Light-Chain (AL) Cardiac Amyloidosis Presenting as Heart Failure With Reduced Ejection Fraction.

Systemic amyloidosis is caused by the extracellular deposition of misfolded proteins in various organs and usually leads to organ dysfunction. The two common subtypes include light-chain amyloidosis and transthyretin amyloidosis. Deposition of these proteins in the heart can lead to infiltrative and restrictive cardiomyopathy, commonly manifesting as heart failure with preserved ejection fraction. However, systolic heart failure with reduced ejection fraction is mainly seen in the advanced stages of the disease. Here, we present the case of a 53-year-old female who presented with new-onset heart failure with reduced ejection fraction with no prior symptoms or diagnosis of amyloidosis and diastolic dysfunction.

Management of Pulmonary Hypertension in the Context of Heart Failure with Preserved Ejection Fraction.

PURPOSE OF REVIEW: To review the current evidence and modalities for treating pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF). RECENT FINDINGS: In recent years, several therapies have been developed that improve morbidity in HFpEF, though these studies have not specifically studied patients with PF-HFpEF. Multiple trials of therapies specifically targeting the pulmonary vasculature such as phosphodiesterase (PDE) inhibitors, prostacyclin analogs, endothelin receptor antagonists (ERA), and soluble guanylate cyclase stimulators have also been conducted. However, these therapies demonstrated lack of consistency in improving hemodynamics or functional outcomes in PH-HFpEF. There is limited evidence to support the use of pulmonary vasculature-targeting therapies in PH-HFpEF. The mainstay of therapy remains the treatment of the underlying HFpEF condition. There is emerging evidence that newer HF therapies such as sodium-glucose transporter 2 inhibitors and angiotensin-receptor-neprilysin inhibitors are associated with improved hemodynamics and quality of life of patients with PH-HFpEF. There is also a growing realization that more robust phenotyping PH and right ventricular (RV) function may hold promise for therapeutic strategies for patients with PH-HFpEF.

Association between nonalcoholic fatty liver disease and left ventricular diastolic dysfunction: A 7-year retrospective cohort study of 3,380 adults using serial echocardiography.

AIM: Left ventricular diastolic dysfunction (LVDD) has been observed in people with nonalcoholic fatty liver disease (NAFLD) in cross-sectional studies but the causal relationship is unclear. This study aimed to investigate the impact of NAFLD and the fibrotic progression of the disease on the development of LVDD, assessed by serial echocardiography, in a large population over a 7-year longitudinal setting. METHODS: This retrospective cohort study included the data of 3,380 subjects from a medical health check-up program. We defined subjects having NAFLD by abdominal ultrasonography and assessed significant liver fibrosis by the aspartate transaminase (AST) to platelet ratio index (APRI), the NAFLD fibrosis score (NFS), and the fibrosis-4 (FIB-4) index. LVDD was defined using serial echocardiography. A parametric Cox proportional hazards model was used. RESULTS: During 11,327 person-years of follow-up, there were 560 (16.0 %) incident cases of LVDD. After adjustment for multiple risk factors, subjects with NAFLD showed an increased adjusted hazard ratio (aHR) of 1.21 (95 % confidence interval [CI]=1.02-1.43) for incident LVDD compared to those without. The risk of LV diastolic dysfunction increased progressively with increasing degree of hepatic steatosis (P< 0.001). Compared to subjects without NAFLD, the multivariable-aHR (95 % CI) for LVDD in subjects with APRI < 0.5 and APRI ≥ 0.5 were 1.20 (1.01-1.42) and 1.36 (0.90-2.06), respectively (P= 0.036), while other fibrosis prediction models (NFS and FIB-4 index) showed insignificant results. CONCLUSIONS: This study demonstrated that NAFLD was associated with an increased risk of LVDD in a large cohort. More severe forms of hepatic steatosis and/or significant liver fibrosis may increase the risk of developing LVDD.

A classical case report of constrictive pericarditis, highlighting the role of magnetic resonance imaging and haemodynamic assessment.

Background: Constrictive pericarditis is a rare complication of pericarditis and is difficult to diagnose due to non-specific presentation. It mostly presents with right-sided heart failure as a consequence of a rigid pericardium that encases the heart causing impaired diastolic filling. Case summary: We present the case of a patient with signs and symptoms of dyspnoea and right-sided heart failure who was initially diagnosed with heart failure with preserved ejection fraction (HFpEF) but remained symptomatic despite being euvolaemic after treatment. A septal bounce and shudder on echocardiogram prompted further investigation. Eventually, cardiac magnetic resonance (CMR) imaging and invasive biventricular pressure measurements led to the diagnosis of constrictive pericarditis. A pericardiectomy was performed after which the patient was relieved of symptoms. Discussion: Constrictive pericarditis can mimic HFpEF. Due to its potentially curable character, timely recognition is of cardinal importance. In patients with symptoms of severe right-sided heart failure not resolving after diuretic therapy, a septal shudder on echocardiography should trigger further investigation, with e.g. CMR and cardiac catheterization.

Study the relationship between left atrial (LA) volume and left ventricular (LV) diastolic dysfunction and LV hypertrophy: Correlate LA volume with cardiovascular risk factors.

Heart failure (HF) with normal ejection fraction - the isolated diastolic heart failure, depicts increasing prevalence and health care burden in recent times. Having less mortality rate compared to systolic heart failure but high morbidity, it is evolving as a major cardiac concern. With increasing clinical use of Left atrial volume (LAV) quantitation in clinical settings, LAV has emerged as an important independent predictor of cardiovascular outcome in HF with normal ejection fraction. This article is intended to review the diastolic and systolic heart failure, their association with left atrial volume, in depth study of Left atrial function dynamics with determinants of various functional and structural changes.

Cardiac dysfunction rather than aortic valve stenosis severity drives exercise intolerance and adverse haemodynamics.

AIMS: To study the impact of heart failure with preserved ejection fraction (HFpEF) vs. aortic stenosis (AS) lesion severity on left ventricular (LV) hypertrophy, diastolic dysfunction, left atrial (LA) dysfunction, haemodynamics, and exercise capacity. METHODS AND RESULTS: Patients (n = 206) with at least moderate AS (aortic valve area ≤0.85 cm/m2) and discordant symptoms underwent cardiopulmonary exercise testing with simultaneous echocardiography. The population was stratified according to the probability of underlying HFpEF by the heavy, hypertension, atrial fibrillation, pulmonary hypertension, elder, filling pressure (H2FPEF) score [0-5 (AS/HFpEF-) vs. 6-9 points (AS/HFpEF+)] and AS severity (Moderate vs. Severe). Mean age was 73 ± 10 years with 40% women. Twenty-eight patients had Severe AS/HFpEF+ (14%), 111 Severe AS/HFpEF- (54%), 13 Moderate AS/HFpEF+ (6%), and 54 Moderate AS/HFpEF- (26%). AS/HFpEF+ vs. AS/HFpEF- patients, irrespective of AS severity, had a lower LV global longitudinal strain, impaired diastolic function, reduced LV compliance, and more pronounced LA dysfunction. The pulmonary arterial pressure-cardiac output slope was significantly higher in AS/HFpEF+ vs. AS/HFpEF- (5.4 ± 3.1 vs. 3.9 ± 2.2 mmHg/L/min, respectively; P = 0.003), mainly driven by impaired cardiac output and chronotropic reserve, with signs of right ventricular pulmonary arterial uncoupling. AS/HFpEF+ vs. AS/HFpEF- was associated with a lower peak aerobic capacity (11.5 ± 3.7 vs. 15.9 ± 5.9 mL/min/kg, respectively; P < 0.0001) but did not differ between Moderate and Severe AS (14.7 ± 5.5 vs. 15.2 ± 5.9 mL/min/kg, respectively; P = 0.6). CONCLUSION: A high H2FPEF score is associated with a reduced exercise capacity and adverse haemodynamics in patients with moderate to severe AS. Both exercise performance and haemodynamics correspond better with intrinsic cardiac dysfunction than AS severity.

Effect of different types of aerobic training on peak VO2 and ejection fraction for diastolic heart failure patients; a comparative randomized control trial.

BACKGROUND: Heart failure is described by a lack of confirmed efficient therapies and exercise intolerance. Engagement in physical activity decreases the possibility of adverse cardiovascular consequences involving heart failure. THE PURPOSE OF THE STUDY: Determine the effect of different types of aerobic training on peak VO2 and ejection fraction in diastolic heart failure patients. SUBJECT AND METHODS: The study was designed as a randomized control trail. Forty-eight eligible male patients with diastolic heart failure, aged between 50 and 65 years old, enrolled in this study. They were picked up from Police hospital outpatient clinic and were assigned to 2 equal groups in numbers. The first group (A) received aerobic exercise for the upper limb in the form of arm ergometer exercises, while the second group (B) received aerobic exercise for the lower limb in the form of cycling. Training duration for both groups was 3 sessions/week for 12 weeks. Peak VO2, and ejection fraction of both groups were measured and compared pre- and post-treatment. RESULTS: There was no significant difference (p > 0.05) in the ejection fraction between groups post-treatment. However, a significant increase (p < 0.001) was observed in the peak VO2 of group B when compared to group A post-treatment. CONCLUSION: There is no effect of different types of aerobic training on ejection fraction in diastolic heart failure patients, but lower limb exercise is more effective than upper limb exercise in improving peak VO2 in diastolic heart failure patients. Therefore, the current study recommended the use of lower limb exercise over upper limb exercise in training diastolic heart failure patients. CLINICAL TRIAL REGISTRATION: The study was registered in ClinicalTrial.gov as a clinical trial ID (NCT05637125).

Water Lung: An Interesting Case of Non-cardiogenic Pulmonary Edema in a Heart Failure Patient.

Contrast-induced pulmonary edema is a rare but life-threatening condition often missed in heart failure patients. We present a case of a 65-year-old female with a past medical history of coronary artery disease, diastolic heart failure, and chronic kidney disease who presented with chest pain. She received low osmolar intravenous (IV) contrast for cardiac catheterization. Within 24 hours of receiving the contrast, the patient developed respiratory distress, which was found to be secondary to pulmonary edema. Pulmonary edema was considered to be related to cardiogenic at first; however, the patient's physical examination was normal, with no jugular venous distention (JVD). A transthoracic echocardiogram showed a central venous pressure of 3 mmHg. The patient's respiratory condition improved after receiving an IV diuretic. Chart review showed that the patient had a similar presentation in the past, which was also thought to be related to heart failure leading to recurrent exposure to contrast. Non-cardiogenic pulmonary edema should be considered in the differential diagnosis of pulmonary edema in heart failure patients receiving contrast.

Heart of the Matter: Decoding the Underdiagnosed Cardiac Amyloidosis.

Cardiac amyloidosis, a rare disorder marked by toxic amyloid protein deposition in the myocardium, contributes significantly to restrictive cardiomyopathy. We present an 85-year-old female diagnosed with amyloid transthyretin (ATTR) cardiac amyloidosis, emphasizing the under-recognition of this condition. The pathophysiology of cardiac amyloidosis involves misfolded protein accumulation, which impairs myocardial function. Differentiating AL and ATTR is crucial, with ATTR predominance. Diagnosis relies on echocardiography, cardiac magnetic resonance, nuclear imaging, and biomarker testing. A positive pyrophosphate (PYP) scan, compatible echocardiographic features, and the absence of systemic myeloma signs diagnose ATTR amyloidosis. Management includes heart failure treatment, arrhythmia control, and disease-modifying strategies like Tafamidis, Inotersen, and Patisiran. Genotyping guides prognostic and therapeutic considerations. Recognizing cardiac amyloidosis as an underlying cause of heart failure with preserved ejection fraction necessitates collaboration between cardiology and hematology. Improved awareness, innovative diagnostics, and targeted therapies are crucial to reduce diagnostic delays and enhance outcomes.

Geranylgeranylacetone reduces cardiomyocyte stiffness and attenuates diastolic dysfunction in a rat model of cardiometabolic syndrome.

Titin-dependent stiffening of cardiomyocytes is a significant contributor to left ventricular (LV) diastolic dysfunction in heart failure with preserved LV ejection fraction (HFpEF). Small heat shock proteins (HSPs), such as HSPB5 and HSPB1, protect titin and administration of HSPB5 in vitro lowers cardiomyocyte stiffness in pressure-overload hypertrophy. In humans, oral treatment with geranylgeranylacetone (GGA) increases myocardial HSP expression, but the functional implications are unknown. Our objective was to investigate whether oral GGA treatment lowers cardiomyocyte stiffness and attenuates LV diastolic dysfunction in a rat model of the cardiometabolic syndrome. Twenty-one-week-old male lean (n = 10) and obese (n = 20) ZSF1 rats were studied, and obese rats were randomized to receive GGA (200 mg/kg/day) or vehicle by oral gavage for 4 weeks. Echocardiography and cardiac catheterization were performed before sacrifice at 25 weeks of age. Titin-based stiffness (Fpassive ) was determined by force measurements in relaxing solution with 100 nM [Ca2+ ] in permeabilized cardiomyocytes at sarcomere lengths (SL) ranging from 1.8 to 2.4 µm. In obese ZSF1 rats, GGA reduced isovolumic relaxation time of the LV without affecting blood pressure, EF or LV weight. In cardiomyocytes, GGA increased myofilament-bound HSPB5 and HSPB1 expression. Vehicle-treated obese rats exhibited higher cardiomyocyte stiffness at all SLs compared to lean rats, while GGA reduced stiffness at SL 2.0 µm. In obese ZSF1 rats, oral GGA treatment improves cardiomyocyte stiffness by increasing myofilament-bound HSPB1 and HSPB5. GGA could represent a potential novel therapy for the early stage of diastolic dysfunction in the cardiometabolic syndrome.

Sacubitril/Valsartan Cannot Improve Cardiac Function Compared with Valsartan in Patients Suffering Nonvalvular Atrial Fibrillation without Systolic Heart Failure.

This study investigates the effect of sacubitril/valsartan (Sac/Val) in patients diagnosed with nonvalvular atrial fibrillation (AF) without systolic heart failure (SHF).Nonvalvular AF patients without SHF admitted to the People's Hospital of Bortala Mongol Autonomous Prefecture from December 2020 to December 2021 were enrolled and randomly divided into Sac/Val treatment group (group T) and valsartan treatment group (group C, control). For subgroup analysis, patients were divided into subgroups with and without diastolic heart failure (DHF). After 1-month adaptive phase and subsequent 3-month treatment period, patients were followed up in the cardiology clinic. Plasma levels of biochemical markers and echocardiographic parameters before and after treatment were evaluated, and DHF scores were computed to assess diastolic function.Of 61 enrolled patients, 46 patients completed follow-up. Sac/Val treatment did not increase the percentage of sinus rhythm. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) expression tended to be reduced in both groups after 3 months of treatment, the differences compared with respective baseline levels and between groups were not significant. According to subgroup analysis, although NT-proBNP expression in the subgroup with DHF was lower at follow-up compared to baseline, the difference was not statistically significant. Similarly, no marked differences in echocardiographic parameters or tissue Doppler parameters related to DHF were detected between the groups (P > 0.05). Additionally, a subgroup analysis found no significant variations in the echocardiographic measures (P > 0.05).Sac/Val is not superior to valsartan for the short-term treatment of patients suffering with AF without SHF in improving NT-proBNP level and cardiac function.

A case report of constrictive pericarditis following COVID-19 vaccination.

Background: COVID-19 infection and the COVID-19 vaccines have been associated with rare cases of pericarditis. We present a case of constrictive pericarditis (CP) following the vaccine. Case summary: A 19-year-old healthy male started having progressive abdominal pain, emesis, dyspnoea, and pleuritic chest pain 2 weeks after the second dose of Pfizer vaccine. Computed tomography angiography chest revealed bilateral pleural effusions and pericardial thickening with effusion. Cardiac catheterization showed ventricular interdependence. Cardiac magnetic resonance (CMR) showed septal bounce and left ventricular tethering suggestive of CP. A total pericardiectomy was performed with significant symptom improvement. Pathology showed chronic fibrosis without amyloid, iron deposits, or opportunistic infections. Patient had Epstein-Barr Virus (EBV) viraemia 825 IU/mL and histoplasmosis complement-fixation positive with negative serum and urine antigen. Hypercoagulable panel and infectious workup were otherwise negative. The patient had resolution of cardiac symptoms at 3 months of follow-up. Discussion: The patient developed progressive symptoms within 2 weeks of his second Pfizer vaccine. Echocardiogram and CMR had classic signs of CP, and pericardial pathology confirmed fibrotic pericardium. The patient had no prior surgery, thoracic radiation, or bacterial infection. Epstein-Barr Virus viraemia was thought to be reactionary, and histoplasmosis complement likely represented chronic exposure. The timing of symptoms and negative multidisciplinary workup raises the suspicion for COVID vaccine-induced CP. The COVID vaccines benefits far exceed the risks, but complications still can occur. Practitioners should have a high index of suspicion to allow prompt diagnosis of CP.

Webtool to enhance the accuracy of diagnostic algorithms for HFpEF: a prospective cross-over study.

AIMS: Diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging. This study aimed to evaluate the potential of a webtool to enhance the scoring accuracy when applying the complex HFA-PEFF and H2 FPEF algorithms, which are commonly used for diagnosing HFpEF. METHODS AND RESULTS: We developed an online tool, the HFpEF calculator, that enables the automatic calculation of current HFpEF algorithms. We assessed the accuracy of manual vs. automatic scoring, defined as the percentage of correct scores, in a cohort of cardiologists with varying clinical experience. Cardiologists scored eight online clinical cases using a triple cross-over design (i.e. two manual-two automatic-two manual-two automatic). Data were analysed in study completers (n = 55, 29% heart failure specialists, 42% general cardiologists, and 29% cardiology residents). Manually calculated scores were correct in 50% (HFA-PEFF: 50% [50-75]; H2 FPEF: 50% [38-50]). Correct scoring improved to 100% using the HFpEF calculator (HFA-PEFF: 100% [88-100], P < 0.001; H2 FPEF: 100% [75-100], P < 0.001). Time spent on clinical cases was similar between scoring methods (±4 min). When corrections for faulty algorithm scores were displayed, cardiologists changed their diagnostic decision in up to 67% of cases. At least 67% of cardiologists preferred using the online tool for future cases in clinical practice. CONCLUSIONS: Manual calculation of HFpEF diagnostic algorithms is often inaccurate. Using an automated webtool to calculate HFpEF algorithms significantly improved correct scoring. This new approach may impact the eventual diagnostic decision in up to two-thirds of cases, supporting its routine use in clinical practice.

Pediatric heart failure with preserved ejection fraction, a review.

Diastolic dysfunction refers to a structural or functional abnormality of the left ventricle, resulting in impaired filling of the heart. Severe diastolic dysfunction can lead to congestive heart failure even when the left ventricle systolic function is normal. Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of the hospitalizations for acute heart failure in the adult population but the clinical recognition and understanding of HFpEF in children is poor. The condition is certainly much less frequent than in the adult population but the confirmatory diagnosis of diastolic dysfunction in children is also challenging. The underlying causes of HFpEF in children are diverse and differ from the main cause in adults. This review addresses the underlying causes and prognostic factors of HFpEF in children. We describe the pulmonary hypertension profiles associated with this cardiac condition. We discuss diagnosis difficulties in clinical practice, and we provide a simplified diagnostic algorithm for HFpEF in children.

Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross-over trial.

AIMS: Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. METHODS AND RESULTS: The DoPING-HFpEF trial was a phase II single-centre, double-blind, placebo-controlled, randomized cross-over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2-week wash-out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2 ); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI -2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6-min walking distance (mean change of -6 [95% CI -18, 7] m vs. -5 [95% CI -22, 22] m, respectively, P = 0.93), N-terminal pro-B-type natriuretic peptide (5 (-156, 166) ng/L vs. -13 (-172, 147) ng/L, P = 0.70), overall quality-of-life (KCCQ and EQ-5D-5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. CONCLUSIONS: Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF.

Paradoxical Left Ventricular Hypertrophy by Echocardiogram and Low Voltage ECG: A Key Clue in the Diagnostic Workup of Two Distinct Presentations of Cardiac AL Amyloidosis.

Cardiac amyloidosis remains a rare disease caused by the extracellular deposition of abnormal proteins-amyloids in the myocardium. These protein structures in the myocardium are associated with high morbidity and mortality, with prognosis hinging on early detection and treatment. Three main types of cardiac amyloidosis have been identified: light chain (AL), familial or senile (ATTR), and secondary amyloidosis which is associated with chronic inflammation. Cardiac amyloidosis classically presents as diastolic heart failure with symptoms of volume overload low voltage on electrocardiogram (ECG) and echocardiographic features of diastolic dysfunction and paradoxical left ventricular hypertrophy (paradoxical with respect to low voltage on ECG). Early suspicion should trigger additional laboratory and imaging workup to facilitate early detection. Early detection remains critical to prognosis. Herein, we present two patients admitted to a safety-net hospital within one month of each other with distinct presentations yet important, overlapping characteristics that led to the diagnosis of AL amyloidosis in both patients.

Heart failure with preserved ejection fraction: relevance of a dedicated dyspnoea clinic.

BACKGROUND AND AIMS: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous presentation. This study provides an in-;depth description of haemodynamic and metabolic alterations revealed by systematic assessment through cardiopulmonary exercise testing combined with exercise echocardiography (CPETecho) within a dedicated dyspnoea clinic. METHODS AND RESULTS: Consecutive patients (n = 297), referred to a dedicated dyspnoea clinic using a standardized workup including CPETecho, with HFpEF diagnosed through a H2FPEF score ≥6 or HFA-PEFF score ≥5, were evaluated. A median of four haemodynamic/metabolic alterations was uncovered per patient: impaired stroke volume reserve (73%), impaired chronotropic reserve (72%), exercise pulmonary hypertension (65%), and impaired diastolic reserve (64%) were the most frequent cardiac alterations. Impaired peripheral oxygen extraction and a ventilatory limitation were present in 40% and 39%, respectively. In 267 patients (90%), 575 further diagnostic examinations were recommended (median of two tests per patient). Cardiac magnetic resonance imaging, coronary or amyloidosis workup, ventilation-perfusion scanning, and pulmonology referral were each recommended in approximately one out of three patients. In 293 patients (99%), 929 cardiovascular drug optimizations were performed (median of 3 modifications per patient). In 110 patients (37%), 132 cardiovascular interventions were performed, with ablation as the most frequent procedure. CONCLUSION: Holistic workup of HFpEF patients within a multidisciplinary, dedicated dyspnoea clinic, including systematic implementation of CPETecho reveals various haemodynamic/metabolic alterations, leading to further diagnostic testing and potential treatment changes in the majority of cases.

The Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Improving Morbidity and Mortality of Heart Failure: A Systematic Review.

Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 2 diabetes mellitus (DM) worldwide. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed for treating patients with type 2 DM. The four major drugs developed are canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. Apart from treating DM, these drugs have shown to have a beneficial effect on lowering cardiovascular death and lowering hospital admission, and have beneficial renal outcomes. Recently, several large-scale randomized controlled trials (RCTs) were done to assess the benefit of these drugs, mainly in patients with CVD, irrespective of their diabetic status. This systematic review examined seven large-scale randomized controlled trials that focused mainly on CVD in patients with type 2 DM and if it showed any improvement. We properly screened the RCTs if they demonstrated cardiovascular outcomes after taking the SGLT2i or a placebo drug. The seven studies combined had a total sample population of 55,433, and the mean follow-up time was about four years. The participants included in this study had various basal metabolic indices, ages, glomerular filtration rates, and diabetic status characteristics. Although these patients were quite different, after the administration of SGLT2i, the studies showed a beneficial effect in reducing CVD mortality and morbidity in patients with type 2 DM.