Takeshi Kitai

Initial Surgical Versus Conservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis.

BACKGROUND Current guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS). OBJECTIVES The study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS. METHODS We used data from a large multicenter registry enrolling 3,815 consecutive patients with severe AS (peak aortic jet velocity >4.0 m/s, or mean aortic pressure gradient >40 mm Hg, or aortic valve area <1.0 cm(2)) between January 2003 and December 2011. Among 1,808 asymptomatic patients, the initial AVR and conservative strategies were chosen in 291 patients, and 1,517 patients, respectively. Median follow-up was 1,361 days with 90% follow-up rate at 2 years. The propensity score-matched cohort of 582 patients (n = 291 in each group) was developed as the main analysis set for the current report. RESULTS Baseline characteristics of the propensity score-matched cohort were largely comparable, except for the slightly younger age and the greater AS severity in the initial AVR group. In the conservative group, AVR was performed in 41% of patients during follow-up. The cumulative 5-year incidences of all-cause death and heart failure hospitalization were significantly lower in the initial AVR group than in the conservative group (15.4% vs. 26.4%, p = 0.009; 3.8% vs. 19.9%, p < 0.001, respectively). CONCLUSIONS The long-term outcome of asymptomatic patients with severe AS was dismal when managed conservatively in this real-world analysis and might be substantially improved by an initial AVR strategy. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140).

Clinical Outcomes of Medical Therapy and Timely Operation in Initially Diagnosed Type A Aortic Intramural Hematoma: A 20-Year Experience

Background— The management of aortic intramural hematoma (IMH) involving the ascending aorta (type A) has not been well-established. The purpose of this study was to clarify the long-term clinical outcomes of patients with type A IMH who were treated with medical therapy and timely operation. Methods and Results— Clinical data including operative mortality, IMH-related events, and long-term survival were retrospectively reviewed in 66 patients with type A IMH, who were admitted to our institution from 1986 to 2006. Emergent surgical repair was performed in 16 (24%) patients because of severe complications, whereas 50 patients were treated with initial medical therapy. In medically treated patients, 15 (30%) patients who demonstrated progression to classic dissection or increase in hematoma size within 30 days underwent surgical repair except for 2 patients who refused surgery. The 30-day mortality rate was 6% with emergent surgery and 4% with supportive medial therapy. There were 7 late deaths and the actuarial survival rates of all patients were 96±3%, 94±3%, and 89±5% at 1, 5, and 10 years, respectively. In medically treated patients, maximum aortic diameter was the only predictor of early and late progression of ascending IMH (hazard ratio, 4.43; 95% CI, 2.04–9.64; P<0.001). Aortic diameter ≥50 mm predicted progression of ascending IMH with the positive and negative value of 83% and 84%, respectively. Conclusions— Combination of medical therapy and timely operation resulted in favorable long-term clinical outcomes in patients with type A IMH.

Impact of New Development of Ulcer-Like Projection on Clinical Outcomes in Patients With Type B Aortic Dissection With Closed and Thrombosed False Lumen

Background— The purpose of this study was to investigate the clinical importance of newly developed ulcer-like projection (ULP) in patients with type B aortic dissection with closed and thrombosed false lumen (AD with CTFL), which is better known as aortic intramural hematoma. Methods and Results— A total of 170 patients with acute type B AD with CTFL were admitted to our institution from 1986 to 2008 and treated initially with medical therapy. There were 31 late deaths, including 9 cases of aortic rupture. The actuarial survival rates of all patients were 99%, 89%, 83% at 1, 5, and 10 years, respectively. A total of 62 (36%) patients showed new ULP development within 30 days from the onset. Patients who had ULP showed significantly poorer survival rates than patients who did not have ULP (P=0.037). Development of ULP was also associated with a significant increase in adverse aorta-related events (P<0.001). In addition, patients with ULP in the proximal descending thoracic aorta (PD) showed significantly higher aorta-related event rates than patients without ULP in the PD (P<0.001). Initial aortic diameter (hazard ratio, 3.55; P<0.001) and development of ULP in PD (hazard ratio, 3.79; P=0.003) were the strongest predictors of adverse aorta-related events. Conclusions— Initial aortic diameter and development of ULP in the PD are both strong predictors of adverse aorta-related events in patients with type B AD with CTFL. Patients with newly developed ULP should be more carefully followed up with close surveillance imaging than those without ULP.

Detection of Intimal Defect by 64-Row Multidetector Computed Tomography in Patients With Acute Aortic Intramural Hematoma

Background— Previous pathological and clinical studies demonstrated an intimal defect in patients with acute aortic intramural hematoma (IMH). The purpose of this study was to investigate the prevalence and clinical outcome of intimal defect detected by multidetector computed tomography (MDCT) in patients with IMH. Methods and Results— We retrospectively analyzed 38 consecutive patients with IMH in whom 64-row MDCT was performed during the acute phase (median, 5 days from the onset). Intimal defect was defined as continuity disruption of the inner layer of thrombosed false lumen, which could be detected by 1-mm axial and longitudinal interactive multiplanar reformation images. Clinical outcome of intimal defect was assessed in patients with type B IMH (n=32). A total of 48 lesions in 27 (71%) patients were recognized as intimal defects. The incidence of intimal defect was not affected by the timing of MDCT examination (1 to 3 days, 79%; 4 to 7 days, 58%; 8 to 14 days, 75%; P=0.56). In type B IMH, 16 (76%) of 21 patients with intimal defect showed progression (enlargement or progression to aortic aneurysm) in the chronic phase. In contrast, all 11 patients without intimal defect had complete resorption of hematoma. In lesion-based analysis, a depth of intimal defect of ≥5 mm predicted progression with sensitivity, specificity, and positive and negative predictive values of 84%, 95%, 94%, and 86%, respectively. Conclusions— A considerable portion of patients with IMH showed intimal defect detected by MDCT even in the very early stage, and defects frequently enlarged. Patients with intimal defect should be carefully followed up with serial imaging.

Clinical outcomes in non-surgically managed patients with very severe versus severe aortic stenosis

Objective The management of asymptomatic severe and very severe aortic stenosis (AS) remains unestablished. This study aimed to investigate the clinical outcomes of severe versus very severe AS patients. Design A single centre, retrospective cohort study. Patients and Methods The study retrospectively reviewed 108 conservatively treated patients with severe AS (a maximal jet velocity ≥4.0 m/s, or mean aortic pressure gradient (MPG) ≥40 mm Hg, or an aortic valve area (AVA) <1.0 cm2) and 58 patients with very severe AS (a maximal jet velocity ≥5.0 m/s, or MPG ≥50 mm Hg or an AVA <0.6 cm2). Clinical outcomes were compared between the two groups, considering the existence of symptoms. Main Outcome Measures All-cause mortality and valve-related event, defined by a composite of cardiac death and hospitalisation because of heart failure. Results Mean follow-up was 5.5±3.1 years. Fifty-six patients (52%) with severe AS and 20 patients (34%) with very severe AS were asymptomatic. Very severe AS had poorer survival and valve-related event-free survival than severe AS at 3 years (77% vs 88%, p<0.01; 75% vs 88%, p<0.001, respectively). In addition, the 3-year survival and valve-related event-free survival of asymptomatic very severe AS were comparable with symptomatic severe AS, but they were significantly worse than asymptomatic severe AS (p<0.01 and p<0.001, respectively). Conclusions Surgery should always be considered in very severe AS regardless of symptoms, and particular attention needs to be paid to their extremely poor outcomes.

Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy

AimsTo prospectively evaluate the relationship between left atrial volume (LAV) and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM).MethodsWe enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61 ± 13 years) who met inclusion criteria were followed for 30.8 ± 10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE), a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained.ResultsMACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths). Maximum LAV, minimum LAV, and LAV index (LAVI) corrected for body surface area (BSA) were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3 ± 25.0 vs. 51.9 ± 16.0 ml, p = 0.005; minimum LAV: 33.9 ± 15.1 vs. 26.2 ± 10.9 ml, p = 0.008; LAVI: 40.1 ± 15.4 vs. 31.5 ± 8.7 ml/mm2, p = 0.0009), while there were no differences in the other echocardiographic parameters.LAV/BSA of ≥ 40.4 ml/m2 to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%.ConclusionLAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.

Clinical Effectiveness of Tolvaptan in Patients With Acute Heart Failure and Renal Dysfunction

BACKGROUND More efficacious and/or safer decongestive therapy is clearly needed in acute heart failure (AHF) patients complicated by renal dysfunction. We tested the hypothesis that adding tolvaptan, an oral vasopressin-2 receptor antagonist, to conventional therapy with loop diuretics would be more effective treatment in this population. METHODS AND RESULTS A multicenter, open-label, randomized control trial was performed, and 217 AHF patients with renal dysfunction (estimated glomerular filtration rate 15-60 mL • min(-1) • 1.73 m(-2)) were randomized 1:1 to treatment with tolvaptan (n=108) or conventional treatment (n=109). The primary end point was 48-hour urine volume. The tolvaptan group showed more diuresis than the conventional treatment group (6464.4 vs 4999.2 mL; P <.001) despite significantly lower amounts of loop diuretic use (80 mg vs 120 mg; P <.001). Dyspnea relief was achieved significantly more frequently in the tolvaptan group at all time points within 48 hours except 6 hours after enrollment. The rate of worsening of renal function (≥0.3 mg/dL increase from baseline) was similar between the tolvaptan and conventional treatment groups (24.1% vs 27.8%, respectively; P =.642). CONCLUSIONS Adding tolvaptan to conventional treatment achieved more diuresis and relieved dyspnea symptoms in AHF patients with renal dysfunction. CLINICAL TRIAL REGISTRATION URL: http://www.umin.ac.jp/ctr/index/htm/ Unique identifier: UMIN000007109.

Exploring the Microbiome in Heart Failure

Recent years have brought interesting insights into the human gut microbiota and have highlighted its increasingly recognized impact on cardiovascular (CV) diseases, including heart failure (HF). Changes in composition of gut microbiota, called dysbiosis, can trigger systemic inflammation, which is known to be involved in the pathophysiology of HF. Trimethylamine N-oxide (TMAO), which is derived from gut microbiota metabolites of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. Elevated TMAO levels have been reported to be associated with poor outcomes in patients with both HF and chronic kidney disease (CKD). Dysbiosis of gut microbiota can contribute to higher levels of TMAO and the generation of uremic toxins, progressing to both HF and CKD. Therefore, this bidirectional relationship between HF and CKD through gut microbiota may be a novel therapeutic target for the cardiorenal syndrome. However, the mechanisms by which gut microbiota could influence the development of heart failure are still unknown, and there are still some questions regarding the causative effects of TMAO and the underlying mechanistic link that explains how TMAO might directly or indirectly promote CV diseases including HF. Further studies are warranted to clarify the function of TMAO on the pathophysiology of cardiorenal syndrome and the handling of TMAO levels by the kidneys.

Detection of severe stenosis and total occlusion in the left anterior descending coronary artery with transthoracic Doppler echocardiography in the emergency room.

Background: The noninvasive measurement of coronary flow velocity in the left anterior descending artery (LAD) has recently been realized by using the transthoracic Doppler echocardiography (TTDE). A couple of investigations demonstrated that the diastolic‐to‐systolic peak velocity ratio (DSVR) by TTDE is a simple and noninvasive method for the detection of severe stenosis in the elective settings. However, the usefulness of DSVR by TTDE in the emergency settings has not been evaluated. Objective: The purpose of this study was to assess the clinical feasibility to document the LAD flow by TTDE in emergency patients who complained of chest pain. Methods: We studied 49 consecutive patients with acute coronary syndrome who were going to undergo emergency coronary angiography (CAG) for the anatomical diagnosis and the facilitated percutaneous coronary intervention (PCI). Prior to CAG, we recorded the LAD flow by TTDE and measured the diastolic peak velocity (DVp), systolic peak velocity (SVp), and their ratio, DSVR (DVp/SVp) of LAD flow. Results: By CAG, the culprit lesions actually resided in the proximal LAD in 36 patients. Among the 36 patients, we detected the Doppler LAD flow in 29. Five out of 7 patients who were unable to detect the LAD flow revealed total occlusions by CAG. DSVR of the LAD is significantly lower in 17 patients who showed severe stenoses (>90%) than those in the rest of 12 patients who did not show such critical stenoses (1.44 ± 0.16 vs 2.10 ± 0.26, P < 0.0001). Conclusion: In the emergency settings, a noninvasive assessment of the LAD flow by TTDE accurately estimates the critical stenotic lesions of the LAD.

Intrarenal Venous Flow: A Window Into the Congestive Kidney Failure Phenotype of Heart Failure?

Although the importance of congestion in the disease progression of heart failure has long been recognized [(1)][1], much has focused on how cardiac impairment can lead to renal dysfunction. Over the past decade, there is increasing recognition that the ability of the kidneys to compensate for fluid