Atrial Mechanics, Atrial Cardiomyopathy and Impact of Atrial Interventions.

Our comprehension of atrial mechanics, atrial cardiomyopathy and their clinical implications across various cardiovascular conditions has advanced significantly. Atrial interventions can have differing effects on atrial mechanics. With the rapid increase in the use of atrial interventions, it is crucial for investigators and clinicians to acknowledge the potential adverse effects of these interventions on atrial mechanics that might not be clinically significant at the time of interventions. Recognizing the preclinical stage of atrial maladaptation might enable early interventions before the development of irreversible atrial remodeling and clinical manifestation. We review normal atrial function and mechanics, and atrial cardiomyopathy in select cardiovascular conditions. We also summarize and discuss the current evidence of the impact of various atrial interventions on atrial function and mechanics.

Mechanical Thrombectomy for High-Risk Pulmonary Embolism: Insights From the US Cohort of the FLASH Registry.

Background: Acute mortality for high-risk, or massive, pulmonary embolism (PE) is almost 30% even when treated using advanced therapies. This analysis assessed the safety and effectiveness of mechanical thrombectomy (MT) for high-risk PE. Methods: The prospective, multicenter FlowTriever All-comer Registry for Patient Safety and Hemodynamics (FLASH) study is designed to evaluate real-world PE patient outcomes after MT with the FlowTriever System (Inari Medical). In this study, acute outcomes through 30 days were evaluated for the subset of patients with high-risk PE as determined by the sites and following European Society of Cardiology guidelines. An independent medical monitor adjudicated adverse events (AEs), including major AEs: device-related mortality, major bleeding, or intraprocedural device-related or procedure-related AEs. Results: Of the 799 patients in the US cohort, 63 (7.9%) were diagnosed with high-risk PE; 30 (47.6%) patients showed a systolic blood pressure <90 mm Hg, 29 (46.0%) required vasopressors, and 4 (6.3%) experienced cardiac arrest. The mean age of patients with high-risk PE was 59.4 ± 15.6 years, and 34 (54.0%) were women. At baseline, 45 (72.6%) patients were tachycardic, 18 (54.5%) showed elevated lactate levels of ≥2.5 mM, and 21 (42.9%) demonstrated depressed cardiac index of <2 L/min/m2. Immediately after MT, heart rate improved to 93.5 ± 17.9 bpm. Twenty-five (42.4%) patients did not require an overnight stay in the intensive care unit, and no mortalities or major AEs occurred through 48 hours. Moreover, no mortalities occurred in 61 (96.8%) patients followed up through the 30-day visit. Conclusions: In this cohort of 63 patients with high-risk PE, MT was safe and effective, with no acute mortalities reported. Further prospective data are needed in this population.

Seated Pulmonary Artery Pressure Monitoring in Patients With Heart Failure: Results of the PROACTIVE-HF Trial.

BACKGROUND: Monitoring supine pulmonary artery pressures to guide heart failure (HF) management has reduced HF hospitalizations in select patients. OBJECTIVES: The purpose of this study was to evaluate the effect of managing seated mean pulmonary artery pressure (mPAP) with the Cordella Pulmonary Artery sensor on outcomes in patients with HF. METHODS: Following GUIDE-HF (Hemodynamic-GUIDEd Management of Heart Failure Trial), with U.S. Food and Drug Administration input, PROACTIVE-HF (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial) was changed from a randomized to a single-arm, open label trial, conducted at 75 centers in the USA and Europe. Eligible patients had chronic HF with NYHA functional class III symptoms, irrespective of the ejection fraction, and recent HF hospitalization and/or elevated natriuretic peptides. The primary effectiveness endpoint at 6 months required the HF hospitalization or all-cause mortality rate to be lower than a performance goal of 0.43 events/patient, established from previous hemodynamic monitoring trials. Primary safety endpoints at 6 months were freedom from device- or system-related complications or pressure sensor failure. RESULTS: Between February 7, 2020, and March 31, 2023, 456 patients were successfully implanted in modified intent-to-treat cohort. The 6-month event rate was 0.15 (95% CI: 0.12-0.20) which was significantly lower than performance goal (0.15 vs 0.43; P < 0.0001). Freedom from device- or system-related complications was 99.2% and freedom from sensor failure was 99.8% through 6 months. CONCLUSIONS: Remote management of seated mPAP is safe and results in a low rate of HF hospitalizations and mortality. These results support the use of seated mPAP monitoring and extend the growing body of evidence that pulmonary artery pressure-guided management improves outcomes in heart failure. (Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial [PROACTIVE-HF]; NCT04089059).

Acute outcomes for the full US cohort of the FLASH mechanical thrombectomy registry in pulmonary embolism.

BACKGROUND: Evidence supporting interventional pulmonary embolism (PE) treatment is needed. AIMS: We aimed to evaluate the acute safety and effectiveness of mechanical thrombectomy for intermediate- and high-risk PE in a large real-world population. METHODS: FLASH is a multicentre, prospective registry enrolling up to 1,000 US and European PE patients treated with mechanical thrombectomy using the FlowTriever System. The primary safety endpoint is a major adverse event composite including device-related death and major bleeding at 48 hours, and intraprocedural adverse events. Acute mortality and 48-hour outcomes are reported. Multivariate regression analysed characteristics associated with pulmonary artery pressure and dyspnoea improvement. RESULTS: Among 800 patients in the full US cohort, 76.7% had intermediate-high risk PE, 7.9% had high-risk PE, and 32.1% had thrombolytic contraindications. Major adverse events occurred in 1.8% of patients. All-cause mortality was 0.3% at 48-hour follow-up and 0.8% at 30-day follow-up, with no device-related deaths. Immediate haemodynamic improvements included a 7.6 mmHg mean drop in mean pulmonary artery pressure (-23.0%; p<0.0001) and a 0.3 L/min/m2 mean increase in cardiac index (18.9%; p<0.0001) in patients with depressed baseline values. Most patients (62.6%) had no overnight intensive care unit stay post-procedure. At 48 hours, the echocardiographic right ventricle/left ventricle ratio decreased from 1.23±0.36 to 0.98±0.31 (p<0.0001 for paired values) and patients with severe dyspnoea decreased from 66.5% to 15.6% (p<0.0001).  Conclusions: Mechanical thrombectomy with the FlowTriever System demonstrates a favourable safety profile, improvements in haemodynamics and functional outcomes, and low 30-day mortality for intermediate- and high-risk PE.

A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study.

OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, California) in a prospective trial of patients with acute intermediate-risk pulmonary embolism (PE). BACKGROUND: Catheter-directed thrombolysis has been shown to improve right ventricular (RV) function in patients with PE. However, catheter-directed thrombolysis increases bleeding risk and many patients with PE have relative and absolute contraindications to thrombolysis. METHODS: Patients with symptomatic, computed tomography-documented PE and RV/left ventricular (LV) ratios ≥0.9 were eligible for enrollment. The primary effectiveness endpoint was core laboratory-assessed change in RV/LV ratio. The primary safety endpoint comprised device-related death, major bleeding, treatment-related clinical deterioration, pulmonary vascular injury, or cardiac injury within 48 h of thrombectomy. RESULTS: From April 2016 to October 2017, 106 patients were treated with the FlowTriever System at 18 U.S. sites. Two patients (1.9%) received adjunctive thrombolytics and were analyzed separately. Mean procedural time was 94 min; mean intensive care unit stay was 1.5 days. Forty-three patients (41.3%) did not require any intensive care unit stay. At 48 h post-procedure, average RV/LV ratio reduction was 0.38 (25.1%; p < 0.0001). Four patients (3.8%) experienced 6 major adverse events, with 1 patient (1.0%) experiencing major bleeding. One patient (1.0%) died, of undiagnosed breast cancer, through 30-day follow-up. CONCLUSIONS: Percutaneous mechanical thrombectomy with the FlowTriever System appears safe and effective in patients with acute intermediate-risk PE, with significant improvement in RV/LV ratio and minimal major bleeding. Potential advantages include immediate thrombus removal, absence of thrombolytic complications, and reduced need for post-procedural critical care.

Experimental model of inappropriate sinus tachycardia: initiation and ablation.

OBJECTIVE: The purpose of the present study was to develop an experimental model of inappropriate sinus tachycardia (IST) by injecting a catecholamine into a fat pad containing autonomic ganglia (AG) innervating the sinus node (SN). METHODS: Initial protocols in 3 groups of pentobarbital anesthetized dogs consisted of (1) slowing the heart rate (HR) by electrical stimulation of AG in the fat pad; (2) the effect of intravenous injection of epinephrine (0.1-0.3 mg) on the HR and systolic blood pressure (BP); (3) the response of SN rate to intravenously injected isoproterenol (1 microgm/kg). These studies established a reference for the response to epinephrine injection (mean dose 0.2 +/- 0.9 mg, n = 14) into the fat pad at the base of the right superior pulmonary vein (RSPV). ECG leads, right atrial and His bundle electrograms, BP and core body temperature were continuously monitored. RESULTS: Epinephrine, injected into the fat pad, caused a significant increase in heart rate (HR, average: 211 +/- 11/min, p < 0.05 compared to control) but little change in systolic BP, 149 +/- 10 mmHg, p = NS (Group I, N = 8). The tachycardia lasted >30 minutes. Ice mapping and P wave morphology showed the tachycardia origin in the SN in 6/8 and in the crista terminalis (CT) in 2. Injection of 0.4 cc of formaldehyde into the FP restored HR (159 +/- 16) toward baseline (154 +/- 18). In Group II (N = 6), the same regimen induced a significant increase in both HR and systolic BP (194 +/- 17/min and 230 +/- 24 mmHg, respectively) compared to control values (143 +/- 23/min, 162 +/- 24 mmHg) which lasted for > 30 minutes. Ice mapping and P wave morphology showed that the pacemaker was in the SN (1), overlying the CT (2), or atrioventricular junction (2). Formaldehyde (0.4 cc) injected into the FP restored both HR and systolic BP toward baseline values (148 +/- 29/min and 152 +/- 24 mmHg, p = NS) and prevented, slowing of the HR by electrical stimulation of the AG; moreover, the same dose of epinephrine injected intravenously increased HR and SBP but only for 2-5 minutes; Isoproterenol (1 microg/kg) injected intravenously induced essentially the same increase in sinus rate after AG ablation as in the control state (194 +/- 15/min vs 193 +/- 23/min, p = NS). CONCLUSION: Experimental IST is mainly localized in the SN or CT. Ablation of the AG terminates IST without impairing the SN response to an adrenergic challenge.

Hypertension and cardiac failure in its various forms.

Hypertension clearly increases the risk of systolic or diastolic heart failure. With aging population and advancements in treatment of cardiovascular diseases, the prevalence of heart failure is ever-increasing and is a principal cause of cardiovascular morbidity and mortality. Treating hypertension has been shown to decrease the risk of development of heart failure and hence underscores the early recognition and treatment of hypertension and hypertensive heart disease. Antihypertensive treatment with drugs from all classes except direct vasodilators is effective in reversing LVH and preventing heart failure. Also, all of the major classes of antihypertensive drugs, particularly beta-blockers and RAS antagonists, with the exception of calcium antagonists, have been shown to improve survival in patients who have LV systolic dysfunction. However, phenotyping and identifying the pathophysiology and appropriate treatments for patients who have diastolic dysfunction and heart failure with preserved ejection fraction has been a daunting task. At this time, treatment of these patients is largely empiric, focusing on BP control, and treating or avoiding intravascular volume overload.

Usefulness of heart rate as an independent predictor for survival after heart transplantation.

It was unclear whether increased heart rate (HR) increased long-term mortality after heart transplantation (HT). The aim of this study was to evaluate whether HR predicted survival after HT. A retrospective analysis of patients who underwent HT at our institution was performed. Ethnicity, gender, date of birth, age at transplantation, length of follow-up after transplantation, cardiac rhythm within 3 months after transplantation, age at death, reason for transplantation, cause of death, and baseline medications after transplantation were recorded. Continuous variables, such as HR, blood pressure, cardiac ejection fraction, presence of allograft vasculopathy, and serum creatinine, were recorded at <3 months, 6 months, and 1 year after HT, then annually to 10 years after HT. Seventy-eight patients with a mean age of 50 +/- 13 years were identified. Mean survival was 8.5 +/- 6.5 years. Of 78 patients, 32 patients had an HR 90 beats/min within 3 months after HT. There was a mean decrease in HR of 6 beats/min during 10 years (p <0.03). Multivariate survival analysis showed that HR >90 beats/min was a significant predictor of early mortality (hazard ratio 2.8, 95% confidence interval 1.5 to 5.1, p <0.0013). Patients with a net increase in HR during 10 years had an increased risk of death compared with patients with no change or a net decrease in HR (hazard ratio 4.7, 95% confidence interval 1.9 to 12.0, p <0.002). No significant differences in cause of death between patients with an HR 90 beats/min existed. In conclusion, HT patients with an HR >90 beats/min within the first 3 months after HT were 2.8 times more likely to die than patients with an HR