A total of 465 patients (93% male; mean age, 55 ± 10 years) were included in this study. Using a 1 : 1 propensity score matching, 78 patients were included per arm with an absolute standardized difference of <0.1 for all baseline characteristics. The use of SGLT2 inhibitors resulted in lower composite outcomes of ACS, HF hospitalization, and all-cause mortality at 1 month and 12 months [1 month: 2.6% vs. 11.5%, HR = 0.20 (0.04-0.94), = 0.041; 12 months: 14.1% vs. 23.1%, HR = 0.46 (0.22-0.99), = 0.046].
CONCLUSION
The findings suggest that SGLT2 inhibitors may confer cardioprotective effects in ACS-induced AHF, thereby widening the spectrum for indications of SGLT2 inhibitors.
PubMed: 38832317
DOI: 10.3389/fcvm.2024.1383669 -
Chest Jun 2024Acute pulmonary embolism (PE) is a common disease encountered by pulmonologists, cardiologists, and critical care physicians throughout the world. For patients with... (Review)
Review
TOPIC IMPORTANCE
Acute pulmonary embolism (PE) is a common disease encountered by pulmonologists, cardiologists, and critical care physicians throughout the world. For patients with high-risk acute PE (defined by systemic hypotension) and intermediate high-risk acute PE (defined by the absence of systemic hypotension, but the presence of numerous other concerning clinical and imaging features), intensive care often is necessary. Initial management strategies should focus on optimization of right ventricle (RV) function while decisions about advanced interventions are being considered.
REVIEW FINDINGS
We reviewed the existing literature of various vasoactive agents, IV fluids and diuretics, and pulmonary vasodilators in both animal models and human trials of acute PE. We also reviewed the potential complications of endotracheal intubation and positive pressure ventilation in acute PE. Finally, we reviewed the data of venoarterial extracorporeal membrane oxygenation (ECMO) use in acute PE. The above interventions are discussed in the context of the underlying pathophysiologic features of acute RV failure in acute PE with corresponding illustrations.
SUMMARY
Norepinephrine is a reasonable first choice for hemodynamic support with vasopressin as an adjunct. IV loop diuretics may be useful if evidence of RV dysfunction or volume overload is present. Fluids should be given only if concern exists for hypovolemia and absence of RV dilatation. Supplemental oxygen administration should be considered even without hypoxemia. Positive pressure ventilation should be avoided if possible. venoarterial ECMO cannulation should be implemented early if ongoing deterioration occurs despite these interventions.
PubMed: 38830402
DOI: 10.1016/j.chest.2024.04.032 -
Journal of Cardiovascular Pharmacology... 2024Moxonidine, an imidazoline I receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
MARRIAGE: A Randomized Trial of Moxonidine Ramipril or in Combination With Ramipril in Overweight Patients With Hypertension and Impaired Fasting Glucose or Diabetes Mellitus. Impact on Blood Pressure, Heart Rate and Metabolic Parameters.
BACKGROUND
Moxonidine, an imidazoline I receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic.
AIMS
This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes.
METHODS
Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment.
RESULTS
Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters.
CONCLUSION
Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.
Topics: Humans; Ramipril; Hypertension; Male; Middle Aged; Female; Blood Pressure; Heart Rate; Double-Blind Method; Imidazoles; Antihypertensive Agents; Blood Glucose; Overweight; Drug Therapy, Combination; Diabetes Mellitus, Type 2; Aged; Adult; Treatment Outcome; Angiotensin-Converting Enzyme Inhibitors
PubMed: 38828542
DOI: 10.1177/10742484241258381