Background: No previous studies have evaluated the effect of an aspirin-free strategy for patients undergoing staged percutaneous coronary intervention (PCI).

Methods and Results: We conducted a post hoc subgroup analysis in patients undergoing staged PCI within 1 month in STOPDAPT-3 (n=6,002), which randomly compared prasugrel monotherapy with dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome or high bleeding risk. The co-primary endpoints were major bleeding (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month. There were 814 patients undergoing staged PCI within 1 month (no-aspirin group, n=401; DAPT group, n=413). The median interval from randomization to the first staged PCI was 8 (interquartile range 5–13) days. More than 90% of the patients received assigned antiplatelet agents at all staged PCI procedures. The effect of no-aspirin relative to DAPT was not different for the co-primary bleeding (3.74% vs. 1.94%; HR 1.94; 95% CI 0.82–4.57) and cardiovascular (3.49% vs. 2.42%; HR 1.44; 95% CI 0.64–3.25) endpoints. The no-aspirin group compared with the DAPT group had a numerically higher incidence of the co-primary cardiovascular endpoint, which occurred after the first staged PCI procedure (2.49% vs. 1.21%; HR 2.07; 95% CI 0.71–6.05).

Conclusions: An aspirin-free prasugrel monotherapy relative to DAPT had numerically higher risks of cardiovascular and major bleeding events in patients undergoing staged PCI at 1 month.

Background: The cardio-ankle vascular index (CAVI) is an important marker of arterial stiffness, providing a blood pressure-independent assessment of vascular function. However, the clinical significance of low CAVI values remains unclear. Some connective tissue diseases are associated with aortic diseases due to intrinsic arterial wall abnormalities and may exhibit low CAVI values. This study aimed to investigate whether low CAVI is associated with these connective tissue diseases and succeeding aortic diseases.

Methods and Results: This was a single-center, retrospective observational study conducted at Juntendo University Hospital. A total of 17,364 patients aged 20–80 years who underwent arterial stiffness analysis using CAVI were included. Low CAVI was defined as the lowest 2.5 percentile within each sex- and age-specific distribution. The prevalences of aortic diseases (dissection and/or aneurysm) and Marfan syndrome were similar between the between the low CAVI and normal CAVI groups (aortic disease, 3.99% vs. 3.99%, P>0.99; Marfan syndrome, 0.04% vs. 0.07%, P>0.99, for the low and normal CAVI group, respectively).

Conclusions: This study found no evidence that patients with low CAVI had an increased prevalence of aortic dissection, aortic aneurysm, or Marfan syndrome. Further studies are needed to clarify the clinical implications of low CAVI in vascular diseases.

Background: Data on cardiac rehabilitation (CR) outcomes in patients with cardiovascular disease (CVD), frailty, and multimorbidity in post-acute settings are limited. This study aimed to evaluate the feasibility and efficacy of individualized, multidisciplinary CR in convalescent rehabilitation hospitals (cRHs).

Methods and Results: This multicenter, prospective, observational study included 72 consecutive patients transferred from acute care hospitals. Personalized CR programs were implemented in cRHs. Primary outcomes were changes in the Barthel Index (BI) and functional independence measure (FIM) scores. Secondary outcomes included assessments of physical and cognitive function, and nutritional status. Mean participant age was 78.6±11.8 years. Prior to admission, 51.4% experienced acute decompensated heart failure (ADHF). The average length of stay was 59.5±39.2 days. BI and FIM scores improved from admission to discharge. The following parameters improved: Short Physical Performance Battery, knee extensor strength, comfortable gait speed, 6-min walk distance, New York Heart Association classification, and cognitive function (Mini-Mental State Examination). Discharge dispositions included 53 (73.6%) home discharges, and 19 (26.4%) outpatient CR post-discharges. Patients with post-ADHF and patients with other conditions both showed functional improvements, but ∆BI and ∆FIM were lower in the post-ADHF group.

Conclusions: Tailored multidisciplinary CR in cRHs effectively improves daily living activities and physical and cognitive outcomes in patients with CVD with complex conditions. Expanded use of these hospitals may help address clinical challenges.

Background: Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values after initiating sacubitril/valsartan (Sac/Val) are considered a favorable prognostic factor in patients with heart failure (HF). However the relationship between the trajectory of repeated NT-proBNP measurements and cardiovascular events after Sac/Val remains uncertain.

Methods and Results: A Japanese nationwide multicenter study enrolled 995 patients who were prescribed Sac/Val from August 2020 to August 2021. Of them, 434 patients who had a complete set of NT-proBNP measurements were divided into 3 groups: sustained-responder group (n=129), with ≥10% reduction in NT-proBNP at 1 month and further ≥10% reduction at 3 months; transient-responder group (n=161), with ≥10% reduction at 1 month but not at 3 months; and non-responder group (n=144), without ≥10% reduction at 1 month. There were no significant differences in the mean Sac/Val dose at each measurement point among the 3 groups. During a median follow-up of 456 (interquartile range: 371–549) days, the primary endpoint, which was either cardiovascular death or hospitalization for HF, occurred in 78 patients. Kaplan-Meier analysis revealed that the sustained-responder group had a significantly higher event-free survival rate among the 3 groups (Log-rank P<0.001).

Conclusions: Repeated NT-proBNP monitoring and the pattern of the NT-proBNP trajectory after Sac/Val may be helpful in optimizing HF therapy and understanding the prognosis of HF.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a major cause of heart failure in elderly patients with left ventricular hypertrophy. Although tafamidis was approved in 2019 following the ATTR-ACT study, its real-world survival impact in community settings remains unclear.

Methods and Results: This retrospective study analyzed 117 patients diagnosed with ATTR-CM at a single center from 2015 to 2024, with 75 receiving tafamidis and 42 untreated. Among the 83 patients who underwent genetic testing, all had the wild-type genotype. ATTR-CM diagnoses increased significantly after the advent of ^{99 m}Tc-pyrophosphate scintigraphy and tafamidis. Kaplan-Meier analysis showed significantly longer survival in tafamidis-treated patients. Multivariate analysis identified New York Heart Association (NYHA) functional class, left ventricular wall thickness, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, and tafamidis treatment as independent survival predictors. Tafamidis treatment was associated with significantly improved survival in patients who were younger, had a less advanced NYHA functional class, and lower levels of NT-proBNP and troponin T. In contrast, its survival benefits were marginal in patients with older age, higher NYHA functional class, elevated NT-proBNP levels, and increased troponin T levels.

Conclusions: In this real-world cohort, tafamidis treatment was significantly associated with better survival in ATTR-CM patients, particularly when initiated in the early stage. Therefore, early detection and timely initiation of treatment are critical for optimizing clinical outcomes in this increasingly recognized condition.

Background: The precise pathogenesis of Kawasaki disease (KD) remains unclear, but immune dysregulation involving damage-associated molecular patterns (DAMPs), such as oxidized low-density lipoprotein (LDL) and high mobility group box 1 (HMGB1), has been implicated. We investigated the roles of 2 anti-DAMPs antibodies in KD and their associations with inflammatory and oxidative stress markers.

Methods and Results: Serum levels of anti-oxidized LDL and anti-HMGB1 antibodies were measured by enzyme-linked immunosorbent assay in patients with KD and in febrile disease controls (DC). Correlations with inflammatory (C-reactive protein [CRP]) and oxidative stress (red blood cell distribution width [RDW]) markers were evaluated. Serum anti-oxidized LDL antibody levels increased significantly after intravenous immunoglobulin (IVIG) therapy in KD patients, suggesting a protective role of anti-oxidized LDL antibodies against vascular inflammation. Conversely, anti-HMGB1 antibody levels showed a decreasing trend post-IVIG. A significant correlation between antibody levels and CRP was observed in DC but not in KD patients. Furthermore, a weak inverse trend between anti-oxidized LDL antibodies and RDW-coefficient of variation was noted in KD patients.

Conclusions: This study highlighted the distinct roles of anti-oxidized LDL and anti-HMGB1 antibodies during the acute phase of KD. The increase in anti-oxidized LDL antibodies following IVIG treatment suggests a protective effect, while the transient nature of anti-HMGB1 antibodies warrants further exploration.

Background: Chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in patients with chronic heart failure (CHF). A growing number of patients are suffering from both COPD and CHF, and these conditions worsen each other. Inhaled bronchodilator therapy with long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) in combination is currently the mainstay of treatment for COPD. However, the effect of LAMA/LABA on HF with COPD remains unknown.

Methods and Results: The COPD-HF trial is a multicenter, double-arm, open-label, exploratory, investigator-initiated clinical study to investigate the effect of LAMA/LABA on HF in patients suffering from both COPD and CHF. The participants are randomly assigned (1 : 1) to the LAMA/LABA (tiotropium+olodaterol FDC (fixed-dose combination) 5/5 ug) group (once a day, 2 inhalations) or non-pharmacological treatments for COPD as a control group. The planned number of patients to be enrolled in this trial is 54 in total (27 in each group). The participants are followed up for 12 weeks with and without LAMA/LABA. The primary endpoint is the change in plasma B-type natriuretic peptide levels from the baseline to the end of this study (12 weeks).

Conclusions: The COPD-HF trial will investigate the efficacy of LAMA/LABA on HF in patients with COPD and CHF.

Background: Dapagliflozin is clinically beneficial in heart failure (HF). However, how these clinical benefits translate into economic burden reduction is unclear. With IMPLICATION HF, we projected the reductions in HF events and costs that would result from dapagliflozin use in Japan using a cost offset model.

Methods and Results: The modeled population comprised symptomatic HF patients from the DAPA-HF and DELIVER trials. We compared the event incidences and associated costs between HF treatment with and without dapagliflozin, using the prevalence, event rates, and event costs of HF in Japan from published literature, as well as the treatment effects of dapagliflozin from the pooled meta-analysis of DAPA-HF and DELIVER. The cumulative number of events (HF hospitalization [hHF], cardiovascular [CV] death, and all-cause death) and associated costs (hHF, CV death, total) were projected. Cost offsets were calculated according to the difference in event-related costs between HF treatment with and without dapagliflozin. Dapagliflozin was estimated to prevent 63,770 hHF events (number needed to treat [NNT] 20), 11,613 CV deaths (NNT 108), and 16,141 all-cause deaths (NNT 78), as well as reducing hHF and CV death costs by JPY62.7 billion and JPY16.6 billion, totaling JPY79.3 billion over 1 year in Japan. The sensitivity analyses corroborated these findings.

Conclusions: The addition of dapagliflozin to HF treatment is projected to provide economic benefits to the Japanese healthcare system.

Background: This study aimed to optimize the fusion of quantitative maps and morphological images to improve late iodine enhancement (LIE) imaging using cardiac dual-energy computed tomography (DECT).

Methods and Results: We retrospectively analyzed 15 patients with suspected old myocardial infarction who underwent cardiac DECT. Virtual monochromatic images (VMI) ranging from 40 to 200 keV and quantitative maps (e.g., iodine concentration, effective atomic number, and electron density [(%EDW: percentage relative to the electron density of water)] were generated. The contrast-to-noise ratio (CNR) between LIE areas and the left ventricular (LV) blood pool and normal myocardium was calculated to determine the optimal image fusion for LIE delineation. VMI at 40 keV demonstrated superior CNR between LIE areas and normal myocardium. Electron density was significantly higher in LIE areas [105.5%EDW (interquartile range (IQR): 105.15–105.65)] than in the LV blood pool [104.4%EDW (IQR: 104.3–104.6)] and normal myocardium [104.4%EDW (IQR: 104.2–104.65)] (P<0.001). Iodine concentration and effective atomic number differed significantly between LIE areas and normal myocardium, but did not differ significantly between LIE areas and the LV blood pool. Fusion of 40 keV VMI with electron density maps yielded the highest area under the receiver operating characteristic curve (0.917).

Conclusions: Fused images combining 40 keV VMI with electron density maps significantly enhanced the visualization of LIE areas on DECT, offering improved contrast and diagnostic accuracy for the assessment of myocardial territories.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is a potential treatment for cardiovascular disease, but data on its effects on physiological function during exercise are lacking. We investigated the effects of taVNS on hemodynamics and autonomic nervous system function during exercise stress tests.

Methods and Results: Sixteen healthy volunteers underwent exercise stress tests with and without taVNS in this study, with a randomized crossover design and with a washout period of at least 7 days. taVNS was set to a frequency of 100 Hz and maximum current intensity without causing discomfort. Hemodynamics and autonomic nervous system function were evaluated using plethysmography and heart rate (HR) variability, respectively. After exclusion of an outlier, data of 15 participants were analyzed. In tests with taVNS, HR was significantly reduced at maximum exercise (136.0±9.7 vs. 132.0±9.2; P<0.001) and 1 min after exercise (115.0±11.4 vs. 104.0±15.0; P<0.001), with minimal changes in blood pressure. The stroke volume and total peripheral resistance at maximum exercise significantly increased and decreased, respectively. Furthermore, low/high frequency ratio reflecting sympathetic dominance decreased at rest (3.7±2.5 vs. 1.6±1.3; P<0.001) and at maximum exercise (4.5±4.5 vs. 1.2±0.9; P<0.001).

Conclusions: taVNS can reduce HR with minimal effect on blood pressure by inducing parasympathetic dominance during exercise stress tests.

Background: Persistent left ventricular hypertrophy (LVH) after surgical aortic valve replacement (SAVR) for aortic stenosis (AS) worsens prognosis. We investigated predictors of LVH regression 1 year after SAVR in AS patients, including patient-prosthesis mismatch (PPM) and valvuloarterial impedance (Zva).

Methods and Results: We retrospectively studied 175 patients who underwent SAVR for AS at Jichi Medical University between 2014 and 2019. Echocardiography was performed at preoperative baseline, 1-week postoperative, and 1-year postoperative. The left ventricular mass index (LVMI) regression rate (RR) was defined as the difference between baseline LVMI and 1-year LVMI divided by baseline LVMI. Patients were divided into 2 groups based on their median LVMI RR as follows: (1) a poor LVH regression (PR-LVH) group with values below the median LVMI RR; and (2) a good LVH regression (GR-LVH) group with values above the median LVMI RR. The median LVMI RR was 25.4%. There were 88 (50.3%) patients in the PR-LVH group. In the multivariable analysis, 1-week postoperative Zva (odds ratio [OR] 2.777; 95% confidence interval [CI] 1.584–4.869; P<0.001) and baseline LVMI per 10-unit increment (OR 0.974; 95% CI 0.960–0.988; P=0.001) were independent predictors of PR-LVH. The receiver operating characteristic curve analysis identified Zva ≥3.5 mmHg/mL/m²as a cut-off value associated with PR-LVH.

Conclusions: One-week postoperative Zva was a better predictor of improved LVH at 1 year after SAVR than PPM.

Background: Heart failure (HF) management has been improved by guideline-directed medical therapy (GDMT) based on findings of major randomized controlled trials (RCTs). However, the applicability of these findings to real-world HF populations, especially Japan’s current super-aged society, remains uncertain.

Methods and Results: We analyzed findings for chronic HF patients from the KUNIUMI registry, a prospective observational study conducted on Awaji Island, Japan, representative of a super-aged society (aging rate ≈37%). We determined what percentage of these patients met the inclusion criteria as well as the exclusion criteria of 6 major representative RCTs (PARADIGM-HF, PARAGON-HF, DAPA-HF, DELIVER, EMPEROR-Reduced, EMPEROR-Preserved) and compared the incidence of cardiovascular death and HF hospitalization over 3 years for patients who did and did not meet the exclusion criteria. Of the 1,646 patients from the KUNIUMI registry, 225 were eligible for PARADIGM-HF, DAPA-HF and EMPEROR-Reduced, 554 for PARAGON-HF, and 631 for DELIVER and EMPEROR-Preserved. The exclusion percentages for the overall eligible population were 48.4% (PARADIGM-HF), 36.4% (DAPA-HF), 42.7% (EMPEROR-Reduced), 57.9% (PARAGON-HF), 32.3% (DELIVER), and 31.4% (EMPEROR-Preserved). It should be noted that ineligible patients had a poorer prognosis than eligible patients (P<0.05 for each trial).

Conclusions: The population gap between HF patients in major RCTs and the current super-aged society underscores the need for further evidence of GDMT in real-world settings.

Background: It has been thought that neutrophil extracellular traps (NETs) and thrombosis exacerbate COVID-19, but, on the other hand, NETs are an important player in innate immunity. The precise roles of NETs and thrombosis in the course of COVID-19 have not been fully elucidated.

Methods and Results: The roles were investigated in the literature and a new theory was formulated. When neutrophils encounter SARS-CoV-2 in the lung tissue, they undergo NETosis and capture the virus. This capture is triggered by electrostatic interaction between histones in NETs and SARS-CoV-2; histones are highly positively charged, and viruses, including SARS-CoV-2, have a net negative charge under physiological pH. NETs that capture SARS-CoV-2 fall into alveolar capillaries through the collapsed endothelium to spare the lung tissue from the toxicity of NETs. NETs in the microvessels cause microthrombosis; positively charged histones induce the aggregation of negatively charged platelets, which leads to microthrombi. Microthrombi engulfing SARS-CoV-2 are consolidated into fibrin clots, which are eventually degraded by increased fibrinolysis and eliminated from the circulation.

Conclusions: This novel theory suggests that NETosis and microthrombosis are phenomena inevitably elicited in COVID-19, and in combination they are a system newly termed “NETombosis”. Undegraded fibrin clots remaining in the microcirculation may be the cause of the sequelae, because they cause long-lasting circulatory failure in various organs.

Background: The association of each of the recently classified steatotic liver diseases (SLDs), including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD), with new development of ischemic heart disease (IHD) remains unclear.

Methods and Results: We investigated the associations of various SLDs with the development of IHD during a 10-year follow-up period in 13,815 Japanese individuals without a history of IHD (men/women 8,933/4,882; mean age 48 years) who underwent annual health checkups including an abdominal ultrasound examination. Among the participants, 4,639 (33.6%) subjects were diagnosed as having SLDs, and the proportions of subjects with MASLD, MetALD and ALD were 25.4%, 4.7% and 1.9%, respectively. During the follow-up period, 1,963 (16.2%; men/women 1,374 [17.2%]/589 [14.2%]) subjects had new development of IHD. Multivariable Cox proportional hazard model analysis after adjustment of age, sex, estimated glomerular filtration rate (eGFR), current smoking habit, diabetes, hypertension and dyslipidemia showed that the adjusted risk for new onset of IHD was significantly higher in subjects with MASLD (hazard ratio 1.20 [95% confidence interval 1.01–1.55]; P=0.042) than in those without SLD. Other SLDs were not selected as independent risk factors for the development of IHD.

Conclusions: The presence of MASLD, but not other SLDs, is an independent risk factor for new onset of IHD during a 10-year follow-up period.

Background: The effect of Intensified Multifactorial treatments on coronary atherosclerosis in PAtients with Coronary artery disease and Type 2 Diabetes Mellitus (IMPACT-DM) trial was designed to investigate the effects of intensified multifactorial treatments (IMT) on coronary plaque progression in patients with coronary artery disease (CAD) and diabetes.

Methods and Results: In this prospective, randomized, open-label, parallel assignment, multicenter study, eligible patients with diabetes who underwent successful percutaneous coronary intervention in culprit lesions are randomly assigned to receive either IMT or guideline-oriented standard treatments (Control) for 18 months. The IMT are managed according to strict target goals and step-by-step medical treatment protocols based on modern medical treatments. Target goals in IMT and Control groups are set to hemoglobin A1c <6.2% vs. <7.0%; low-density lipoprotein cholesterol <55 mg/dL for any type of CAD vs. <70 mg/dL for acute coronary syndrome, or <100 mg/dL for stable CAD; and blood pressure <120/80 mmHg vs. <130/80 mmHg, respectively. Non-culprit lesions are evaluated using intravascular ultrasound (IVUS) at post-procedure and 18 months follow up. The primary endpoint is absolute changes in percent plaque volumes in non-culprit lesions as assessed using IVUS from post-procedure to 18 months.

Conclusions: The IMPACT-DM trial will clarify the clinical benefits of IMT on non-culprit coronary plaques in patients with diabetes undergoing successful PCI in culprit lesions.

Background: Transcatheter aortic valve replacement (TAVR) improves left ventricular (LV) deformation by aortic stenosis (AS). However, the early effects of TAVR on LV mechanics as assessed by echocardiography have not been fully elucidated.

Methods and Results: Between 2021 and 2024, we included 81 patients who underwent transfemoral TAVR for severe AS. We used the natural logarithm of B-type natriuretic peptide (lnBNP) 1 week after TAVR as an indicator of the early effects on LV mechanics. To determine the association with echocardiographic parameters (LV ejection fraction [LVEF], global longitudinal strain [GLS], E/e′, and Tei index) and postprocedural lnBNP, we used regression models while adjusting for covariates. There were no significant differences in LVEF, GLS or E/e′ between before and after TAVR, but the postprocedural Tei index was significantly higher than the preprocedural Tei index (0.40 vs. 0.26, P<0.01). In a univariate linear regression, the preprocedural LVEF (β=–0.28, P=0.01), GLS (β=–0.24, P=0.04), E/e′ (β=0.36, P<0.01), and Tei index (β=0.27, P=0.02) correlated with postprocedural lnBNP. Regarding the postprocedural parameters, GLS (β=–0.27, P=0.02) and E/e′ (β=0.36, P<0.01) also correlated with postprocedural lnBNP, but the LVEF and Tei index did not. After adjustment for covariates, these correlations remained significant.

Conclusions: Preprocedural echocardiographic parameters reflecting LV function correlated with BNP after TAVR, but the utility of postprocedural parameters may depend on preprocedural LV function or perioperative factors.

Background: Basic fibroblast growth factor (bFGF) is an angiogenic factor with a short half-life. Because recombinant bFGF is in clinical use, we hypothesized that the localization of recombinant bFGF with atelocollagen would have angiogenic effects at the injection site in normal and hind limb ischemic animal models.

Methods and Results: We administered the recombinant bFGF with atelocollagen intramuscularly to hind limbs in normal rabbits or in a mouse model of femoral artery ligation to explore the pharmacological action for ischemia. We evaluated blood flow in the ischemic/normal limb using laser speckle perfusion imaging and the density of blood vessels by pathological examination. At the administration site in normal rabbits, a significant increase in the number of blood vessels was noted at 14 days post-administration of recombinant bFGF with atelocollagen compared with saline or atelocollagen alone. In mice with femoral artery ligation, blood flow and vessels in the ischemic hind limb increased at 2 weeks after injection and more at 4 weeks after injection, and the effect was most significant in mice administered 100 μg of recombinant bFGF with 3% of atelocollagen.

Conclusions: Intramuscular administration of recombinant bFGF with atelocollagen induced angiogenesis between 2 and 4 weeks in both normal and ischemic hind limbs.

Background: Previous reports have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefit patients with heart failure (HF), regardless of left ventricular ejection fraction. However, evidence is limited for patients who are underweight, particularly with a body mass index (BMI) <20 kg/m².

Methods and Results: Between February 2022 and July 2023, 533 patients were hospitalized at the Japanese Red Cross Wakayama Medical Center for acute HF. Excluding those who died during hospitalization, we categorized 488 patients according to their BMI at discharge: <20 kg/m²(n=201), and ≥20 kg/m²(n=287). Among the BMI <20 kg/m²group, SGLT2i was prescribed to 53 patients. The cumulative incidence rates of all-cause mortality at 1 year were significantly different between BMI <20 kg/m²patients with and without SGLT2i (11.8% vs. 36.1%; log-rank P=0.004). In the multivariate Cox proportional hazard models, SGLT2i reduced the risk of all-cause mortality independent of age, frailty, walking speed, decreased albumin level, elevated C-reactive protein level, and prescriptions of renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists. However, among patients who received SGLT2i, the SGLT2i prescription continuation rate at 1 year was not significantly different between the BMI <20 kg/m²and BMI ≥20 kg/m²groups (85.4% vs. 84.6%; log-rank P=0.869).

Conclusions: SGLT2i are feasibly effective and well-tolerated drugs, even for patients with low BMI.