TAPSE/sPAP prognostic value for In-Hospital Adverse Events in Patients Hospitalized for Acute Coronary Syndrome.

AIMS: Although several studies have shown that the right ventricular to pulmonary artery (RV-PA) coupling, assessed by the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) using echocardiography, is strongly associated with cardiovascular events, its prognostic value is not established in acute coronary syndrome (ACS). We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for ACS in a retrospective analysis from the prospective ADDICT-ICCU study. METHODS AND RESULTS: 481 consecutive patients hospitalized in intensive cardiac care unit (mean age 65±13 years, 73% of male, 46% STEMI) for ACS (either ST-elevation [STEMI] or non-ST-elevation [NSTEMI] myocardial infarction) with TAPSE/sPAP available were included in this prospective French multicentric study (39 centers). The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 33 (7%) patients. ROC-curve analysis identified 0.55 mm/mmHg as the best TAPSE/sPAP cut-off to predict in-hospital MACEs. TAPSE/sPAP <0.55 was associated with in-hospital MACEs, even after adjustment with comorbidities (OR:19.1, 95%CI[7.78-54.8]), clinical severity including left ventricular ejection fraction (OR:14.4, 95%CI[5.70-41.7]) and propensity-matched population analysis (OR:22.8, 95%CI[7.83-97.2], all p<0.001). After adjustment, TAPSE/sPAP <0.55 showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.16; global chi-square improvement: 52.8; LR-test p<0.001) with similar results for both STEMI and NSTEMI subgroups. CONCLUSION: A low RV-PA coupling defined as TAPSE/sPAP ratio <0.55 was independently associated with in-hospital MACEs and provided incremental prognostic value over traditional prognosticators in patients hospitalized for ACS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

In-hospital prognosis of acute ST-elevation myocardial infarction in patients with recent recreational drug use.

AIMS: Although recreational drug use may induce ST-elevated myocardial infarction (STEMI), its prevalence in patients hospitalized in intensive cardiac care units (ICCUs), as well as its short-term cardiovascular consequences, remains unknown. We aimed to assess the in-hospital prognosis of STEMI in patients with recreational drug use from the ADDICT-ICCU study. METHODS AND RESULTS: From 7-22 April 2021, recreational drug use was detected prospectively by a systematic urine multidrug test in all consecutive patients admitted for STEMI in 39 ICCUs across France. The primary endpoint was major adverse cardiac events (MACEs) defined by death, resuscitated cardiac arrest, or cardiogenic shock. Among the 325 patients (age 62 ± 13 years, 79% men), 41 (12.6%) had a positive multidrug test (cannabis: 11.1%, opioids: 4.6%, cocaine: 1.2%, 3,4-methylenedioxymethamphetamine: 0.6%). The prevalence increased to 34.0% in patients under 50 years of age. Recreational drug users were more frequently men (93% vs. 77%, p = 0.02), younger (50 ± 12 years vs. 63 ± 13 years, P < 0.001), and more active smokers (78% vs. 34%, P < 0.001). During hospitalization, 17 MACEs occurred (5.2%), including 6 deaths (1.8%), 10 cardiogenic shocks (3.1%), and 7 resuscitated cardiac arrests (2.2%). Major adverse cardiac events (17.1% vs. 3.5%, P < 0.001) and ventricular arrhythmia (9.8% vs. 1.4%, P = 0.01) were more frequent in recreational drug users. Use of recreational drugs was associated with more MACEs after adjustment for comorbidities (odds ratio = 13.1; 95% confidence interval: 3.4-54.6). CONCLUSION: In patients with STEMI, recreational drug use is prevalent, especially in patients under 50 years of age, and is independently associated with an increase of MACEs with more ventricular arrhythmia. TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT05063097.

The ventilatory component of the muscle metaboreflex is overstimulated in transthyretin cardiac amyloidosis patients with poor aerobic capacity.

Background: The exercise pressor reflex, i.e., metabo- and mechano-reflex, partially regulates the control of ventilation and cardiovascular function during exercise. Abnormal exercise pressor reflex response has been associated with exaggerated ventilatory drive, sympathovagal imbalance and exercise limitation in chronic heart failure patients. Whether metaboreflex is over-activated and participate to poor aerobic capacity in patients with hereditary transthyretin cardiac amyloidosis (CA-TTR) is unknown. Methods: Twenty-two CA-TTR patients (aged 76 ± 7, 68% male) with the V122I (p.Val142Ile) transthyretin underwent a thorough evaluation including heart rate variability metrics, electrochemical skin conductance (ESC), physical function cardiopulmonary exercise testing, and muscle metaboreflex assessment. Eleven control subjects were chosen for muscle metaboreflex assessment. Results: Age-matched controls (n = 11) and CA-TTR patients (n = 22) had similar metaboreflex sensitivity for heart rate, stroke volume, cardiac index and mean systemic arterial pressure. Compared with age-matched controls, metaboreflex sensitivity for systemic vascular resistance (-18.64% ± 6.91% vs 3.14% ± 23.35%) and minute-ventilation responses (-9.65% ± 14.83% vs 11.84% ± 23.1%) was markedly increased in CA-TTR patients. Values of ESC displayed positive correlations with stroke volume (r = 0.53, p = 0.011) and cardiac index (r = 0.51, p = 0.015) components of metaboreflex sensitivity, an inverse correlation with systemic vascular resistance (r = -0.55, p = 0.008) and a trend with mean arterial (r = -0.42, p = 0.052) components of metaboreflex sensitivity. Peak aerobic capacity (peak VO2%) displayed an inverse correlation with the ventilation component of metaboreflex sensitivity (r = -0.62, p = 0.015). Conclusion: Consistent with the "muscle hypothesis" in heart failure, it is proposed that deterioration of skeletal muscle function in hereditary CA-TTR patients may activate muscle metaboreflex, leading to an increase in ventilation and sensation of breathlessness, the perception of fatigue, and overall sympathetic activation.

Determinants of ventilatory inefficiency in transthyretin cardiac amyloidosis: The role of excessive ventilatory drive.

Background and objective: Along with impaired aerobic capacity, increased slope of the relationship between ventilation (VE) and pulmonary CO2 output (VCO2), i.e., VE-VCO2 slope is a common finding in patients with cardiac amyloidosis (CA), which suggests ventilatory inefficiency. Little is known about mechanisms leading to ventilatory inefficiency in CA patients. The purpose of this investigation was to examine the factors that underlie the abnormal ventilatory efficiency in transthyretin hereditary CA patients, such as excessive ventilatory drive, inability of pulmonary blood flow to increase adequately during exercise and excessive sympathetic stimulation, which are known mechanisms of VE-VCO2 slope increase. Methods: In this single-center retrospective observational study, consecutive patients (n = 41) with known familial transthyretin amyloidosis p.Val142Ile mutation carriers with confirmed cardiac phenotype were included. Results: Compared with CA patients without ventilatory inefficiency (VE-VCO2 slope < 36), patients with ventilatory inefficiency (VE-VCO2 slope ≥ 36) had increased inter-ventricular septum thickness, lower VO2 peak along with hyperventilation, and prolonged post-exercise heart rate recovery. By multivariate analysis, only excess of minute-ventilation at anaerobic threshold (ß = 0.127; p = 0.011) remained an independent predictor of ventilatory inefficiency. Conclusion: Our data suggest that high ventilatory stimulation during exercise leading to hyperventilation is the main determinant of ventilatory inefficiency in hereditary transthyretin cardiac amyloidosis patients. This novel finding helps to better understand the mechanism of exercise intolerance in these patients where physiological limitation may be related to both heart dysfunction and abnormal pulmonary response.