Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

Patients undergoing transplantation for CHD have a good late survival if they survive the early post-operative period. Risk factors for reduced survival are older age at transplant and a previous Fontan operation.

In heart failure, oxygen has a detrimental effect on cardiac output, stroke volume, pulmonary capillary wedge pressure and systemic vascular resistance. These changes are independent of sympathetic activity and ventilation.

Objective-Intravascular ultrasound studies describe ruptured coronary plaques at sites remote from the culprit lesion in patients with acute myocardial infarction (MI), suggesting multifocal plaque vulnerability. However, the role of intravascular ultrasound in the diagnosis of lesion vulnerability before rupture is unclear. Methods and Results-We compared morphology and frequency of ulceration of additional plaques proximal to the culprit lesion in 105 patients treated with emergent stenting during an evolving, acute MI in the CADILLAC study and 92 patients with stable/subacute presentation who underwent elective stenting. Additional plaques proximal to the culprit lesion were found in 52 (50%) and 54 (59%) patients in the acute MI and stable/subacute group, respectively. The prevalence of ulceration was significantly higher in the acute MI than in the stable/subacute group (19% versus 4%; Pϭ0.014). However, there was no significant difference in other morphological lesion characteristics. Key Words: acute coronary syndromes Ⅲ plaque vulnerability Ⅲ intravascular ultrasound Ⅲ atherosclerosis imaging Ⅲ plaque rupture R upture or superficial erosion of vulnerable coronary atheromata are the major pathologic events initiating acute myocardial infarctions (MIs). 1-5 However, recent histologic investigations demonstrate that episodes of plaque rupture are frequent and only occasionally result in acute coronary syndromes (ACS). 6 -8 Clinical, in vivo imaging studies in patients presenting with ACS have demonstrated lesions with characteristics of plaque rupture at multiple sites other than the culprit lesion. 9 -12 Presumably, such patients have a temporary underlying milieu conducive to the development of multifocal plaque ulceration. This systemic vulnerability at the time of acute MI is associated with evidence of systemic inflammation and may explain the high propensity for recurrent acute coronary events. [13][14][15] Intravascular ultrasound (IVUS) can reliably identify overall plaque burden and morphological characteristics of individual lesions in the entire coronary tree. 16 Culprit lesions in patients with ACS are consistently associated with plaque echolucency, ulceration, and positive arterial remodeling. [17][18][19] However, it is unknown if multifocal plaque vulnerability in patients with acute MI is associated with specific morphological characteristics of plaques distant from the culprit lesion. We therefore compared morphology and frequency of ulceration of additional plaques proximal to the culprit lesion in patients with acute MI and stable/subacute clinical presentation. The high-risk patient group, with a high anticipated frequency of vulnerable lesions, was enrolled from a prospective multicenter study of stenting or balloon angioplasty during acute, evolving MI. A low-risk group, with a low anticipated frequency of vulnerable lesions, included patients with stable/subacute clinical presentation undergoing elective stenting. Conclusions-Additional Methods Patient PopulationThe acute MI subgroup...

To determine if peripheral angiotensin II (Ang II) prejunctional receptors facilitating NE release exist in humans, we used 13H INE kinetic methodology to measure forearm NE spillover during intrabrachial arterial Ang II infusions in eight normal male subjects. We used the following protocol to optimize conditions for demonstrating these receptors: (a) lower body negative pressure (-15 mmHg) to increase sympathetic nerve activity to skeletal muscle; and (b) intraarterial nitroprusside to maintain a high constant forearm blood flow (-10 ml/ min* 100 ml) to maximize the proportion of neuronally released NE that spills over into the circulation. During lower body negative pressure, the following were infused intraarterially for three consecutive 20-min periods: saline, Ang II (4 ng/min), and Ang 11( 16 ng/min). During the Ang II infusions, forearm venous NE increased significantly from 173 to 189 and 224 pg/ml (P < 0.01), and forearm NE spillover increased from 384 to 439 and 560 ng/min. 100 ml (P < 0.05 for high Ang II). Forearm NE clearance was unchanged. During low and high dose Ang II, the plasma venous Ang II concentrations were 25 and 97 pM, respectively. Since normal subjects increase plasma Ang II from 4 to 20-22 pM with exercise, standing, or diuretic administration, and patients with severe congestive heart failure can have a plasma Ang II of -25 pM at rest, we suggest that Ang II might facilitate NE release in severe congestive heart failure, especially under conditions of stress. (J. Clin. Invest. 1994. 93:684-691.) Key words: congestive heart failure* angiotensin-converting enzyme inhibitors . 13H1-norepinephrine kinetics . norepinephrine spillover

These results indicate that both diltiazem and lisinopril are safe for treatment of hypertension after heart transplantation, although titrated monotherapy with either drug controlled the condition in < 50% of patients.

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