Who Can Receive Clinical Benefit from Mid-Term Vericiguat Add-on Therapy Among Patients with Systolic Heart Failure Receiving Quadruple Medical Therapy?

Vericiguat, a soluble guanylate cyclase stimulator known for augmenting cyclic guanosine monophosphate production, has garnered substantial clinical attention in patients with systolic heart failure. Despite its proven efficacy, discerning the specific subset of individuals who can enjoy clinical advantages from vericiguat therapy in contemporary real-world clinical practice, particularly among the individuals undergoing "quadruple medical therapy" comprising administration of a beta-blocker, angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonist, and sodium-glucose co-transporter 2 inhibitor, remains an unresolved query. This study involved patients undergoing 3-month vericiguat therapy alongside complete quadruple medical therapy in a contemporary real-world clinical practice. Baseline characteristics associated with the primary outcome, defined as a reduction in serum NT pro-B-type natriuretic peptide (BNP) levels over the 3-month therapeutic duration, were scrutinized. A cohort of 24 patients (median age: 66 years; 20 males) were included. All participants diligently adhered to the 3-month vericiguat therapy in conjunction with the quadruple medical regimen. A higher baseline systolic blood pressure emerged as an independent factor linked to the primary outcome, yielding an adjusted odds ratio of 1.31 (95% confidence interval: 1.03-1.65, P = 0.026) at a threshold of 105 mmHg. This threshold notably stratified the trajectories of serum NT pro-BNP levels during the 3-month vericiguat therapy. In conclusion, preservation of baseline systolic blood pressure emerged as a pivotal determinant for reaping the clinical benefits from mid-term vericiguat therapy among patients with systolic heart failure receiving quadruple medical therapy.

Introduction of novel intravascular ultrasound preceding with angled guiding catheter (I-PAD) technique to treat chronic total occlusions in peripheral artery disease.

BACKGROUND: The optimal endovascular treatment (EVT) for chronic total occlusion (CTO) lesions in patients with peripheral artery disease (PAD) has remained unestablished. We encountered a patient with PAD in whom CTO was successfully treated using a novel technique that involved intravascular ultrasound (IVUS) and angled guiding catheter: IVUS Preceding with Angled guiDing catheter (I-PAD) technique. CASE PRESENTATION: A 74-year-old male presented with intermittent claudication attributed to CTO of the right external iliac artery. EVT was performed via the right common femoral artery. We retrogradely advanced the I-PAD system (i.e. partially extending the IVUS transducer portion from the tip of the angled guiding catheter) in the CTO lesion under the real-time guidance of IVUS imaging. We successfully traversed the CTO lesion without the use of a guidewire in approximately three minutes. The procedure concluded successfully without any procedure-related complications, following optimal stenting. CONCLUSIONS: The I-PAD might be an effective technique to accurately, quickly, and safely pass through CTO lesions.

Arterioureteral fistula and refractory fatal pseudo-aneurysm in a patient receiving kidney transplantation.

Arterioureteral fistula represents a rare yet consequential urological complication characterized by persistent and refractory urinary tract bleeding. Its emergence typically involves aneurysm formation, presenting significant life-threatening implications. Nonetheless, its infrequency contributes to sparse documentation of incidences in post-kidney transplant recipients, thereby fostering numerous uncertainties concerning associated risks. A 67-year-old male patient, afflicted with end-stage renal failure and a history of urinary tract infection, underwent a living donor kidney transplant four months prior. Complications involving intraoperative bleeding necessitated the prolonged placement of a ureteral stent post-surgery. Subsequently, he experienced an abrupt onset of ureteral bleeding accompanied by shock, later diagnosed via contrast-enhanced computed tomography as pseudo-aneurysm formation in the right external iliac artery proximal to the allograft renal artery anastomosis, in conjunction with a fistula formation involving the donor ureter. Despite repeated attempts at intervention with covered stenting, the aneurysm persisted and proved refractory to resolution. Tragically, seven months later, the aneurysm ruptured, culminating in the demise of the patient. Our report details a case involving perioperative complications following kidney transplantation, persistent bacteriuria, and prolonged ureteral stenting, ultimately leading to the development of an arterioureteral fistula. Despite undergoing stent graft insertion as an intervention, the patient succumbed to aneurysm rupture associated with the arterioureteral fistula. This condition, though rare, can prove fatal following kidney transplantation. Consequently, future endeavors in this domain necessitate an emphasis on optimizing risk management, refining diagnostic approaches, and devising more effective therapeutic strategies to mitigate such complications.

A case of destination therapy for post-fulminant myocarditis with myelodysplastic syndrome.

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome.

The Impact of the Withdrawal of SGLT2 Inhibitors on Clinical Outcomes in Patients with Heart Failure.

Background: The clinical impact of the withdrawal of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on all-cause readmission in patients with heart failure remains unknown. Methods: We enrolled a total of 212 consecutive patients who were hospitalized for heart failure and received SGLT2i during their index hospitalization between February 2016 and July 2022. Of these patients, 51 terminated SGLT2i during or after their index hospitalization. We evaluated the prognostic impact of the withdrawal of SGLT2i on the primary outcome, which was defined as the all-cause readmission rate/times. Results: Over a median of 23.2 months, all-cause readmission occurred in 38 out of 51 patients (74.5%) withdrawn from SGLT2i and 93 out of 161 patients (57.8%) with continuation of SGLT2i (p = 0.099). The incidence of all-cause readmissions per year was 0.97 [0-1.50] in patients withdrawn from SGLT2i and 0.50 [0-1.03] in patients with continuation of SGLT2i (p = 0.030). There was no significant difference in total medical costs (62,906 [502-187,246] versus 29,236 [7920-180,305] JPY per month, p = 0.866) between both patient groups. Conclusions: Termination of SGLT2i may be associated with incremental all-cause readmission and no benefit in reducing total medical costs.

A Lower Remote Dielectric Sensing Value Was Associated with Hypovolemia and Worse Clinical Outcomes.

Background: Remote dielectric sensing (ReDS) systems can estimate the amount of lung fluid non-invasively and easily without expert techniques. The correlation between the elevated ReDS value and other modalities that estimate pulmonary congestion has been validated. The clinical implications of lower ReDS values, which may indicate hypovolemia, remain unknown. Methods: A total of 138 patients who were hospitalized for various cardiovascular-related problems and underwent ReDS value measurements at the index discharge in a blinded manner to the attending clinicians were eligible for inclusion. Patients with ReDS values > 30%, indicating the presence of pulmonary congestion, were excluded. The prognostic impact of lower ReDS values on all-cause readmission after index discharge was evaluated. Results: A total of 97 patients were included. The median age was 78 years, and 48 were men. The median ReDS value at index discharge was 26% (23%, 27%). A lower ReDS value correlated with smaller inferior vena cava maximum diameters (r = 0.46, p < 0.001) and higher blood urea nitrogen/creatinine ratios (r = -0.35, p < 0.001). A lower ReDS value (≤25%) was associated with a risk of all-cause readmissions with an unadjusted hazard ratio of 2.68 (95% confidence interval 1.09-6.59, p = 0.031) and an adjusted hazard ratio of 2.30 (95% confidence interval 0.92-5.78, p = 0.076). Its calculated cutoff of 25% significantly stratified the cumulative incidence of the primary outcome (36% versus 17%, p = 0.038). Conclusions: A lower ReDS value may indicate hypovolemia and be associated with the risk of all-cause readmission in patients hospitalized for cardiovascular diseases.

Short-term impact of kampo goreisan in patients with congestive heart failure refractory to tolvaptan-incorporated medical therapy.

We often encounter patients with congestive heart failure refractory to conventional diuretics therapy. Kampo goreisan (Tsumura &Co. Tokyo, Japan) is receiving great concern in mediating body water balance, particularly for such a cohort. However, its detailed biological mechanism remains uncertain. Patients who received goreisan to treat congestive heart failure refractory to tolvaptan-incorporated medical therapy were prospectively included and observed for one week during the therapeutic period. The change in urine biomarkers during the first 24 h was assessed as a primary concern. Baseline factors associated with an increase in urine volume during the first 24 h were investigated as a secondary concern. A total of 18 patients were included. Median age was 81 (77, 86) and 12 (67%) were men. During the first 24 h after the initiation of goreisan, urine cyclic AMP tended to decrease, urine aquaporin-2 decreased significantly, urine osmolality decreased significantly, and urine volume tended to increase. Baseline higher common logarithm of plasma B-type natriuretic peptide was associated with any increases in urine volume during the first 24 h with an odds ratio of 73.2 (95% confidence interval 1.04-5149, p = 0.048). Baseline plasma B-type natriuretic peptide level had a positive correlation with a change in urine volume between baseline and day 1 (r = 0.533, p = 0.026). Goreisan may increase urine volume even in patients with congestive heart failure refractory to tolvaptan-incorporated medical therapy by modulating aquaporin-2 systems in the collecting duct, particularly in individuals with advanced heart failure accompanying significant congestion. Goreisan may have a regulatory effect on body fluid, rather than just forcing aquaresis.

Small Left Ventricular Size Is a Risk Factor for Recurrent Pericardial Effusion after Percutaneous Drainage.

Background: Significant pericardial effusion requires percutaneous drainage. Some patients experience recurrent pericardial effusion following index drainage, but its risk factors remain unknown. Such knowledge should further improve the clinical management of individuals presenting with pericardial effusion for risk stratification and the construction of therapeutic and management strategies beforehand. Methods: Patients who underwent percutaneous drainage for pericardial effusion between 2018 and 2023 were retrospectively included and were followed for 2 years or until November 2023. Baseline factors associated with recurrent pericardial effusion that required percutaneous drainage again were investigated to identify the high-risk cohort. Results: A total of 39 patients (83 years on median, 28 males) were included. During the 2-year observation period, 11 patients had the primary outcome. The left ventricular end-diastolic diameter at baseline was independently associated with the primary outcome with an adjusted hazard ratio of 0.88 (95% confidence interval 0.80-0.97, p = 0.013) with a cutoff of 42 mm, which significantly stratified the cumulative incidence of the primary outcome (53% versus 10%, p = 0.011). Conclusions: Recurrent pericardial effusion after percutaneous drainage is not a rare phenomenon. A smaller left ventricular endo-diastolic diameter was an independent risk factor for recurrent pericardial effusion. The clinical implications of our findings in daily clinical practice should be validated in future prospective studies. Further studies are warranted to clarify the underlying causality between them.

Impella support for refractory cardiogenic shock accompanied by diabetic ketoacidosis: a case report.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are strongly recommended in patients with heart failure, regardless of the presence of diabetes mellitus. A 74 year-old woman with a reduced left ventricular ejection fraction and diabetes mellitus (the types were unknown), receiving insulin and SGLT2 inhibitor, was hospitalized for altered consciousness with systemic hypotension. Upon admission, she was diagnosed with cardiogenic shock due to diabetic ketoacidosis. Intensive fluid resuscitation under Impella CP support successively improved her metabolic acidosis, preventing worsening pulmonary congestion by mechanically unloading the heart. After hemodynamic stabilization, she was diagnosed with type 1 diabetes mellitus for the first time. She was discharged on day 54 and was followed for 6 months without any recurrences. We must remain vigilant regarding the risk of diabetic ketoacidosis in patients using SGLT2 inhibitors, particularly those on insulin therapy or with diabetes mellitus of unknown types. Impella device shows promise as a circulatory support system in alleviating the left ventricle's workload and averting exacerbated pulmonary congestion, especially in cases where patients necessitate aggressive fluid replacement therapy, such as in the treatment of diabetic ketoacidosis concurrent with compromised cardiac function.

Clinical Implications of Remote Dielectric Sensing-Guided Management.

Background: Remote dielectric sensing (ReDS) systems can quantify the degree of pulmonary congestion rapidly and non-invasively. However, the clinical implications of ReDS-guided medication adjustment remain uncertain. Methods: Patients hospitalized to treat cardiovascular diseases, including heart failure, valvular disease, and coronary artery disease, and underwent ReDS measurement before index discharge between 2021 and 2022 were included. According to our institutional protocol, ReDS values were blinded to the attending clinicians until February 2022 (blind period). After the period, ReDS values were timely opened to the attending clinicians, and medications such as diuretics were adjusted according to the ReDS values (target value between 20% and 35%) before index discharge (open period). A composite primary outcome of all-cause death and heart failure readmissions was compared between the two groups. Results: A total of 183 patients were included (median 79 years old, 101 men), consisting of 138 patients in the blind period and 45 patients in the open period. During a median of 646 (401, 818) days after the index discharge, 33 patients experienced the primary outcome of interest. Management during the open period, where medications were adjusted according to ReDS values, was independently associated with a lower incidence of the primary outcome with an adjusted hazard ratio of 0.22 (95% confidence interval 0.05-0.94, p = 0.041), as compared with those of the blind period. Conclusions: According to the findings of the present retrospective study, ReDS-guided management may have the potential to reduce the risk of mortality and heart failure admission in individuals hospitalized for cardiovascular diagnoses. Further prospective randomized control trials involving those with a variety of background etiologies and clinical scenarios are warranted to validate our findings and establish optimal ReDS-guided management.

Paradoxical prognostic impact of severe aortic stenosis following trans-catheter aortic valve implantation.

BACKGROUND: Aortic valve replacement is recommended for patients with "very severe" aortic stenosis (AS), irrespective of symptomatic manifestation. Nonetheless, the prognostic ramifications of "very severe" AS, as opposed to "severe" AS, subsequent to trans-catheter aortic valve implantation (TAVI) remain enigmatic. METHODS: We enrolled consecutive patients who received TAVI at our institute between May 2015 and April 2021. We scrutinized the impact of baseline "very severe" AS upon 3-year all-cause death or heart failure hospitalization following TAVI, in comparison to "severe" AS. RESULTS: A total of 239 patients (84.8 ±â€¯5.4 years old, 58 men) were included. Baseline "very severe" AS was observed in 65 (27 %) patients, who exhibited more advanced hypertrophy and higher B-type natriuretic peptide levels compared to those with "severe" AS (p < 0.05 for both). Baseline "very severe" AS was paradoxically associated with higher freedom from the primary endpoint following TAVI compared to those with "severe" AS (p = 0.01). CONCLUSIONS: The presence of baseline "very severe" AS was paradoxically associated with improved clinical outcomes subsequent to TAVI, in contrast to the cases of "severe" AS.

Chronic Effects of Adaptive Servo-Ventilation Therapy on Mortality and the Urgent Rehospitalization Rate in Patients Experiencing Recurrent Admissions for Heart Failure　- A Multicenter Prospective Observational Study (SAVIOR-L).

BACKGROUND: This study investigated whether the chronic use of adaptive servo-ventilation (ASV) reduces all-cause mortality and the rate of urgent rehospitalization in patients with heart failure (HF).Methods and Results: This multicenter prospective observational study enrolled patients hospitalized for HF in Japan between 2019 and 2020 who were treated either with or without ASV therapy. Of 845 patients, 110 (13%) received chronic ASV at hospital discharge. The primary outcome was a composite of all-cause death and urgent rehospitalization for HF, and was observed in 272 patients over a 1-year follow-up. Following 1:3 sequential propensity score matching, 384 patients were included in the subsequent analysis. The median time to the primary outcome was significantly shorter in the ASV than in non-ASV group (19.7 vs. 34.4 weeks; P=0.013). In contrast, there was no significant difference in the all-cause mortality event-free rate between the 2 groups. CONCLUSIONS: Chronic use of ASV did not impact all-cause mortality in patients experiencing recurrent admissions for HF.

Prognostic impact of insomnia in patients receiving trans-catheter aortic valve replacement.

BACKGROUND: The presence of insomnia exhibits a profound association with diverse cardiovascular pathologies. However, its prognostic implications in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis remain ambiguous. METHODS: This retrospective study enrolled patients who underwent TAVR for severe aortic stenosis at a prominent academic center from 2015 to 2022. The impact of insomnia, operationally defined as the prescription of soporific agents, on the two-year composite primary outcome comprising all-cause mortality and hospital readmissions was scrutinized. RESULTS: A cohort of 345 patients (median age 85 years, 99 males) was encompassed in the analysis. All subjects underwent successful TAVR and subsequent discharge. The presence of insomnia (N = 91) emerged as an independent predictor of the two-year composite endpoint, with an adjusted hazard ratio of 1.66 (95 % confidence interval 1.08-2.57, p = 0.022), significantly delineating the two-year cumulative incidence of the primary endpoint (40 % versus 30 %, p = 0.035). CONCLUSION: Approximately one-fourth of TAVR candidates manifested symptoms of insomnia, a condition autonomously correlated with heightened mortality and morbidity following the TAVR procedure. The optimal strategy for addressing insomnia in TAVR candidates constitutes a paramount consideration for future interventions.

Two-Year Clinical Outcome of MitraClip Transcatheter Edge-to-Edge Repair From the J-MITRA Registry Data.

BACKGROUND: The introduction of transcatheter edge-to-edge repair for moderate-to-severe or severe mitral regurgitation (MR) utilizing the MitraClip system became reimbursed and clinically accessible in Japan in April 2018. This study presents the 2-year clinical outcomes of all consecutively treated patients who underwent MitraClip implantation in Japan and were prospectively enrolled in the Japanese Circulation Society-oriented J-MITRA registry.Methods and Results: Analysis encompassed 2,739 consecutive patients enrolled in the J-MITRA registry with informed consent (mean age: 78.3±9.6 years, 1,550 males, STS risk score 11.7±8.9), comprising 1,999 cases of functional MR, 644 of degenerative MR and 96 in a mixed group (DMR and FMR). The acute procedure success rate was 88.9%. After MitraClip implantation, >80% exhibited an MR grade ≤2+ and the trend was sustained over the 2 years. Within this observation period, the mortality rate was 19.3% and the rate of heart failure readmissions was 20.6%. The primary composite endpoint, inclusive of cardiovascular death and heart failure readmission, was significantly higher in patients with functional MR than in with degenerative MR (32.0% vs. 17.5%, P<0.001). CONCLUSIONS: The 2-year clinical outcomes after MitraClip implantation were deduced from comprehensive data within an all-Japan registry.

Pegylated-liposomal Doxorubicin-induced Glomerular Thrombotic Microangiopathy.

Pegylated liposomal doxorubicin (PLD) has emerged as a recent innovation within the realm of antineoplastic agents, distinguished by its incorporation of doxorubicin within the liposomal bilayer. Given the low risk of cardiotoxicity, the clinical use of PLD has been expanding. We encountered a patient who underwent extended PLD therapy for recurrent malignancy and subsequently developed PLD-associated thrombotic microangiopathy, which was diagnosed by a detailed pathophysiological assessment. This case underscores the importance of considering thrombotic microangiopathy as a potential differential diagnosis in patients presenting with unexplained hypertension and renal impairment during prolonged PLD monotherapy.