Wolsk Emil, Jürgens Mikkel, Schou Morten, Ersbøll Mads, Hasbak Philip, Kjaer Andreas, Zerahn Bo, Høgh Brandt Niels, Haulund Gæde Peter, Rossing Peter, Faber Jens, Kistorp Caroline Michaela, Gustafsson Finn
Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen, Denmark.
Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
ESC Heart Fail. 2024 Dec;11(6):3551-3558. doi: 10.1002/ehf2.14929. Epub 2024 Jul 28.
Patients with type 2 diabetes (T2D) have a high prevalence of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF), which in turn leads to an increased risk of hospitalization and death. However, the factors of risk and their relative importance in leading to higher left ventricular filling pressures are still disputed. We sought to clarify the associations of a wide range of invasive and non-invasive risk factors with cardiac filling pressures in high-risk T2D patients.
Patients with T2D at high risk of cardiovascular events were prospectively enrolled in this study. Participants were thoroughly phenotyped including right heart catheterization at rest and during exercise, echocardiography, urinary excretion of albumin (UACR), and quantification of their myocardial blood flow rate (MFR) using cardiac Rb-PET/CT. Of the 37 patients included in the study, 22 (59%) patients met invasive criteria for HFpEF. Only 2 out of 39 variables emerged as independent factors associated with left ventricular filling pressure as assessed by pulmonary capillary wedge pressure (PCWP) at rest; history of hypertension (coefficient: 2.6 mmHg [0.3; 5.0], P = 0.030) and MFR (P = 0.026). We found a significant inverse association between MFR and PCWP with a coefficient of -2.3 mmHg (-4.3; -0.3) in PCWP per integer change of MFR. The MFR ranged from 1.18 to 3.68 in our study, which corresponds to a difference in PCWP of approximately 6 mmHg between patients with the lowest compared to the highest MFR. During exercise, only 2 variables emerged as borderline independent factors associated with PCWP: myocardial flow reserve (coefficient: -4.4 [-9.6; 0.8], P = 0.091) and beta-blockers use (coefficient: 6.1 [-0.1; 12.4], P = 0.053).
In patients with type 2 diabetes without known HFpEF but risk factors for cardiovascular disease, myocardial blood flow rate was independently associated with PCWP at rest across the range from normal to abnormal left heart filling pressures. A clinically significant difference of 6 mmHg in PWCP was attributable to differences in MFR in patients with the lowest compared with the highest MFR values. This suggests that strategies than attenuate microvascular dysfunction could slow progression of increased left ventricular left heart filling pressures in patients at increased risk.
2型糖尿病（T2D）患者舒张功能障碍和射血分数保留的心力衰竭（HFpEF）患病率较高，这反过来又导致住院和死亡风险增加。然而，导致左心室充盈压升高的危险因素及其相对重要性仍存在争议。我们试图阐明高危T2D患者中广泛的有创和无创危险因素与心脏充盈压之间的关联。
本研究前瞻性纳入心血管事件高危的T2D患者。对参与者进行全面的表型分析，包括静息和运动时的右心导管检查、超声心动图、尿白蛋白排泄量（UACR），以及使用心脏Rb-PET/CT对其心肌血流速率（MFR）进行定量分析。在纳入研究的37例患者中，22例（59%）符合HFpEF的有创标准。在39个变量中，只有2个变量被确定为与静息时通过肺毛细血管楔压（PCWP）评估的左心室充盈压相关的独立因素；高血压病史（系数：2.6 mmHg [0.3；5.0]，P = 0.030）和MFR（P = 0.026）。我们发现MFR与PCWP之间存在显著的负相关，MFR每整数变化时，PCWP的系数为-2.3 mmHg（-4.3；-0.3）。在我们的研究中，MFR范围为1.18至3.68，这对应于MFR最低与最高的患者之间PCWP相差约6 mmHg。在运动期间，只有2个变量被确定为与PCWP相关的临界独立因素：心肌血流储备（系数：-4.4 [-9.6；0.8]，P = 0.091）和使用β受体阻滞剂（系数：6.1 [-0.1；12.4]，P = 0.053）。
在无已知HFpEF但有心血管疾病危险因素的2型糖尿病患者中，心肌血流速率在左心充盈压从正常到异常的范围内均与静息时的PCWP独立相关。MFR最低与最高的患者之间，PWCP临床上有6 mmHg的显著差异可归因于MFR的差异。这表明，减轻微血管功能障碍的策略可能会减缓高危患者左心室左心充盈压升高的进展。
