Atrial Dysfunction in Significant Atrial Functional Mitral Regurgitation: Phenotypes and Prognostic Implications.

BACKGROUND: Atrial functional mitral regurgitation (AFMR) is associated with increased morbidity and mortality. Left atrial (LA) size and function in AFMR are poorly characterized. We aimed to assess LA function by reservoir strain (LASr) and estimated reservoir work (LAWr) and their impact on outcome in AFMR. METHODS: Consecutive patients at our institution between 2001 and 2019 and with significant (moderate or greater) AFMR were examined. LAWr was estimated as LASr×LA reservoir volume, and patients were grouped by median LASr and LAWr. Outcomes were all-cause death or heart failure hospitalizations. RESULTS: Five hundred fifteen AFMR patients were followed up for 5 (1-17) years. Patients had previously documented atrial fibrillation (AF; 37%), heart failure with preserved ejection fraction (HFpEF) without AF (24%), or both (HFpEF+AF, 39%). LA volume was largest in AF, while LA function parameters were most impaired in the combined HFpEF+AF group. During follow-up, patients with low LASr or LAWr had higher risk of death (P<0.001) and heart failure hospitalization (P<0.05). In Cox regression analyses, low LASr and LAWr, but not LA volume or left ventricular function, were associated with a higher risk of death (LASr: hazard ratio, 2.3 [95% CI, 1.6-3.5]; LAWr: hazard ratio, 3.4 [95% CI, 2.4-4.9]; both P<0.001) after adjustment for clinical and echocardiographic confounders. Low LASr and LAWr were strongest associated with death in HFpEF and HFpEF+AF. CONCLUSIONS: LA reservoir function but not LA size is a robust predictor of outcome in significant AFMR. This provides mechanistic insights into the interplay of functional versus geometric LA changes in AFMR.

Abnormal Mechanics Relate to Myocardial Fibrosis and Ventricular Arrhythmias in Patients With Mitral Valve Prolapse.

BACKGROUND: The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia. METHODS: We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation). RESULTS: Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis (P<0.001). An abnormal strain pattern with distinct peaks pre-end-systole and post-end-systole in inferior-lateral wall was frequent in patients with fibrosis (81 versus 26%, P<0.001) but absent in patients without MVP with basal inferior-lateral wall fibrosis (n=20). During median follow-up of 1008 days, 36 of 87 patients with MVP with >6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis. CONCLUSIONS: Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.

Relation of Increasing QRS Duration Over Time and Cardiovascular Events in Outpatients With Heart Failure.

An increase in the duration of the QRS complex over time has been shown to be associated with poor clinical outcomes in specific subgroups of heart failure (HF) patients. There is a paucity of data on the clinical impact of increasing QRS duration on outcomes in HF with narrow QRS duration. This was a retrospective study of consecutive adult referrals to a tertiary outpatient HF clinic over a 2-year period. All patients with a narrow QRS, (<130 ms) were included. The primary outcome was mortality. Secondary outcomes were HF hospitalization and a composite of HF hospitalization, implantation of cardiac resynchronization therapy or left ventricular assist device and cardiac transplant. A total of 253 patients with 2 or more QRS measurments were included. Death occurred in 41 patients (16%), 258 HF hospitalizations occurred in 116 patients (46%) and the composite occurred in 127 patients (50%). Multivariable analyses found that a rate of QRS duration change of ≥1 ms/month was independently associated with increased mortality (odds ratio [OR] 2.26, 95% confidence interval [CI] 1.04 to 4.91), HF hospitalization (relative risk [RR] 2.01, 95% CI 1.37 to 2.94), and the composite (OR 2.40, 95%CI 1.44 to 4.02). A new QRS >130 ms was also independently associated with mortality (OR 3.27, 95%CI 1.29-8.32), HF hospitalization (RR 2.75, 95% CI 1.72 to 4.4) and the composite (OR 2.52, 95%CI 1.27 to 4.99). In conclusion, in patients with HF and a narrow baseline QRS, an increase in QRS duration of ≥1 ms per month is associated with increased mortality and HF hospitalization. HF patients may benefit from serial monitoring of QRS duration.

Pulmonary Arterial Hypertension Specific Therapy in Patients with Combined Post- and Precapillary Pulmonary Hypertension.

BACKGROUND: Specific therapy for patients with PAH is associated with good outcomes. Little is known about the effect of this treatment in patients with Cpc-PH (PAPm ≥ 25 mmHg, PAWP > 15 mmHg, DPG ≥ 7 mmHg, and/or PVR > 3 WU). This study evaluates the outcome of treating patients with Cpc-PH using PAH specific therapy. METHODS: The primary outcome was survival. Secondary outcomes were WHO functional class and 6-minute walk distance (6-MWD). RESULTS: Twenty-six patients with Cpc-PH (half with VHD and half with HF) received PAHST. Six patients did not tolerate treatment due to pulmonary edema. No predictors for treatment intolerance were identified. In twenty patients who tolerated the treatment, the mean WHO functional class improved from 2.70 ± 0.21 at initial assessment to 2.22 ± 0.21 (p < 0.04) and 2.06 ± 0.21 (p < 0.03) at 6 and 9 months, respectively. Mean 6-MWD improved from 276.0 ± 38.50 meters at initial assessment to 343.9 ± 22.99 meters (p < 0.04) and 364.6 ± 34.85 meters (p = 0.07) at 6 and 9 months, respectively. Twelve patients died during the follow-up period. Mean survival for all patients was 1279.7 ± 193.60 days. CONCLUSION: PAHST may be beneficial in the treatment of Cpc-PH (both short and long term). Prospective randomized controlled trials of PAHST in this population are needed to assess its potential efficacy.